A Unique Model to Accelerate Industry-sponsored Research in Malaysia – Journal for Clinical Studies

The influx of industry-sponsored research (ISR) into the Asia Pacific region is continually growing due to the rising costs and complicated processes involved in drug development. Several countries within the region such as Singapore and, more notably, South Korea, have taken the initiative to develop and further strengthen their place as preferred destinations to conduct clinical trials. One such initiative is the establishment of specific entities that focus on nurturing and expanding the existing clinical trial ecosystem within the individual countries. With over 20 years of experience in conducting late-phase trials, the Malaysian government is no exception.

In the last six years, Malaysia has been steadily building a comprehensive and supportive clinical research ecosystem within the country. This includes the creation of Clinical Research Malaysia (CRM), a non-profit company wholly owned by the Ministry of Health (MOH).1 This review will present CRM as a unique business model, established to create a thriving and comprehensive ecosystem for ISRs in Malaysia and how this business model may be relevant and replicated in Asian countries that are looking to focus on attracting ISRs.

Clinical Research Malaysia –
Addressing the Need for a Unique Business Model
Previously, sponsors and CROs have found it challenging in understanding the requirements, processes and systems involved in conducting ISRs in Malaysia. As a result, the time taken for them to bring in a clinical trial would have been prolonged. As Malaysia gears itself to increase the volume of ISRs into the country, the government is continually taking steps to develop its clinical research ecosystem. To this end, developing mechanisms to ensure that these studies are performed and managed efficiently from its inception has been a main focus. One such example is a “centralised support service”1 that should facilitate the business and administrative aspects of clinical trials.2

Tang et al. determined that a focused research infrastructure is able to facilitate rapid development of trials (faster trial progress from institutional review board (IRE) approval to activation by 1.1 months and from activation to first enrolment by 0.3 months in ISRs) as well increased patient accrual rates.3 Though the infrastructure studied focuses on oncology trials, some of its components such as a “capitalist” research model, enrolling patients from early-phase trials into subsequent later-phase trials, parallel processing for trial approval and a decentralised staffing model can be extended to government and research institutions to cultivate a thriving clinical trial ecosystem.

In the Asia Pacific region, other countries have also established similar entities to further advance their clinical research industry. Two examples are the formation of the South Korea National Enterprise for Clinical Trials (KoNECT) and Singapore Clinical Research Institute (SCRI). KoNECT was established to nurture the country’s clinical trial infrastructure and capabilities4 while SCRI is dedicated to enhancing the standards of clinical research capabilities in Singapore.

Creation of CRM
Acknowledging the significant growth of the drug development industry, the Malaysian government ensured the National Key Economic Area (NKEA) encompassing the healthcare industry included the creation of a supportive ecosystem to grow clinical research.1 Its focus is to allow for the conduct of more efficient and higher quality trials by increasing the number of clinical research centres, developing a larger pool of certified investigators and improving approval timelines.5 Therefore, CRM was established in 2012 to effectively increase the speed, reliability and delivery of outcomes for all stakeholders involved in clinical research. Its vision is to highlight Malaysia as a preferred global destination for clinical research by improving the local ecosystem to support the growth of ISRs within the country.1 As a non-profit company that is wholly owned by the Malaysian MOH, it is governed by a board of directors that include the Minister and Secretary General of the MOH, the Director of the National Clinical Research Centres and representatives from the Pharmaceutical Association of Malaysia and university hospitals. The management team of CRM follows that of a corporate entity headed by a CEO and senior leadership team comprising finance, human resources, business development and clinical operations.

Challenges Within the Malaysian
Clinical Trial Ecosystem Prior to CRM
Before the establishment of CRM, the country faced several challenges that dampened the conduct of ISRs. These included long-drawn-out hiring and asset acquisition processes that involved complicated and fractionated government bureaucracy, poor transparency of funds management and a lack of activities to increase the number of talented and trained human resource, as well as adequately set-up trial investigation sites. There was also no clear research pathway to develop the potential interests of existing investigators and support staff, and a need to ensure that the pool of experienced principal investigators (Pls) was maintained through proper succession plans. Further, there was a need to manage the whole national clinical research ecosystem under one centralised body. This entails collaborating with various stakeholders within the clinical research ecosystem, such as sponsors and contract research organisations (CROs), private and public doctors from universities, health clinics and hospitals, as well as the regulatory agencies and ethics committees, under a single point of contact to facilitate the processes of end-to-end activities involved in conducting ISRs.1

CRM as a Unique Working Model
The detailed objectives of CRM as discussed in a prior article1 are to locally improve capabilities at trial sites and of human resource required to run trials which conforms to international quality and standards, establishing high quality feasibility assessments and investigator selection mechanisms and ensuring speedy and transparent administrative processes, especially in the management of the clinical trial budget.

CRM is also tasked to initiate and grow collaborations locally and internationally to bring in investments by global pharmaceutical and CRO companies and address the lack of awareness of and interest in clinical research among the healthcare fraternity and the public.

As a whole, the objectives of CRM are to leverage Malaysia’s distinct advantages such as its diverse and large clinical trial-na’ive population, its low clinical trial density,6 low health costs6 and competitive approval timelines compared to its counterparts in Asia. Part of its objectives is to also develop the existing infrastructure for the country’s clinical research centre (CRC) network, which is an extensive network of research centres, housed within various MOH hospitals.7

There are five pillars that constitute CRM’s strategies toward accomplishing its objectives. These are to grow the numbers of PIs and sites conducting ISRs, to increase the volume of ISRs, collaborate with stakeholders, create awareness of CRM and develop human capital. Overall, the strategies allow CRM to centralise the management and optimise and mobilise resources quickly and efficiently.

Being an entity under the MOH facilitates CRM’s initiatives and activities with private healthcare facilities, regulatory agencies such as the National Pharmaceutical Regulatory Agency (NPRA), which is its main stakeholder, and ethics committees. It also gives CRM access to the large CRC networks and its investigator database, the Medical Research Ethics Committee (MREC), the Medical Device Authority (MDA) and various other MOH components. Through its government affiliations, CRM is able to work with university hospitals and their individual institutional review boards (IRBs), the Malaysian Investment Development Authority (MIDA) and other important government agencies that have roles in developing a healthy clinical trial ecosystem within the country.

Complimentary Feasibility Studies
In an effort to attract global sponsors and CROs into Malaysia, CRM offers a range of services to support and facilitate their needs in conducting ISRs. One of the key core services that CRM offers is providing feasibility studies and investigator matching at no cost to sponsors and CROs. A clinical trial feasibility is a process of evaluating the possibility of conducting a particular clinical trial in a particular geographical region with an objective of running a trial at an optimum timeline, cost and patient accrual rates. The centralised feasibility service by CRM functions as a single point of contact for sponsors and CROs. It capitalises on a comprehensive updated internal database of investigators, enables outreach to a wider range of investigators and sites, and leads to streamlined communications, which reduces delay and confusion on the ground.

Prior to having a centralised feasibility management service in Malaysia, sponsors and CROs had to conduct feasibility assessments individually by relying on their own internal databases, which are based on their company’s experiences with previous feasibility studies.8 Additionally, due to the dynamic nature of Malaysia’s research ecosystem, these individual databases have led to inaccuracies, which have misguided and delayed feasibility approaches. Examples of the dynamic changes are movements (e.g. promotions, transfers or retirements) of investigators within the healthcare setting, changes in regulatory environment, site staffing or person in charge, and resources leading to change in site capabilities.

A centralised feasibility service, on the other hand, allows for a single point of contact that capitalises on CRM presence in all 33 major clinical research centres nationwide, which enables it to have a comprehensive database that is frequently updated, which ultimately reduces delay for ISRs initiation (Figure 1).

On a nationwide perspective, a centrally managed feasibility structure is an attractive alternative to sponsors and CROs looking to enhance efficiency and width of a feasibility outreach, avoid redundant processes and promote a more accurate assessment of Malaysia’s capabilities.

Consultation and Management of Clinical Trial Budget
CRM is authorised by the Malaysian government to act as a trustee in managing the budgets of clinical trials conducted in the country by receiving and executing its disbursement. It ensures that payments are made to the relevant parties involved in the conduct of clinical trials and that they are made in a fair and transparent manner. The majority of investigators conducting clinical trials are in the government sector, and according to the General Orders of the Malaysian Government,9 investigators who are government officers shall not receive money paid directly to them (from sponsors/CROs) derived from their clinical trial activities. In light of this, CRM legitimises the transfer of the trial funds by managing the trial budget and channelling the investigators’ fees to the relevant investigators.

Placement of Study Coordinators
CRM recruits and provides training for its study coordinators (SCs) who are then placed at trial sites nationwide to assist investigators with ISRs. At the start of 2018, there were about 110 study coordinators. To ensure that these SCs continuously maintain a high standard of professionalism, frequent trainings related to clinical research such as Good Clinical Practice (GCP) refresher courses, protocol deviation workshops and recruitment trainings are conducted for them.

Review of Clinical Trial Agreement and Non-disclosure Agreement
CRM also assists investigators, sponsors and CROs by reviewing and advising on clinical trial agreements (CTAs) and non-disclosure agreements (NDAs). CRM’s experienced legal officers ensure that all agreements made in relation to the conduct of clinical trials in Malaysia comply with the applicable laws, regulations and guidelines of the Malaysian government. This has significantly reduced the duration of the CTA reviewing process from three months to 14 days.1

The outcomes of bringing together the various touch points involved in ISRs speak to the success of CRM’s unique model. In financial terms, the investment value cumulatively from CRM’s inception in 2012 to 2017 has reached more than RM240 million, which is 42% of its 2020 target.

Between 2014 and 2017, there was more than 400% growth in sponsors and more than 200% growth in CROs that have utilised CRM’s services (Figure 2). By the end of 2017, there were 1110 new and ongoing ISRs and more than 1900 skilled jobs (versus the 1000 set) created in the clinical research industry before the projected 2020 timeline. These numbers far surpass the KPI set for CRM.10

The reported number of full feasibilities received by CRM from sponsors and CROs showed an increasing trend from 2014 to 2017 with more than a twofold growth (Figure 3). Besides offering this service on a complimentary basis, sponsors and CROs have also recognised CRM’s capability and timeliness in reverting a feasibility assessment and have therefore approached CRM in most of their enquiries.

Compared to the current standard working model of ISRs wherein individual sponsors and CROs attempt to conduct clinical trials without a centralised organisation, CRM offers a new paradigm as well as value proposition. The uniqueness of CRM is that it forms an overarching collaborative force between all the different stakeholders involved in the clinical trial ecosystem – sponsors, CROs, government bodies, regulatory agencies, ethics committees, institutional research facilities and private healthcare facilities.

Through its various strategies and activities, the model allows for an integrative approach to transform the ISR industry into a business model with an efficient business management perspective and added dimensions such as marketing and business development, all within a framework that is supported by a country’s legal and ethical framework. As the target year 2020 approaches and as CRM continues to expand and gain experience, it offers a working model that may be replicated in other countries within the region that seek to build an efficient and thriving clinical research ecosystem.


  1. Ooi AJA & Khalid KF. Malaysia’s clinical research ecosystem. Appl Clin Trials. (2017). http://www.appliedclinicaltrialsonline.com/malaysia-s­clinical-research-ecosystem.
  2. Rahman S & Majumder MAA. Managing clinical trials in Asia: issues, threats, oppottunities and approaches. South East Asia J. Public Health (online). 2(2), 80-84 (2012).
  3. Tang C, Hess KR, Sanders D, Davis SE, Buzdar AU, Kurzrock R, Lee JJ, Meric-Bernstam F & Hong DS. Modifying the clinical research infrastructure at a dedicated clinical trials unit: assessment of trial development, activation, and participant accrual. Clin. Cancer Res. 23(6), 1407-1413 (2016).
  4. Chee D, Park MS & Sohn J-H. New initiatives for transforming clinical research in Korea. J Med. Dev. Sci. 1(2), 27-32 (2015). doi:10.18063/JMDS.2015.02.003.
  5. Performance Management and Delivery Unity, Malaysia. Healthcare NKEA fact sheet. http:ff etp.pemandu.gov.my /upload/NKEA_Factsheet_ Healthcare.pdf visited on 30 November 2018.
  6. Frost & Sullivan. Asia: preferred destination for clinical trials. (2016).
  7. Sim A & Astudillo D. Working with Clinical Research Malaysia to move Malaysia forward. Ann. Clin. Lab. Res. 3(333), 1 (2015).
  8. Khalid KF, Ooi AJA & Tay WC. How a centralized feasibility service attracts sponsors and contract research organizations to Malaysia. Presented at Drug Information Association (DIA), Chicago, Illinois (2017).
  9. Government of Malaysia. General Orders Chapter D, Clause 5. (1993).
  10. Clinical Research Malaysia. Annual Report (2017).

Source – Journal for Clinical Studies

Is GCP Refresher Training Effective – Perspective from Malaysia

The International Conference on Harmonization—Good Clinical Practice (ICH-GCP) is an international ethical and scientific quality standard that ensures the rights, safety and well-being of clinical trial subjects are protected and that the clinical trial data generated are credible1.

Malaysia GCP Guideline was developed by National Pharmaceutical Regulatory Agency (NPRA) in 1999. This guideline adopts the basic principles outlined by ICH-GCP with some modifications to adapt to local conditions2The object of the Malaysia GCP Guideline is to ensure that drug-related trials in Malaysia are conducted in accordance with international ethical and scientific standards2. Although there is currently no legislative requirement for GCP training, mechanisms were in placed to ensure that Investigators are trained on GCP. For example, it is mandatory to submit a copy of Principal Investigator’s GCP certificate when obtaining regulatory approval from NPRA to conduct a clinical trial3. In addition, all investigators must submit their GCP certificates for ethics committee’s approval in Malaysia4. Since the first edition of Malaysian GCP to the current 4th edition, approximately 12,000 clinicians have been GCP certified5.

It is recommended for GCP certified personnel to be retrained on GCP guidelines every three years in order to stay up to date with updated regulations, standards, and guidelines6. With this, Clinical Research Malaysia (CRM), a research organization founded by Malaysia Ministry of Health (MOH), has taken the initiative to conduct GCP Refresher Workshop for clinicians, nurses, allied health professionals and study coordinators who have been certified with Malaysian GCP. The objective of the workshop was to provide a review on the principles of GCP, to improve participants’ skills and knowledge on managing the conduct of a clinical trial as well as to share recommendations on how to conduct a GCP-compliant clinical trial.

Since the first workshop in 4 October 2016, CRM has conducted 31 GCP refresher workshops throughout Malaysia to approximately 450 participants at no cost. Majority of the participants are clinicians, nurses, allied health professionals from government hospitals who are involved in clinical trials. Over the course of the conduct of the workshop, modifications have been made based on participants’ feedback to improve the quality and the learning outcome of the workshop. A summary of the changes in the workshop agenda is listed in Table 1.

Table 1: Changes in presented topics from 2016 to present

As shown in Table 1, pre- and post-workshop assessment test was introduced in 16 March 2017 in order to evaluate the effectiveness of the workshop on participants’ knowledge on GCP.

In this paper, we analyzed the pre- and post-workshop assessment scores for workshops conducted since 16 March 2017.


Before the start of the workshop, participants were required to complete 20 multiple-choice GCP-related questions (pre-workshop assessment). The questionnaires were then collected before the start of the workshop. After the workshop, participants are then required to complete the same set of questions (post-workshop assessment). Participants were given 30 minutes to complete the questionnaire.

The average score of the pre- and post-assessment results from participants of the same workshop will then be calculated. This will constitute one set of data point.

The average score of pre- and post-workshop assessment from each workshop conducted since the introduction of the assessment in 16 March 2017 were compiled. Of the 28 workshops conducted since then, 5 workshops’ data could not be retrieved, hence only 23 sets of data points were analyzed.

The compiled average score of pre- and post-workshop were then compared using Microsoft Excel’s t-test assuming unequal variance to evaluate if there is any significant improvement in the average assessment score after the workshop.


Table 2 shows the compiled data from 23 workshops. 420 participants completed the pre-workshop assessment, and 434 participants completed the post-workshop assessment. There is on average, 20% improvement in the assessment score before and after the workshop.

Table 2: Compilation of the average pre- and post-workshop assessment score.

Table 3: Result of T-test assuming unequal variances comparing the pre- and post-workshop average scores.

As shown in Table 3, the p-value is less than 0.05, suggesting that there the improvement in the score is significant after participants attended the GCP Refresher Workshop.


Training of investigators and allied health professions involved in clinical trials on the regulations and standards that govern clinical trials is important to improve the quality of studies and ensure maximum safety for the study subjects. A survey amongst clinical researchers in Saudi Arabia on their ICH-GCP knowledge found that is poor understanding of investigator’s responsibilities on informed consent, and prompt reporting to the ethics committee7. Hence, refreshing investigators’ awareness of their responsibilities could help to improves the performance of investigators in conducting clinical trials particularly in these important ethical aspects.

The GCP refresher workshop conducted by CRM fulfills its objective to provide revision of the principles of GCP to participants, with more an average of 20% improvement in assessment score after the workshop.

The factors that potentially contribute to the success of the CRM GCP Refresher workshop in improving participant’s score was discussed below:

Case studies discussion

Case studies were included for “Informed Consent”, “Adverse Event Reporting” and “Protocol Deviations” for discussion. Participants were given real-life scenario case studies and they were required to answer guided questions in groups. Study have shown that case studies are more effective than textbook reading at promoting learning of key concepts and comprehension of the relevance of concepts to real life scenario8.

Interactive workshop

Several methods were used to make the workshop interactive such as games, quizzes, videos, group activities and group discussion. Active engagement of participants helps in the retain of information9.

Trainers would also actively engage participants by asking questions and encouraging participants to share their experience and practices. Regulations of clinical research can be understood more easily when participants can reflect the principles upon their own experience10.

Feedback from participants

Participants were given evaluation form at the end of the workshop to provide their feedback and opinion of the workshop. Based on their feedback, modifications were made to improve the conduct of the workshop:

  1. Duration of workshop
    The first GCP Refresher Workshop is a half-day (4 hours) workshop. Participants reflected that the workshop felt rushed and suggested to make it a full-day course. Subsequent workshops were then conducted one full day (8 hours) to ensure participants can learn at a better pace, contributing a better learning outcome.
  2. Content of workshop
    One of the earlier feed-back received is to include more activities especially for safety reporting and protocol deviations. Modifications based on this feedback is the shift from a lecture-style workshop to activity-based workshop. Presentation slides were also revised to be more concise to retain attention.
  3. Provision of GCP booklet
    Following a feedback from participants, the current edition of the Malaysian GCP Guideline booklets were provided for participants to refer to during the workshop.


It is important for investigators and allied health professions who are involved in clinical study to be trained on the latest GCP guideline. GCP Refresher Workshop conducted by CRM is effective in refreshing participants’ knowledge on GCP guideline. The success of the workshop could be attributed to providing case studies for discussion, interactive activities as well as taking participants’ feedbacks into consideration. We would recommend other governing bodies to support the conduct of similar interactive workshops in their jurisdiction; and to take participants’ feedback for continuous improvement.

Yoong Kai Shen is the Senior Training Executive, and Joanne Yeoh is the Head of Clinical Operations, both of Clinical Research Malaysia.


  1. Good Clinical Practice Network, n.d. ICH GCP Good Clinical Practice. Retrieved 05Nov2019 from: https://ichgcp.net/
  2. National Pharmaceutical Regulatory Agency, 2018. Malaysian Guideline for Good Clinical Practice 4th Edition. Introduction to Malaysian Guidelines For GCP, Page 8.
  3. National Pharmaceutical Regulatory Agency, 2017. Malaysian Guideline for Application of Clinical Trial Import Licence and Clinical Trial Exemption. Retrieved 05Nov2019 from: http://www.nccr.gov.my/view_file.cfm?fileid=33
  4. Society Of Clinical Research Professionals Malaysia, 2016. A Guide to Conducting Clinical Trials in Malaysia, First Edition. Retrieved 05Nov2019 from: http://www.clinicalresearch.my/wp-content/uploads/2017/03/A-Guide-to-Conduct-Clinical-Trials-in-Malaysia.pdf
  5. National Pharmaceutical Regulatory Agency, 2018. Malaysian Guideline for Good Clinical Practice 4th Edition. Forward to the Fourth Edition, Page 4.
  6. National Institutes of Health, n.d. Good Clinical Practice Training. Retrieved 05Nov2019 from: https://grants.nih.gov/policy/clinical-trials/good-clinical-training.htm
  7. Al-Nomay NS, 2015. Compliance with ICH-GCP Guidelines among the Saudi Health Care Professionals: Should Saudi Arabia Conduct Widespread ICH-GCP Training? J Public Health Dev Ctries. 2015; 1(2): 75-82. Retrieved 05Nov2019 from: https://pdfs.semanticscholar.org/0112/2b2e7c0fdd762172251e807c273fcb4a399a.pdf?_ga=2.112527492.1640531090.1574928919-1845614418.1571207552
  8. Bonney KM, 2015. Case study teaching method improves student performance and perceptions of learning gains. J Microbiol Biol Educ. 2015;16(1):21–28. Retrieved 05Nov2019 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416499/
  9. Robin L. Bachelor Patrick M. Vaughan Connie M. Wall, 2012. Exploring the Effects of Active Learning on Retaining Essential Concepts in Secondary and Junior High Classrooms. Retrieved 05Nov2019 from: https://files.eric.ed.gov/fulltext/ED531546.pdf
  10. Halkoaho A, Matveinen M, Leinonen V, Luoto K, Keränen T., 2013. Education of research ethics for clinical investigators with Moodle tool. BMC Med Ethics. 2013;14:53. Published 2013 Dec 12. Retrieved 05Nov2019 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867673/

Source : Applied Clinical Trails Online

Attracting Clinical Research to Malaysia with a Centralized Feasibility Platform

A feasibility study is a crucial part of the clinical trial planning process. It enables sponsors and contract research organizations (CROs) to identify relevant clinicians who may be interested in a particular study.1-4 It also provides information on a site’s infrastructure, human resources and pool of eligible patients.1-4 Such information would help these companies strategize to meet timeliness, sample size requirements and regulatory and ethical conditions, as well as plan for potential challenges.

As clinical research involves multiple stakeholders, the presence of a single point of contact can improve communication, simplify processes, and reduce delays.5,6 This centralized approach is particularly useful for feasibility and site selection processes.6 In Malaysia, Clinical Research Malaysia (CRM), a not-for-profit government-owned organization established in 2012 to nurture an ecosystem that supports industry sponsored research in the country, offers sponsors and CROs a one-stop contact point for feasibility requests, access to the public hospital network of investigators, and other services.

This review will present the role of CRM’s centralized feasibility service in attracting sponsors and CROs to Malaysia.

 The importance of rigorous feasibility studies

Pre-feasibility is information that is collected for preliminary, higher level assessments which allows sponsors and CROs to make decisions at a national and global level. Such enquiries include general questions on standard of care, drug registration status, epidemiology, and estimated patient pool of a particular therapeutic indication. A full feasibility study is a complete documentation of individual sites which may include a confidential disclosure agreement, protocol synopsis and site assessment questionnaire.

About 35% of delays in clinical trials are attributed to patient recruitment with one in five investigators unable to recruit a single patient.4 As non-active or under-performing trial sites can increase the cost of conducting a clinical trial by 20% or more,7 rigorous feasibility studies conducted in multiple centres are recommended.8 But conducting thorough feasibility assessments and selecting appropriate sites may be time consuming, and delay in these preliminary processes will jeopardise study milestones.7 Therefore, if feasibility processes in individual countries can be centralized with a single point of contact for sponsors and CROs, delays and redundancies may be avoided.5,6

Leveraging the strength of a nationwide access to public hospitals

One of the challenges in conducting feasibility studies is maintaining an updated database of principal investigators. The bulk of studies in Malaysia are conducted in government hospitals where doctors are transferred periodically. Therefore, data built on individual company databases can be outdated, thus misguiding and delaying feasibility approaches.

In Malaysia, CRM is the common link for various stakeholders which include sponsors, CROs, private and public doctors from universities, health clinics and hospitals, as well as the regulatory agencies and ethics committees. It is a centralized government-owned body that manages and overlooks Malaysia’s entire clinical research ecosystem.9 The detailed objectives of CRM are discussed in a prior article.10

As a single point of contact for sponsors and CROs and with presence in 33 clinical research centres within public hospitals throughout the country, CRM is vital in streamlining and accelerating feasibility studies in Malaysia.

Evolving to offer complimentary, centralized feasibility management

As CRM receives a variety of enquiries (Table 1) including pre-feasibility and full feasibility requests across all clinical therapeutic areas from both sponsors (pharma, medical device, biotech) and CROs worldwide, the Ministry of Health, Malaysia through CRM, established a centralized feasibility service. This service which is offered complimentary to sponsors and CROs, capitalizes on a comprehensive updated internal database of investigators, and enables outreach to a wider range of investigators and sites.

Previously, the sponsors and CROs conducted their own feasibility assessments and contacted individual sites on their own.11 Separate databases based on a company’s own experience, may not always be updated, and information such as transfer of clinician, changes in site personnel, and regulatory changes may be missed.11

A centralized process leads to centralized knowledge of the research environment which benefits CROs and sponsors engaging the service. A central database which incorporates data on a site’s performance and experience in recruitment and compliance provides more insight into how the site may perform in future trials.1,7 And as a single point of contact, the standardized processes lead to streamlined communications which reduces delay and confusion on the ground. As a result, the turnaround time is shorter than if a sponsor or CRO were to approach individually.

As CRM has a strong network, good rapport with investigators, and is familiar with ground level capacities of sites, poor site selection is less likely. Sites are mapped according to disease to enable the right sites to be approached for a specific patient pool in future. The sites are also mapped to track investigators who were overwhelmed, conducting competing trials, or transferred to ensure that only available investigators are contacted for upcoming trials. Such data would help narrow down the investigators who will give positive responses, thus reducing the time needed for feasibility studies.

When the feasibility team at CRM receives a feasibility questionnaire, a thorough analysis based on CRM’s central intelligence database is done (Figure 1). The questionnaire is then forwarded to relevant investigators. The process from the time CRM is approached to conduct a full feasibility assessment to the time CRM sends the completed questionnaire back to the company would take 5–10 working days. Pre-feasibility enquiries would take between one and five days depending on the complexity of the questions.

In addition, the feasibility specialists help interested potential investigators to address the queries and submit the completed feasibility questionnaire to the enquiring company. They provide technical consultation and organize meetings between investigators and CROs. Information is also compiled when investigators reject feasibility requests to understand their reasons for doing so.

Centralized service, a key attraction for sponsors and CROs 

A centralized feasibility management service is a key attraction for sponsors and CROs,5 as the information from feasibility studies determines the suitability of Malaysia for a particular trial and promotes the capability of the sites to new international companies. The one-stop national feasibility model improves efficiency and timelines, as well as reduces the financial, administrative, and human resource burden of sponsors, CROs and investigators.

Sponsors and CROs are becoming more interested in Malaysia after the introduction of centralized feasibility, with full feasibility requests received by CRM increasing between 2015 and 2018 (Figure 2). There were also a five-fold increase in sponsors and an almost three-fold increase in CROs using CRM’s services in 2018 compared to 2014 (Figure 3). Majority of these companies are international companies (85%).5,11

In addition, feasibility assessments are complimentary, thus contributing to the overall cost-effectiveness of conducting a trial in Malaysia.


Clinical Research Malaysia’s model as a one-stop national center is a primary factor for the expansion in Malaysia’s clinical research industry in the last few years. The growth in sponsors and CROs is made possible through a centralized feasibility team coordinating and overseeing communications with sites. Thus, on a nationwide perspective, a centrally managed feasibility structure is an attractive alternative for sponsors and CROs looking to enhance efficiency and width of a feasibility outreach, avoid redundant processes and promote a more accurate assessment of Malaysia’s capabilities.

Noorzaihan Mat Radi (Senior Feasibility Specialist), Dr. Tan Bee Ying (Feasibility Specialist) and Audrey Ooi (Acting Head of Business Development)  are from Clinical Research Malaysia.


  1. Johnson, O. An Evidence-Based Approach to Conducting Clinical Trial Feasibility Assessments. Clin. Invest. (Lond.). 5(5), 491–499 (2015).
  2. Orsmond, G.I. & Cohn, E.S. The Distinctive Features of a Feasibility Study: Objectives and Guiding Questions. OTJR. (Thorofare N J). 35(3), 169–77 (2015).
  3. Arain, M., Campbell, M.J., Cooper, C.L. & Lancaster, G.A. What is a Pilot or Feasibility Study? A Review of Current Practice and Editorial Policy. BMC. Med. Res. Methodol. 10, 67 (2010).
  4. Rajadhyaksha, V. Conducting Feasibilities in Clinical Trials: An Investment to Ensure a Good Study. Perspect. Clin. Res. 1(3), 106-9 (2010).
  5. Khairul, F.K., Ooi, A.J.A. & Tay, W.C. How a Centralized Feasibility Service Attracts Sponsors and Contract Research Organizations to Malaysia. Poster presented at the 53rd Drug Information Association Annual Meeting, Chicago US: Jun 18–22, 2017.
  6. Arenz, D., Siepmann, T. & Cornely, O.A. Centralized Management of Clinical Trial Feasibility Requests: A Single Center Database Analysis from 2008 to 2015. Clin. Invest. (Lond.). 6(1), 867–874 (2016).
  7. Temkar, P. Accelerating Study Start-Up: The Key to Avoiding Trial Delays. Clinical Researcher, 1 February 2017. Available at https://acrpnet.org/2017/02/01/accelerating-study-start-up-the-key-to-avoiding-trial-delays/, visited on 5 July 2019.
  8. Turner, C.L., Kolias, A.G. & Hutchinson, P.J. Feasibility Studies, Clinical Trials and Multicentre Collaboration. Acta Neurochir. (Wien). 159(1), 11–12 (2017).
  9. Society of Clinical Research Professionals Malaysia. A Guide to Conducting Clinical Trials in Malaysia (1st edition) 2016.
  10. Ooi A.J.A & Khalid K.F. Malaysia’s Clinical Research Ecosystem. Appl. Clin. Trials. 26(4), (2017). Available at http://www.appliedclinicaltrialsonline.com/malaysia-s-clinical-research-ecosystem-0, visited on 5 July 2019.
  11. Ooi, A.J.A & Khairul, F.K. A Unique Model to Accelerate Industry-Sponsored Research in Malaysia.  Journal for Clinical Studies. 11(1), 24–27 (2019).

Source: Journal for Clinical Studies

Ensuring Effective Financial Management in Sponsored Research in Malaysia

The principles of developing, conducting, analysing and subsequently reporting clinical research are widely known.1- 3 However, the success of a clinical trial goes beyond these principles. It also requires a structured, viable and businesslike management of the whole process, without which trials may fail.4 A critical part of managing clinical trials is a solid, well thought out clinical trial budget.5 A successful budget to ensure a good quality clinical trial should not only entail careful detailing of costs that are in line with the trial protocol, but should also include a financial management system that executes this budget in an efficient, timely and transparent manner.

Some issues and challenges in formulating clinical trial budgets could be applicable when managing the finances during conduct of the trials. Examples include how to maintain audit trails and being abreast of billing processes, ensuring all costs have been encountered for, and management of residual monies. Though ultimately the responsibility of the principal investigators, the detailed construction of a clinical trial budget and its management places a huge burden on physicians (or researchers) who have to juggle clinical practice while overseeing the running of multiple clinical trials.

Reducing the Burden of Principal Investigators

Established in 2012, the main objectives of Clinical Research Malaysia (CRM) are to effectively increase the speed, reliability and quality in delivery of outcomes of clinical trials conducted within the country. This is in line with the Malaysian government’s vision to enhance the country’s placing among other clinical trial hubs as a preferred global destination for clinical research.6 CRM, therefore, is also equipped to manage the financial aspects of clinical trials and is currently used extensively by principal investigators, investigators, contract research organisations (CRO) and sponsors conducting clinical trials in Ministry of Health facilities.

CRM’s financial management services extend throughout the trial process, i.e. from prior to study initiation to its close. Legal services are also included during the initial process to support the management of clinical trial agreements (CTAs), parallel with negotiations and refining of the trial budget. CRM reviews and endorses the study budget for the CTA within seven working days (from the last feedback date received from the relevant party involved in the budget negotiation). CRM takes on full financial and administrative duties that include initial budget negotiation with sponsors/CROs and investigators, keeping track of the trial progress, budget and invoicing, receipt of funds from sponsors/ CROs and payments to various stakeholders involved. CRM also prepares statements of account for the principal investigators on a monthly basis to facilitate better planning of clinical trial activities.

Facilitating Initiation of Clinical Trials

Involvement of the finance team starts just prior to initiation of the clinical trial in collaboration with the legal department, principal investigators, CROs and sponsors. This is crucial, as CROs, sponsors and investigators each bring expertise required for the conduct of specific types of trials, whilst the finance team contributes with their experience working on the financial aspect of clinical trials across the board. The legal team facilitates the process by ensuring that the CTA meets local requirements. The finance team also supports CROs, sponsors and investigators when negotiating and finalising the trial budget with approval from these parties. The timeframe for this process is expedited by a dedicated team handling the details of the negotiations and preparation of the approved final budget for submission, though it is still dependent on response time from CROs, sponsors and investigators.

Financial Management During Trial Conduct

CRM’s involvement in the management of the clinical trial budget is to reduce payment time through a standardised financial process by prompt issuing of invoices and providing efficient disbursements of payments. This ensures that the financial management of clinical trials conducted by investigators at their respective clinical trial sites has a proper audit trail and is executed in an efficient and transparent manner.

Prior to the establishment of CRM, all financial transactions to and from government linked facilities were routed via established local medical societies or the clinical research arm of the Ministry of Health (Clinical Research Centre). Between 2012 and March 2015, payments to investigators had to go through a trust account under the purview of the Director of Kuala Lumpur Hospital. Due to red-tape processes, payments could take at least a month.

However, from April 2015, CRM’s role expanded to making payments out directly to investigators and study team members (specifically government-employed staff affiliated with Ministry of Health facilities) and similarly reduced the timelines to within two weeks. With the advancement of online banking facilities in Malaysia, these timelines have further reduced. In 2018, the total value of trial budget managed by CRM was RM 39.5 million, compared to 2015 which was only about RM8.3 million, translating to more than four times in the growth of the budget management.

In addition, CRM’s responsibilities encompass ensuring there are enough funds available for the smooth running of a clinical trial by keeping track of the budget and communicating with sponsors so that payments are as scheduled in the trial budget and CTA. If, for any undue reasons, receipt of funds from sponsors is delayed, CRM steps in to guarantee timely payments to vendors and study subjects, ensuring that trials are on track. All receipts and disbursements of funds are carefully tracked, and monthly statements of account are sent to the principal investigators for review. All financial processes performed by CRM are also audited by internal and external auditors, which include the National Audit Department and the Ministry of Health. During the close of a trial, CRM provides an added service of negotiating the best price for archiving trial-related documents from third-party vendors. This enables cost savings in a clinical trial budget as well as more efficient conduct during clinical trial study closure.


CRM in essence acts as an account manager with in-house expertise in clinical trial budget management. Its focus is to streamline the processes for all clinical trials conducted in Ministry of Health facilities and involving Ministry of Health staff. CRM facilitates the clinical trial process from the budget negotiation stage, receipt and disbursement of study funds and lastly, archiving services upon study closure.

Audrey Ooi (Acting Head Business of Development) and Yau Yit Huan (Head of Finance & IT) are from Clinical Research Malaysia.


1. European Medicines Agency. ICH Topic E8: General considerations for clinical trials – Step 5 (CPMP/ICH/291/95). March 1998.

2. National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia. Malaysian guideline for good clinical practice. Fourth edition. 2018.

3. Chew BH. Planning and conducting clinical research: the whole process. Cureus 2019;n(2): e4n2. DOI: 10.7759/cureus.4n2.

4. Farrell B, Kenyon S, Shalmr H. Managing clinical trials. Trials 2010;11:78. Available at http://www.trialsjournal.com/content/n/1/78. Accessed October 2019.

5. Hatfield E, Dicks E, Parfrey P. Budgeting, funding and managing clinical research projects. In: P. Parfrey and B. Barrett, editors. Methods of Molecular Biology, Clinical Epidemiology, vol. 473. Totowa, New Jersey: Humana Press, 2009; 299-3n.

6. Ooi AJA, Khalid KF. Malaysia’ clinical research ecosystem. Applied Clinical Trials 2017. Available at http://www.appliedclinicaltrialsonline.com/malaysia-s-clinical-research-ecosystem. Accessed October 2019.

Source : Journal for Clinical Studies

Establishing Clear Procedures and Improving Start-up Timeline in Malaysia’s Clinical Research Ecosystem

As delays in getting clinical trials up and running have financial implications, pharmaceutical companies and contract research organisations (CROs) are looking at ways to accelerate the study start-up process. Challenges in processes such as feasibility assessment, site selection, compilation of essential documents, submission to ethics committee, and application for investigational product import license can affect study milestones and timelines.1,2

In Malaysia, the Ministry of Health established a corporate entity, CRM, that functions as a one-stop centre to facilitate industry-sponsored research in the country to ensure an efficient start-up process. The organisation offers services such as feasibility assessment, budget negotiation, clinical trial agreement review and placement of study coordinators. This article describes CRM’s timeline in feasibility assessment, budget negotiation and clinical trial agreement review, besides the regulatory and ethics approval timeline in Malaysia.

Centralised Feasibility and Site Selection Services

The company has a centralised feasibility team that handles feasibility queries from CROs, pharmaceutical, medical device, and biotechnology companies. The feasibility team maps the sites according to disease specialities and workload, saving the time it takes to identify the right investigators and sites with interest in a particular clinical trial. It also assists interested potential investigators to address the queries and submits the completed feasibility questionnaire to the CRO or sponsor (Figure 1). Having a centralised service is far more efficient as the individual databases of the CROs and sponsors may not always be updated and sufficiently comprehensive.3 As the single point of contact, the standardised processes lead to streamlined communications which reduce delay and confusion on the ground. As a result, the turnaround time is shorter than if a sponsor or CRO were to approach individually. With CRM’s central database and feedback from the sites and investigators, a completed feasibility questionnaire can be sent back to the enquiring company within 5–10 working days (Table 1).

Prompt Review and Negotiations of Clinical Trial Contracts

The top cause of delays in clinical trial start-up time is related to contract and budget negotiations.1,4 Lack of effective communication, unclear processes, bureaucracy, and difficult to understand contracts can lengthen the time it takes to finalise the clinical trial agreements (CTAs).4,5 To address these challenges, an experienced legal and regulatory affairs department reviews and endorses CTAs (on behalf of principal investigators) for all clinical trials conducted at public hospitals in Malaysia within 14 calendar days, from the last feedback received from the party involved in the study budget negotiation (Table 1). In addition to an experienced legal team, CRM has implemented an online system for submission and internal review of CTAs to shorten the timeline for review. Prior to this, the average time to review a CTA was 59 days.

Parallel Ethics and Regulatory Approval Processes

Clinical trials that are conducted in the Ministry of Health (MOH) facilities will require ethics approval from the MREC (Medical Research and Ethics Committee), which is the sole ethics committee for Malaysia’s MOH facilities. MREC also acts as an independent ethics committee for facilities outside the MOH who do not have their own ethics committees. Malaysia’s regulatory authority for pharmaceutical trials is the National Pharmaceutical Regulatory Agency (NPRA). The NPRA is responsible for approving applications for clinical trial import licence (CTIL) and clinical trial exemption (CTX). Ethical approval is needed before the CTIL or CTX is released (Figure 1).

For medical device trials, the Medical Device Authority (MDA) oversees the issuance of the letter of no restrictions for notification of medical devices for clinical use and research supportive use. This would take 14 working days. On the other hand, notification of medical devices for clinical investigational use will go through a review by the Technical Committee of Medical Device Clinical Evaluation (TCMDCE). The issuance of a letter of no restrictions would take seven working days after evaluation by the committee. In 2019, an online system was introduced to facilitate the process.

Applications and tracking of progress are done through a local online registration of clinical studies, the National Medical Research Register (NMRR). With the NMRR being linked to the MREC, ethics approval processes are fast and convenient. An NMRR registration is also needed for CTIL/CTX application.

In Malaysia, regulatory and ethical submissions are done in parallel.6 Regulatory approval takes approximately 30 business days while MREC ethics approval takes about 50 business days7,8 (Table 1). Ethical review and approval can be as short as one month from the time of application if there are no issues/queries.8,9 On average, it takes about four months to obtain regulatory and ethics approval.10


Consistent timelines, reliability and efficient processes are important criteria for sponsors and CROs in deciding where to conduct its clinical trials. With CRM’s involvement at the feasibility and startup phase, as well as a standardised process for regulatory and ethics approval, sponsors will have better understanding and assurance on the timeline, processes and reliability of conducting clinical trials in Malaysia.

Audrey Ooi (Acting Head Business of Development) and Noorzaihan Mat Radi (Senior Feasibility Specialist) are from Clinical Research Malaysia.


  1. Clinical Researcher. Accelerating Study Start-Up: The Key to Avoiding Trial Delays (February 1, 2017). Available at https://acrpnet.org/2017/02/01/accelerating-study-start-up-the-key-to-avoiding-trialdelays/, visited on 1 November 2019.
  2. Lamberti, M.J. Clinical Trials Take A Long Time to Get Started. Here’s How to Speed It Up (March 28, 2018). Available at https://www.statnews. com/2018/03/28/clinical-trials-startup-speed/, visited on 1 November 2019.
  3. Ooi, A.J.A & Khairul, F.K. A Unique Model to Accelerate Industry-Sponsored Research in Malaysia. Journal for Clinical Studies. 11(1), 24–27(2019).
  4. Applied Clinical Trials Editors. Clinical Trial Agreement Negotiations (June 1, 2012). Available at http://www.appliedclinicaltrialsonline.com/clinical-trial-agreement-negotiations, visited on 1 November 2019.
  5. Abdul Rahman, N.A. & Yusop, N. Evolution of Clinical Trial Agreement Review in Malaysia Through Clinical Research Malaysia. (September 21,2018). Available at http://www.appliedclinicaltrialsonline.com/evolutionclinical-trial-agreement-review-malaysia-through-clinical-researchmalaysia, visited on 1 November 2019.
  6. Malaysian Investment Development Authority. Guide on Pharmaceutical Industry in Malaysia. June 2017.
  7. Ali, S., Egunsola, O., Din Babar, Z.U. & Hasan, S.S. Challenges of Conducting Clinical Trials in Asia. Int J Clin Trials. 5(4), 194–199 (2018).
  8. Society of Clinical Research Professionals Malaysia. A Guide to Conducting Clinical Trials in Malaysia (1st edition) 2016.
  9. Burton, P. Malaysia: A Clinical Trials Hub For Southeast Asia? (November 20, 2018). Available at https://pharmaboardroom.com/articles/malaysiaa-clinical-trials-hub-for-southeast-asia/, visited on 1 November 2019.
  10. Frost & Sullivan (2016) Asia: preferred destination for clinical trials. https://novotech-cro.com/sites/default/files/170217_FrostSullivan_Asia%20white%20paper_full.pdf

Source: Journal for Clinical Studies, Volume 12 Issue 1

Initiatives to Establish Capabilities in Early Phase Clinical Research in Malaysia – Applied Clinical Trials

Industry-sponsored research (ISR) has been progressively growing within Asia in the last decade. Early phase trials play a crucial role not only in drug development, but also in expanding the clinical trial ecosystem, bringing in scientific knowledge and novel medical technologies and treatments to individual countries. The benefits of conducting early phase trials also extend towards a “spill-over” effect of boosting locally conducted later phase trials leading to access of novel treatments by a large and relatively naïve patient pool and bringing in investments. With over 20 years experience in conducting late phase clinical trials, the Malaysian government realizes the positive impact of encouraging the growth of early phase clinical trials. The country also has an untapped potential that can be used toward delivering high quality early phase clinical trials such as a naïve and diverse patient pool, established and experienced infrastructure, capabilities and resources, and competitive regulatory timelines compared to its neighbouring countries. In view of this, there is a strong focus on growing the clinical trial ecosystem in the country by optimising the already existing resources while expanding and improving them to further facilitate early phase ISRs in the country. Clinical Research Malaysia (CRM) established for this purpose in 2012 and a Phase 1 Realization Project (P1RP) was launched in 2016. Supported by five pillars ranging from development of guidelines to people and capability development, the goal is to develop Malaysia to cater to early phase studies. This review describes the opportunities for growth of early phase studies in Malaysia and the initiatives taken to build a comprehensive clinical trial ecosystem to attract these trials into the country.


The conduct of industry-sponsored research (ISR) in Asia has been gaining momentum for more than a decade1-9. Frost & Sullivan’s 2017 white paper2 states that the contract research organisation (CRO) market in Asia-Pacific (APAC) is the fastest growing in the world with an expected compound annual growth rate (CAGR) of 20% (from 2016-2021) compared to an increase of 11.4% CAGR globally. This follows from estimates of clinical trial volumes increasing from 5.9% of the total global volume between 2005-2007 to 9.7% in 2011 in the APAC regionshowing a steady influx of clinical studies, as it gains a reputation for being a preferred destination for ISRs.

However, a lack of early phase trials (phase 0 and phase I trials) is evident5,6. Louisa et al.5 studied the number of ISR phase I trials between 2007–2009 found that only 6.8% of phase I trials made their way to this region. The early phase clinical trial market in 2013 was valued at approximately USD 11.9 billion with an expected CAGR of 1.5–2%reaching 4% this year3. Owing to the important roles of early phase trials that range from its scientific benefits4 to capacity building and economic advantages, most Asian countries, including Malaysia have focused initiatives into building adequate infrastructure to attract them.

Early phase trials: Asian benefits

To date (as of 12 July 2018), there are 16,248 interventional ISRs covering all phases globally, 27.2% (4,424) are early phase (phase 0 and phase I) trials10. Figures 1 and 2 show the proportion of early phase trials in Asia and Southeast Asia which are significantly smaller compared to North America and Europe.

Figure 1: Proportion of early phase ISRs in Asia, Southeast Asia, North America and Europe for the year 2018. Search criteria for these and all other values were recruiting, not yet recruiting, active–not recruiting, enrolling by invitation, interventional studies, phase 0, phase I and industry funded. Asia: North Asia, South Asia, East Asia and Southeast Asia; total number of trials in the region will defer from number of trials in an individual country due to inclusion of multicentre trials.

Figure 2: Number of early phase ISRs in Southeast Asia. Total number of ISRs registered in Clinicaltrial.gov as of July 2018 in Asia is 5,126 (of 16,248) and total number of early phase ISRs is 943 (of 4,424). Search criteria for these and all other values were recruiting, not yet recruiting, active –not recruiting, enrolling by invitation, interventional studies, phase 0, phase I and industry funded. Asia: North Asia, South Asia, East Asia and Southeast Asia; total number of trials in the region will defer from number of trials in an individual country due to inclusion of multicentre trials.

There are several benefits in conducting early phase trials in Asia. These are for example, certain diseases which are more prevalent compared to the west wherein epidemiology, health services, social determinants, co-morbidities and genetic components of the population can have an effect on how a treatment may be used, and, differences in genetics and gastrointestinal microbiome effect on the pharmacokinetics and pharmacodynamics of drug molecules4,5. There have also been concerns that racial and ethnic minorities, women and the elderly are often underrepresented in early drug development programmes making Asia an attractive destination for clinical trials1.

Therefore, the conduct of more early phase trials in regions within Asia, like Southeast Asia, plays a pivotal role to ensure that the populations proportional to the potential uses of the product after its registration and approval are conducted from the earliest stages5.

Early phase trials: opportunities for growth in Malaysia
Diverse and accessible subject pool

Malaysia, located in Southeast Asia, is a multi-racial country consisting of Malays, Chinese, Indians and numerous indigenous people who are mostly treatment naïve. This provides the genetic diversity that is important in every clinical trial. The epidemiology of diseases in an individual country is also a crucial consideration when determining the success of a clinical trial as it signifies the availability of study subjects and mitigates the risks of poor accrual rates that can cause trials to fail at huge costs11. Though a strong presence of the disease provides for a rich source of ready patients for later phase clinical trials, it also serves as an important incentive for governments to encourage testing of novel treatments in FIH trials within the country.

Patient pool with cardiovascular risks — diabetes, hypertension and hypercholesterolemia

At a global level, the top 20 indications of industry-sponsored clinical trials, regardless of phase of study include cardiovascular disease, diabetes mellitus, hypertension and hypercholesterolemia7. Conducting early phase trials targeting these conditions would be doubly beneficial to countries like Malaysia that face major public health concerns with them. Early phase trials would allow access to novel treatments and changing standards of care and with a ready pool of relatively naïve patients, sponsors and CROs would have an easy access to subjects for later phase trials. Being part of the drug development process from its early stages allows investigators and clinical trial staff to become familiar with the treatment, thereby allowing continued progress of clinical study phases to occur more smoothly.

In Malaysia, the National Health and Morbidity Survey published in 2015 showed that prevalence of diabetes mellitus among Malaysian adults of 18 years and above was 17.5% (8.3% known and 9.2% undiagnosed)12. The overall prevalence for hypertension and hypercholesterolemia were 30.3% (13.1% known and 17.2% undiagnosed) and 47.7% (9.1% known and 38.6% undiagnosed), respectively. In 2016, disease of the circulatory system was in the top five principal causes of hospital admissions (both private and public hospitals), at 7.44% of total admissions and within the top five principal causes of mortality13. With regards to Type 2 diabetes mellitus, it has more than doubled since 1996 and coupled with a prevalence of 27–31% in overweight and obesity in school children, this disease poses a major public health concern14.

With the high prevalence of cardiovascular risk factors such as diabetes, hypertension and hypercholesterolemia, not only has Malaysia a ready, diverse and relatively naïve patient pool for later phase ISRs that fit into the top 20 clinical trial indications, but it also gives the Malaysian government a strong incentive to encourage early phase trials.

Oncology patient pool

Studies in the field of oncology treatment are currently the top indication for clinical trials. Using the following search criteria, start date 01/01/2013-31/12/2017, recruiting, not yet recruiting, active – not recruiting, enrolling by invitation, early phase I and phases I-III, indication for cancer takes up 54.5% of the total industry sponsored interventional studies [10]. Additionally, projected distributions of available new active substances in the global market by disease type from 1996–2020 show15 a projected growth in oncology biopharmaceutical and pharmaceutical products making up 13% of the total new active substances.Thirty-three percent of novel drug approvals in 2015 by the United States Food and Drug Administration (USFDA) were for oncology related products whilst 27% were approved in 201716-18. In the US alone, there were 836 drugs and vaccines for cancer in various stages of clinical development or awaiting USFDA approvals19.

In Malaysia, cancer is within the top five causes of mortality and in 2016, the total hospital admissions for neoplasms were 4.2% (based on total admissions of > 3 million)13. Breast cancer is the most common of all cancers (17.7%) followed by colorectal (13.2%) and cancer of the trachea, bronchus and lung (10.2%)20.

FIH trials of oncology drugs differ from early phase trials in other therapeutic areas as they are evaluated in patients rather than healthy volunteers. The characteristics of oncology products, mainly its safety profile, do not allow for testing in healthy volunteers. In the absence of alternative effective treatments in oncology, participation in these trials using novel compounds are considered an opportunity to these patients21.

Therefore, with the global pipeline of oncology drugs in clinical development having seen a robust growth over the past two decades22, combined with the strong presence of cancer among Malaysians, not only are sponsors presented an opportunity to tap into the available pool of cancer patients, it is also a considerable push for the Malaysian government to spur the growth of early phase oncology clinical trials within the country.

Cost effectiveness

The cost of developing a new molecular entity can be over USD 1 billion with an average estimate of USD 2.6 billion8. Added to that, the development of a new medicine from identification through approval for marketing can take up to or more than 12 years. In view of the extreme financial investments, Asian countries like Malaysia, which provide treatments and medical procedures at a lower cost than in developed countries1,9, can be seen by sponsors and CROs as an ideal site for conducting clinical trials with lower investments.

The 2017 Frost & Sullivan white paper’s1 costing estimates of conducting clinical research per patient, per visit in all therapeutic areas in all phases shows Malaysia as having the second lowest cost coming before India (USD 350 vs. USD 330) while costs in Singapore was similar to that in the USA (USD 1,210 vs.USD 1,380) and that in South Korea was USD 890.

Regulatory timelines

One of the complexities of performing clinical trials in Asia is the heterogeneous nature of the regulatory processes and timelines among the countries in the region1-3,6.

However, countries in the region have attempted to harmonise these to ensure better data acceptability and reduce trial and drug approval timelines1. Malaysia is part of the ASEAN Free Trade Area (AFTA) that undertook the ASEAN Common Technical Documents (ACTD) and ASEAN Common Technical Requirements (ACTR) initiatives to standardise drug approval processes.

In Malaysia, ethics review and regulatory approvals together with import licensing and contract negotiations occur concurrently allowing for faster processing timelines and is comparable with timelines in South Korea and Singapore (approximately 2-3 months1). In a recent report, regulatory timelines have been improved to within 30 working days23 while the centralized ethics committee under the Ministry of Health has shortened its timelines to 51 calendar days.

Established infrastructure, resources and capabilities

An established and functioning network of clinical trial centres with advanced equipment and technology; knowledgeable physicians and available key opinion leaders in different specialties also play an important role in attracting ISRs1.

Malaysia has a well-developed and equipped healthcare system manned by medical doctors that practice and comply with international clinical practice standards24. ISRs in Malaysia are conducted at government hospitals, teaching institutions, private hospitals and government health clinics. Government hospitals receive and treat the largest number of patients thus presenting a unique opportunity for access to the primary care patient pool.

Developing an ecosystem for early phase clinical research in Malaysia

The Government of Malaysia realizing the potential positive impact of early phase trials for patients, scientific advancements and economic growth is stepping up its existing clinical trial capabilities by building new initiatives to drive early phase clinical research capacity in-country and develop an attractive early phase clinical trial ecosystem.

In lieu of this, the Malaysian government included the creation of a supportive ecosystem with the establishment of Clinical Research Malaysia (CRM) a non-profit company, wholly owned by the Ministry of Health24, to equip the ecosystem of clinical research in the country25. Its goal is to reach at least 1,000 clinical trials by the year 2020. Part of the initiatives stated in this section is to set up more clinical research centres, develop more Good Clinical Practice (GCP) certified investigators and improve existing IRB and EC timelines. The Phase 1 Realization Project (P1RP) initiated by CRM in 2016 was aimed at realizing this aspiration of making sure Malaysia is capable in conducting early phase studies.

The benefits of conducting early phase trials in Malaysia as laid out by the P1RP are the increase of phase II and III trials as a result of a spillover effect from conducting more phase I trials, contribution to the transfer of knowledge and technologies to Malaysians, creation of new jobs in clinical research, spurring local innovation, prevention of investment outflow and moving the country as a whole higher up the clinical research value chain. For patients, it increases the opportunity to receive novel medications or treatment that is not yet available in the market as the majority of ISRs are interventional in nature providing treatment at no cost to patients. It also provides a means for the government to expand its healthcare resources to include more patients and medications especially oncology treatment that are costly.

The P1RP Blueprint

The P1RP stands on 5 pillars, which are the establishment of guidelines for conducting phase I clinical trials in the country, people development, capability development, preparation of sites and risk management. To date, all of the P1RP pillars have been implemented and fulfilled. In the first quarter of 2019, the country’s regulatory authority has indicated that it is ready to review FIH studies by June 2019.

The P1RP strategy is multi-pronged wherein regulatory agencies are equipped with the right knowledge to review phase I clinical trials and conforming to international standards, local experts are trained with the necessary skills to analyze early phase trials through engagement with international consultants, preparation of clinical trial unit at hospitals to conduct phase I studies, and the development of an action plan to manage and mitigate any given crisis that may occur during the clinical trial process.

Development of phase I clinical trial guidelines

The Malaysian Phase I Clinical Trial Guidelines26 was launched in November 2017. Prior to this, the country did not have a specific guideline on phase I clinical trials. The effort saw the coming together of experts and investigators in the field of clinical trials from the Ministry of Health, Ministry of Higher Education, ethics and regulatory bodies as well as industry experts. International key opinion leaders on clinical trials were also invited as subject matter experts. The guidelines were based on The Association of the British Pharmaceutical Industry (ABPI) 2012 version of phase I clinical trial guidelines27 as this document took into account and expanded its content to reflect the latest changes in conducting FIH trials. The Malaysian guidelines in turn considered local regulatory bodies and agencies’ existing procedures, and the local clinical trial environment, adapting relevant areas to facilitate the applicability of the ABPI guidelines in Malaysia.

People Development

To gain knowledge and experience in phase I clinical trials so as to implement and impart these to relevant agency officers, three regulatory officers were sent to pursue their postgraduate studies at The Christie, Manchester, as well as King’s College London, under a collaborative scholarship between CRM and the Public Service Department. This will allow them to work within a leading phase I clinical trial unit and gain experience and understanding in the designing and delivering of phase I studies. This attachment is important as these regulatory officers will be the ones responsible in reviewing the dossiers of phase I studies in Malaysia.

The Ministry of Health has also planned to send local investigators to be attached at reputable phase I centres, including the Princess Margaret Cancer Center, to be exposed to the experience in conducting FIH studies.

The government has also started initiatives to bring back Malaysians from overseas. Experts or specialists from higher-income countries coming back would have an edge due to a global mindset. Coupled with an in-depth knowledge of the country, people and the culture, it creates a world-class pool of specialists that can support early phase trials2.

Initiatives to develop and perform centralized professional training for study coordinators to complement the work of investigators have also began. To attract more specialists to participate in clinical trials, the Ministry of Health now allows for 20% of a work-week (or one full day off) for investigators to focus solely on research.

Capability development

In a 2011 report presentation of the Health Committee at the 49th Parliament sitting in New Zealand28, some of the recommendations put forward to increase New Zealand’s presence in the clinical trial industry were, to establish a strong intra-governmental collaboration between different ministries, ensure a culture that values research within the public health system and requiring the Standing Committee on Therapeutic Trials to carry out all scientific reviews within 30 calendar days.

As part of the capability development pillar of P1RP, a Scientific Review Panel (SRP) for FIH clinical trials was established to support the Medical Research and Ethics Committee (MREC), a centralized ethics committee, in performing scientific evaluations of FIH trials undertaken by and/or conducted in clinical trial sites in Malaysia. The scope of review includes all FIH studies on new chemical, biological and biosimilar drugs not registered in Malaysia.

The intensity of early phase clinical trials is more time-consuming requiring more physical exams, vital signs monitoring, electrocardiogram (ECG) monitoring and pharmacokinetic laboratory tests compared to later phase trials29. The P1RP project and initiatives will harness the available resources and capabilities available within the country’s health system as well as increase its knowledge with international collaborations to ensure that the country is ready to meet with the demands of early phase trials.

Preparation of sites

Sarawak General Hospital located in a major city in East Malaysia is targeted to be fully equipped to handle early phase clinical trials. It also serves as a template for future units to be developed in other hospitals. This hospital is already a major medical centre with a ready access to large patient populations and the clinical trial centre is well-equipped and operated by well-trained scientific and medical staff.

Risk management

In June 2007, the “Guideline on Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products” was finalised by the EMA30. The scope of the guidance encompasses both biologics and new chemical entities and, was recently updated in 2016 (EMA/CHMP/SWP/28367/07)31and places the focus on the pharmacological characteristics of a new drug.

The document was created to support the transition from non-clinical to the early phase of clinical development and identifies influencing risk factors of a product, includes consideration of quality aspects, testing strategies, designs for FIH studies and mitigation strategies such as initial dosing calculation and dose escalation30.

Therefore, part of the P1RP initiative is the preparation and training of risk management guidelines and to manage any crisis in relation to early phase clinical trials. These include creation of a standard operation procedure (SOP) to prepare for and manage all types of crises requiring immediate attention during early phase trials (i.e. unexpected side effects from a clinical trial). The SOP is designed to also ensure that all actions are coordinated, timely, accurate, consistent and effective in minimising the potential for confusion, rumor and misinformation. The overall objective of this effort is to offer support to the organisation and processes of early phase trials in difficult situations and to the greatest possible extent, limit potential injury to patients, consumers or the reputation of the institutions.


CRM initiated the ACCELERATE project to move the nation’s focus further upstream to early phase drug discovery and development, utilising readily available resources in the country. The project involves converging expertise and collaborations across agencies, clinical research industries and universities on pre-clinical projects. Through this initiative, CRM has intensified collaborations with various universities and research institutes in ‘bench to bedside’ projects. The conversion of pre-clinical studies into early and late phase trials may spur discovery, local innovation and eventually manufacturing of innovator drugs in Malaysia. Additionally, it can prevent outflow of investments and move the country higher up the clinical research value chain.


Malaysia’s effort through the P1RP and ACCELRATE project underlines the government’s commitment to bring the country into a new phase in the clinical trial industry. In the local context, early phase clinical trials play a key role in enhancing the capability of the country in the development of medical science and treatment of disease as well as placing Malaysia at the cutting edge of research. To this end, the Malaysian government’s goal is to develop the country into becoming the preferred destination for industry-sponsored research.

AJA Ooi is the Business Development Manager; KF Khalid is the Former Head of Business Development, both for Clinical Research Malaysia.


  1. Frost & Sullivan (2016) Asia: preferred destination for clinical trials. https://novotech-cro.com/sites/default/files/170217_FrostSullivan_Asia%20white%20paper_full.pdf
  2. Frost & Sullivan (2017) The changing face of global clinical trials: Asia-Pacific as an ideal destination for specialty biopharma. https://www.cmicgroup.com/files/user/en/solution/pdf/Whitepaper_201710.pdf
  3. Ilancheran M, Pritchard JF (2015) Is South Korea the next emerging early phase destination? Appl Clin Trials Jan 29. http://www.appliedclinicaltrialsonline.com/south-korea-next-emerging-early-phase-destination
  4. Kapiriri L, Lavery J, Singer P, Mshinda H, Babiuk L, et al (2011) The case of conducting first-in-human (phase 0 and phase I) clinical trials in low and middle income countries. BMC Public Health 11:811. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339411/
  5. Louisa M, Takeuchi M, Setiabudy R, Nafrialdi, Takeuchi M (2012) Current status of phase I clinical trials in Asia: an academic perspectives. Acta Med Indones 44(1):71-7.https://www.ncbi.nlm.nih.gov/pubmed/?term=Current+status+of+phase+I+clinical+trials+in+Asia%3A+an+academic+perspectives.
  6. Rahman S, Majumder M (2012) Managing clinical trials in Asia: issues, threats, opportunities and approaches. South East Asia j public health (online) 2(2):80-4. https://www.banglajol.info/index.php/SEAJPH/article/viewFile/15961/11333
  7. Yathindranath S, Kureishi A, Singh S, Yeow S, Geng G, et al (2014) Evolution of the clinical trial landscape in Asia Pacific. Open access j clin trials 6:75-84. https://www.dovepress.com/evolution-of-the-clinical-trial-landscape-in-asia-pacific-peer-reviewed-fulltext-article-OAJCT
  8. Mohs R, Greig N (2017) Drug discovery and development: role of basic biological research. Alzheimers Dement (N Y) 3:651-7. https://www.ncbi.nlm.nih.gov/pubmed/29255791
  9. Murthy S, Mandl K, Bourgeois F (2015) Industry-sponsored clinical research outside high-income countries: an empirical analysis of registered clinical trials from 2006-2013. Health Res Policy Syst 13(28).https://health-policy-systems.biomedcentral.com/articles/10.1186/s12961-015-0019-6
  10. Clinical trial.gov. https://clinicaltrials.gov/ct2/results/browse?brwse=locn_cat_SE
  11. Baer A, Bridges K, O’Dwyer M, Ostroff J, Yasko J (2010) Clinical research site infrastructure and efficiency. J Oncol Pract. 6(5):249-52. https://www.ncbi.nlm.nih.gov/pubmed/21197190
  12. Ministry of Health Malaysia (2015) National Health & Morbidity Survey: Non-communicable disease, risk factors and other health problems.
  13. Ministry of Health Malaysia (2017) Health facts. http://www.moh.gov.my/images/gallery/publications/HEALTH%20FACTS%202017.pdf
  14. Tee E, Yap R (2017) Type 2 diabetes mellitus in Malaysia: current trends and risk factors. Eur J Clin Nutr 71(7):844-9. https://www.ncbi.nlm.nih.gov/pubmed/28513624
  15. Statista.com. Projected distribution of global available new active substances by disease type between 1996 and 2020. https://www.statista.com/statistics/491102/new-active-substance-distribution-projection-by-disease/
  16. U.S. Food and Drug Administration. Novel drug approvals for 2015. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm430302.htm
  17. U.S. Food and Drug Administration. Novel drug approvals for 2017. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm
  18. Buffery D (2016) Innovation tops current trends in the 2016 oncology drug piepline. Am Health Drug Benefits 9(4):233-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004820/
  19. National Cancer Institute, Ministry of Health Malaysia (2016) Malaysian national cancer registry report 2007-2011.https://www.crc.gov.my/wp-content/uploads/documents/report/MNCRRrepor2007-2011.pdf
  20. Salzberg M (2012) First-in-human phase I studies in oncology: the new challenge for investigative sites. Rambam Maimonides Med J 3(2):e0007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678815/
  21. Pharmaceutical Research and Manufacturers of America. Medicines in development 2015 report: medicine in development for cancer.     http://phrma-docs.phrma.org/sites/default/files/pdf/oncology-report-2015.pdf
  22. IQVIA (2017) Lifetime trends in biopharmaceutical innovation: recent evidence and implications.          https://www.iqvia.com/institute/reports/lifetime-trends-in-biopharmaceutical-innovation-recent-evidence-and-implications
  23. Pharmaphorum.com. Regulatory timelines in the Asia-Pacific. http://pharmaphorum.com/views-and-analysis/regulatory-timelines-asia-pacific/
  24. Ooi AJA, Khalid KF (2017) Malaysia’s clinical research ecosystem. Appl Clin Trials. Jan 26.                               http://www.appliedclinicaltrialsonline.com/malaysia-s-clinical-research-ecosystem
  25. National Key Economic Areas (2016) Healthcare NKEA fact sheet. http://etp.pemandu.gov.my/upload/NKEA_Factsheet_Healthcare.pdf
  26. Clinical Research Malaysia (2017) Malaysian phase I clinical trial guidelines. http://www.clinicalresearch.my/wp-content/uploads/2017/10/Malaysian-Phase-I-Clinical-Trial-Guidelines.pdf
  27. Association of British Pharmaceutical Industry (2012) Guidelines for phase 1 clinical trials. https://www.abpi.org.uk/media/1627/guidelines_phase1_clinical_trials.pdf
  28. Health Committee (2011) Inquiry into improving New Zealand’s environment to support innovation through clinical trials. https://www.parliament.nz/en/pb/sc/reports/document/49DBSCH_SCR5154_1/inquiry-into-improving-new-zealands-environment-to-support
  29. Craft B, Kurzrock R, Lei X, Herbst R, Lippman S, et al (2009) The changing face of phase I cancer clinical trials: new challenges in study requirements. Cancer 115(8):1592-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668727/
  30. Milton M, Horvath C (2009) The EMEA guideline on first-in-human clinical trials and its impact on pharmaceutical development. Toxicol Pathol 37:363-71.                                               https://www.ncbi.nlm.nih.gov/pubmed/19246571
  31. European Medicines Agency (2016) Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2017/07/WC500232186.pdf

Source : Applied Clinical Trials Online

Evolution of Clinical Trial Agreement

To regulate the conduct, relationships, responsibilities, and obligations of the parties involved in the clinical trial, the Clinical Trial Agreement (CTA) must be in place. The parties in a CTA are not usually limited to sponsors or contract research organizations (CROs), but also include institutions and principal investigators. The Malaysian Guideline for Good Clinical Practice, has defined the CTA as“A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.”(1)

The above definition widens the scope of CTAs, where apart from obligation of parties, the clinical trial budget must also be enumerated clearly in the Agreement.

Halsbury Laws of England has also defined the meaning of agreement in general: “A contract or an agreement is usually reached by the process of offer and acceptance and the law requires an offer on ascertainable terms which receives an unqualified acceptance from the person to whom it is made”(2)

In Malaysia, clinical trials are developing rapidly, which has allowed Malaysia to become a preferred site for clinical trials sponsored by multinational sponsors or CROs.(3) With that, Clinical Research Malaysia (CRM) is established as a one stop shop to assist the principal investigators and the industry in matters related to clinical trials. The CRM Legal and Regulatory Affairs’ role is important in providing CTA Review. The experienced CRM Legal and Regulatory Affairs department is equipped with detailed and current legal knowledge that results in a thorough and prudent review of the CTA by respecting all the applicable laws and regulations.

It is most important for the CTA to be drafted in a language that is understandable to all parties. It needs to be written clearly, limiting and defining any legal terms used. Sponsors and CROs share the same interests in relation to clinical trials, which are:

  1. collecting accurate data to support their application for marketing approval of their investigational product
  2. protecting confidential information and intellectual property
  3. complying with the applicable laws and regulations

On the other hand, from clinical trial site perspectives, their interest lies among compliance with the protocol and regulations, which includes:

  1. to be fairly compensated for their work
  2. indemnity (subject illness, injury, or death due to participation in the study or as a result of the investigational product) and sufficient insurance coverage protection to the site, principal investigator, and principal investigator’s team
  3. the ability to publish study results
  4. payment for subject in relation to the study(4)

When working towards a contract agreement between sponsors/CROs and clinical trial sites, there needs to be two-way communication and negotiation. Without having a clear and straight forward language, it is difficult to finalize the CTA in a short time. Therefore, it is essential to prepare when negotiating a contract with sponsors and CROs for items and changes that are requested. Apart from that, with the presence of experienced, proactive, and efficient CRM Legal and Regulatory Affairs Departments in reviewing CTA, the review and negotiations of CTA are done in a short period of time.

In ensuring a short timeline of CTA Review, a fixed 14-day calendar timeframe is introduced so that the site initiation visit can follow through as planned under the protocol. All CRM’s legal personnel shall maintain a timeline tracker to make sure the 14-day calendar timeframe is achieved for any one CTA review. However, it is still subject to the budget negotiation between all parties, as the clinical trial budget is incorporated as part of the CTA.


The total number of CTAs that have been reviewed by CRM between 2012 and 2017 was compiled and will be illustrated in Schedule 1. This is based on the retrospective data collection by CRM.

 Year  CTA reviewed by CRM
 2012  54
 2013  83
 2014  83
 2015  86
 2016  68
 2017  83

Schedule 1

From 2012 to 2017, a total of 457 CTAs have been reviewed by CRM.

The number of CTA review days is crucial to start a clinical trial at the site because it will affect the activities of the trial. The study cannot commence without execution of the CTA. The data on review days from 2012 to 2017 are illustrated in Schedule 2 below.

 Year  CTA reviewed timeline by CRM (average time by days)
 2012  58
 2013  42
 2014  42
 2015  92
 2016  29
 2017  13

Schedule 2

From 2012 to 2015, CRM took a longer time to review the CTAs—it took 59 days on average to review the CTA until endorsement. The CTA review days decrease from 2016 and were reported as 13 days in 2017.

The substantial improvement is mainly because:

  1. All CRM Legal and Regulatory Affairs personnel have their own Key Performance Index to review the CTAs within 14 days.
  2. In 2015, CRM Legal and Regulatory Affairs Department developed an online CTA Review System expediting the CTA review days from 59 to 13. The online review system was launched in March 2016. The online system is our own purchased internal system, where all the CTAs for Malaysian Ministry of Health sites, specifically for industry sponsored research, will be submitted in the system by the clinical research assistant from sponsors and CROs for CRM Legal and Regulatory Affairs Department’s review.
  3. The CRM Legal and Regulatory Affairs Department had also organized the CTA online review system workshop for sponsors and CROs on how the system works and their role as the external end user of the system. The system was fully utilized in 2017 and has shortened the timeline for CTA review.
  4. CRM expanded the Legal and Regulatory Affairs Department manpower from 1 in 2012 to 3 in 2017 which contributed to expedite CTAs review.


The four actions described above have reduced the CTA review days. Reduction time in review days improves the study start-up time from the CTA review point of view. This evolution enticed more sponsor and CROs to bring more clinical trials to Malaysia.5The unnecessary delays in finalizing the CTA should be avoided. As a result, the nation benefits with faster and more clinical trials for doctors and patients to include in their treatment options.


  1. National Pharmaceutical Regulatory Agency (NPRA) Ministry of Health Malaysia.  Malaysian Guideline for Good Clinical Practice (Fourth Edition). Glossary 1.21. pg 10. 2018.
  2. Halsbury Laws of England; 4thedition, Reissue 1998, para 632. 1998.
  3. Jenny Maganram Goh, 31 October 2016, Moving medical research forward: Malaysia aims for 1,000 clinical trials by 2020 (https://today.mims.com/moving-medical-research–forward–malaysia-aims-for-1-000-clinical-trials-by-2020)
  4. Pfeiffer, J. and Windschiegl, M. (2016) Managing Clinical Trial Budgets and Contracts. LAD Publishers. Georgia.
  5. A.J.A. Ooi, K.F. Khalid, MD, January 26, 2017, Malaysia’s Clinical Research Ecosystem (http://www.appliedclinicaltrialsonline.com/malaysia-s-clinical-research-…)

Nurul Atiqah Abd RahmanNorafizaa Yusop, Clinical Research Malaysia


Malaysia’s Clinical Research Ecosystem and the role of CRM in Advancing ISR in the Country

The impact of globalization resulted in the shift of industry-sponsored clinical research (ISR) from high economic countries to Eastern European, Latin American and Asian countries. Since 2008, Asia has shown significant growth in interventional studies with an average of 8% growth. Asian countries offer two main benefits for conducting clinical trials, which are its large and diverse patient pools, and the relatively lower cost of clinical trial conduct. Malaysia has many inherent qualities that make it an ideal country for conducting clinical trials such as a multi-ethnic population, which is relatively treatment naïve, competitive costs and an established healthcare infrastructure. Additionally, Malaysia has existing experience, facilities, processes, regulations and manpower in conducting clinical trials for over 20 years. The current Malaysian Economic Transformation Program (ETP) targets clinical research as one of its main drivers in economic growth. Therefore, the government of Malaysia, with an aim to promote and increase the number of clinical trials in Malaysia established Clinical Research Malaysia (CRM) in 2012 with the objectives of effectively increasing the speed, reliability and delivery of outcomes for all stakeholders involved. This review outlines the role of CRM, its achievements, future endeavors and the opportunities it provides for sponsors to carry out clinical trials in Malaysia.

Asia’s Clinical Development Rise

Traditionally, ISR has been conducted in high-income countries in Europe and in the United States of America (USA) due to the established research infrastructure and presence of major pharmaceutical companies in these countries.1However, globalization resulted in shifting ISR outside high income countries. The major beneficiaries of this shift have been Eastern European, Latin American and Asian countries. This change in the clinical research landscape, has substantially increased the number of registered clinical trials globally, as evidenced by two separate studies done analyzing the number of clinical trial registrations based off various global clinical trial registries. Viergever and Li analyzed the number of registered clinical trials based off the International Clinical Trial Registry Platform (ICTRP), which was established by the World Health Organization (WHO) in 2006. The database was mined to include all studies registered up to 31stDecember 2013. After excluding all observational studies, a total of 186,523 clinical trials from 16 clinical trial registries were included in the analysis. The number of registered clinical trials showed a substantial increase constituting a seven-fold rise between 2004-2013.2 In another study conducted by Yathindranath et al, 15 online databases that contained registration for clinical trials globally and clinical trial registries in Asia were used. In Asia Pacific, clinical trial volumes have been steadily growing from 5.9% of the total global volume in 2005–2007 to 9.7% in 2011.3This shows that during these time periods, this region has become an important region for the clinical trial industry.

Asia specifically has shown significant growth in registered interventional clinical studies from 2008–2012 with an average growth rate of 8%,4whilst North America showed a decline of 2% during the same time frame.4Sixty percent of the world population reside in Asia.5Therefore, as potential clinical trial hubs, Asian countries offer large and genetically diverse patient pools who are mostly treatment naïve, and a lower cost in conducting clinical trials in the face of limited patient pools and rising costs in the USA and Europe. Countries in Asia also offer varying disease epidemiology5in both infectious and chronic diseases due to the rise of lifestyle diseases such as diabetes, obesity, hypertension and various cancers due to urbanization.3 Government interest in expanding clinical trial research, large hospital infrastructures and an increasing number of clinical researchers, growth in the pharmaceutical sector and an increase in investment in research and development by pharmaceutical companies also contribute to Asia being an attractive destination to conduct these studies.3,5

The Malaysian Economic Transformation Program

The government of Malaysia, with an aim to provide sustained growth in various economic sectors initiated the ETP which comprises 12 National Key Economic Areas (NKEA). Clinical research is listed under the Healthcare NKEA, the second among the Entry Point Projects (EPP2). Through this project, the government of Malaysia intends to promote clinical research in Malaysia and aims to increase the number of clinical trials from about 200 clinical trials per year to at least 1000 new and ongoing clinical trials by the year 2020.6


Malaysia comprises 13 states; 11 states in Peninsular Malaysia and two states Sabah and Sarawak, in the northern part of Borneo Island.7Peninsular Malaysia is neighbored by Singapore in the south and Thailand to the north.

The Ministry of Tourism tagline for Malaysia, “Malaysia truly Asia” depicts the diversity of races in this culturally rich land. The population estimates for 2016 stand at 31.7 million (107 males per 100 females) people out of which 89.7% are Malaysian citizens. Three major races and a minority of other races make up the Malaysian population (68.7% Bumiputera; consisting mainly of the Malay race, 23.4% Chinese, 7.0% Indians and 1% other races).8 The median age is 28 years and the largest age group, between 15-64 years, make up 69.4% of the population. The proportion of the elderly is also increasing due to better access to healthcare. Malaysia has a growing urban population. In 2016, the urban population is estimated at 75% of the total population (compared to 57% in the East Asia and Pacific region).9

Malaysian healthcare system

The healthcare system in Malaysia is two-pronged with a major contribution from the public health sector. Both public and private healthcare systems are closely monitored by the government under the Ministry of Health, and share a similar system that offers primary health and specialist care. The public health system is far reaching with presence in the rural and urban settings, while private healthcare is mainly found in the urban areas.

Malaysia’s public health system is based on the World Health Organization’s (WHO) district health system model.10The larger district health clinics are managed by family medicine specialists and are self-contained with their own basic laboratories, and X-ray and ultrasound facilities. These district health clinics are capable of attending to both acute surgical and medical cases as well as following up patients with stable chronic diseases, in addition to providing maternal and child healthcare services. The smaller community clinics that are under the purview of these district health clinics are most often run exclusively by registered nurses and mid-wives who are trained to provide preventive maternal and child services including home visits.10

Primary care in the private healthcare system is provided by privately owned general practice (GP) clinics, stand-alone specialist clinics and outpatient specialist clinics in private hospitals. In 2008, there were an estimated 6,000–7,000 GP clinics and for every 10 primary care visits, 6 were to GP clinics. Some GP clinics, especially those who belong to a group practice have added facilities such as portable blood analyzers, and x-ray and ultrasound services.11GP clinics like the district health and community clinics are located in both urban and rural areas of the country.

In 2013, 40.2% of all hospitals in Malaysia (N=351) were categorized as public hospitals (this included Ministry of Health hospitals, university hospitals and Ministry of Defense hospitals) whilst 59.8% were private hospitals.12About 47.5% and 67.1% of the public and private hospitals respectively provide specialist services. Data from 2011 show an increasing trend in specialist care for example from 2010 to 2011 there were 3 additional hospitals providing oncology services (total of 58 hospitals in 2011) and 10 new hospitals started providing psychiatric care during the same time frame (total of 94 hospitals in 2011).

Malaysia’s clinical research ecosystem

In recent years, Malaysia has been striving hard to utilize the opportunity created due to the shifting of clinical trial bases of the pharmaceutical industry to Asia.

Malaysia has inherent benefits to conduct clinical trials such as its large multi-ethnic population that offers genetic diversity, established and good public and private healthcare systems, a consistently increasing number of Good Clinical Practice (GCP) trained and compliant investigators and support staff, an established and comprehensive ethical review process by ethics committees, adherence to intellectual property rights (IPRs) and competitive trial costs compared to other Asian countries. Malaysia also boasts shorter regulatory and ethics approval timelines for ISR that are comparable with countries like Hong Kong, Japan, Singapore, Taiwan and South Korea (Table 1).13

Generally, clinical research is conducted in Malaysia at university hospitals, Ministry of Health hospitals and increasingly at private medical centers across the country. The wide network of local Ministry of Health, health clinics represents a unique opportunity for access to a previously untapped, primary care patient pool.

The National Pharmaceutical Regulatory Agency (NPRA) ensures the quality, efficacy and safety of pharmaceuticals in Malaysia through the registration and licensing scheme. The NPRA acts as a Secretariat to the Drug Control Authority (DCA).14The DCA is empowered to review matters related to product registration, and approve or reject application for Clinical Trial Import License (CTIL) or Clinical Trial Exemption (CTX) among others. The IRB structure in Malaysia depends on the location or type of facility conducting the research. Generally, most university hospitals have their own local IRB/IEC, while research conducted at Ministry of Health hospitals fall under the purview of the central IRB, which is the Medical Research and Ethics Committee (MREC).14

CTIL/CTX applications are submitted to the NPRA following the Guidelines for Clinical Trial Import License (CTIL)/Clinical Trial Exemption (CTX). The NPRA screens the application dossier for completeness before handing them over to the DCA for a decision to be made. Once approval is granted by both the DCA and MREC (or other accepted IRB/IEC), the NPRA issues the CTIL/CTX and regulatory approval letters to begin the clinical trial (Figure 1).15Generally, a CTIL/CTX application is processed within 30 working days while the MREC approval takes 50 working days, if no amendments to the submitted documents are required. Both CTIL/CTX and MREC applications can be submitted in parallel. Users (PI/CRO/Sponsor) who intend to submit to MREC (or other accepted IRB/IEC) are required to register with the National Medical Research Register (NMRR) website and obtain a user account that can be used for all submissions thereafter.

Clinical Research Malaysia

CRM is a non-profit company wholly owned by the Ministry of Health. CRM was established in June 2012 to position Malaysia as a preferred global destination for ISR and to function as an enabler and facilitator to the industry and medical fraternity for the conduct of clinical trials.

CRM plays an important role to improve the local ecosystem to support growth in ISR, facilitate the needs and requirements of industry players, grow the pool of capable investigators, support staff and trial sites, and improve their capabilities and capacities to conduct ISR. With the Ministry of Health’s support and clear knowledge of the local research environment, CRM is able to provide sponsors and contract research organizations (CROs) with an extensive range of services that include complementary feasibility studies, investigator selection, placement and development of study coordinators, management of trial budget and review of clinical trial agreements.

Prior to CRM’s inception, there were several challenges faced in the effort towards expanding the clinical research environment in the country. These hampered the operations of ISR in Malaysia in terms of speed, reliability and delivery of favorable outcomes to the relevant stakeholders. The challenges were the time consuming hiring process that involved government bureaucracy and acquisition of assets, poor transparency of fund management, and lack of activities to increase the number of investigators and well-equipped trial sites for the conduct of clinical trials. There was also a need for a locally placed “one-stop” center to facilitate sponsors/CROs interested in conducting clinical research in Malaysia by championing collaborations with the regulatory agencies, customs officials and investment authorities. Furthermore, though the interest in clinical research among the existing investigators and support staff were high, there was no clear clinical research pathway to encourage and develop their potential in this area.

As part of Malaysia’s ETP, CRM was established with the objectives of facilitating the conduct of clinical trials in Malaysia with the aims to ensure the reliability, speed and delivery of outcomes for all stakeholders. These objectives include the improvement of clinical trial sites by addressing their needs and allocating highly trained study coordinators, increasing well-trained and GCP compliant investigators through training and awareness campaigns, implementing strategies and procedures for feasibility assessments and investigator selection, providing transparent and efficient trial budget management, initiating collaborations with local, regional and global stakeholders, attracting global pharmaceutical and CRO investments, inspiring private hospitals and universities to be part of the expansion of the clinical trial environment, and investigating and addressing the perception and awareness of clinical trials among healthcare professionals, administrators, patients and the public.

Achievements of CRM

CRM has developed five key strategies to put in place a comprehensive, enabling and supportive ecosystem that meet the needs of industry players and the medical fraternity. The five strategies are to grow the pool of investigators and sites, attract new ISR to Malaysia, collaborate with stakeholders, create awareness of CRM and develop human capital.

CRM is entrusted to compile and track the number of ISRs from MREC and all IRB/IECs and these numbers are reported annually to the Malaysian government. Between 2010 and 2015, Malaysia has seen a steady increase in the number of ISR from 143 trials to 201 trials within the five-year period (Figure 2). There was no increase in the number of trials between 2014 and 2015. During this time period, a global decline (by 10%) in the number of ISR was recorded, and Malaysia was also affected by it. The number of sponsors and CROs who utilized CRM’s services however, recorded a sharp increase in 2016 compared to 2014. Up until September 2016, there was more than a 200% growth in the number of sponsors while the number of CROs doubled during this time period, indicating the confidence of foreign investors in Malaysia’s capability in conducting ISR (Figure 3). In this same time frame, CRM’s experience as a site manager has expanded to 25 therapeutic areas.

The gross national income (GNI) created by clinical trials in 2015 totaled over USD 28.01 million, an increase of USD 17.03 million from 2011. There was a growth in the number of Principal Investigators (PIs) between January and September 2016 (Figure 4) after the country recorded a sharp decline in 2015. One of the reasons for the decline was due to senior investigators leaving their services because of retirement with many of them not having put in place proper succession planning. Additionally, there was lack of support in promoting ISR to junior doctors during that time. It was in 2015 that CRM actively took up this role to increase the number of investigators by supporting 8 State Research Days in 2015 that saw an impressive 550 abstracts submitted from all over the country. Seeing its success, CRM has committed to support 11 of these State Research Days in 2016. State Research Day is a Ministry of Health initiative which is organized nationwide annually. Its aim is to provide an avenue and opportunity to the allied health and medical personnel to share their research findings, besides providing recognition and encouragement for them to engage in research. It is also a platform to raise awareness on the importance of research in improving patient care in the country.

In its infancy in 2012, CRM had 22 study coordinators that were placed throughout Malaysia at various sites conducting ISR and this number has grown to 93 study coordinators as of September 2016. CRM being true to its national agenda has expanded its operation beyond the realm of Ministry of Health sites. It has received requests to support investigators and sites in Ministry of Higher Education hospitals and private hospitals alike. The strategies employed by CRM had in 2015 created 1118 high skilled jobs in the clinical research industry in Malaysia, more than the 1000 it was entrusted to create by 2020.

Among the various initiatives taken so far by CRM to improve the clinical research ecosystem have been to recruit, train and develop Medical Officers into future investigators, invest in various clinical research sites by equipping these sites with the necessary infrastructure to conduct clinical trials, shortened the clinical trial agreement (CTA) review and approval timeline from 14 working days to 5 working days, seconded staff to the MREC and to the Medical Device Authority (MDA) to improve approval timelines and assist in queries from the industry, and formed partnerships with the media to create awareness of clinical trials. Furthermore, CRM organizes “Industry Dialogues” twice a year to understand and address issues being faced by the pharmaceutical, biotechnology and medical device industry as well as CROs.

CRM is currently incollaboration with the Drugs for Neglected Disease initiative(DNDi), a not-for-profit research and development organization that works to deliver new treatments for neglected diseases. With this project, CRM plans to develop a public health approach to hepatitis C within the framework of the future National Strategic Plan on viral hepatitis. The immediate goal of this initiative is to conduct clinical studies of promising new treatment regimens for hepatitis C which will be followed by scale-up of treatment for patients, with the overall objective of ensuring equitable access to affordable and effective treatments for patients suffering from this disease in Malaysia. A scale-up of treatment is necessary in order to have an impact on the number of cases, which are steadily increasing. Due to this surge in the number of cases and the high prices of new hepatitis C medicines, it has been almost impossible for the Malaysian government to provide access to treatment at the necessary scale. The trials conducted with the support of DNDiare anticipated to introduce a new therapy as soon as possible and a scale-up to reach all patients in Malaysia.

Overall, the strategies initiated by CRM from its inception in 2012 have been very encouraging. It achieved 94% of its key performance index 1 (KPI 1) determined by the number of ISRs conducted in Malaysia during the year 2015 (201 ISRs conducted vs. goal of 214 despite a 10% global decline). Meanwhile, the number of clinical trials performed in Ministry of Health facilities (KPI 2; 128/120) during the same year achieved 107% of its KPI 2.

Future endeavors of CRM

The Ministry of Health through CRM is driving an initiative to prepare Malaysia to conduct Phase I clinical trials in the next 3 years. This initiative, termed the Phase I Realization Project (P1RP) was design as the Malaysian government wishes to push its involvement in all phases of drug development. The 5 pillars that support the P1RP blueprint include the development of Phase I Guidelines, People Development, Capability Development, Preparation of Sites andRisk Management.The initiative that started in May 2016 will see the completion of the Phase I clinical research ecosystem in 2019. The capture of Phase I trials may result in a spillover effect of more Phase II and III trials into Malaysia. Among the many economic advantages in opening Malaysia’s doors to early phase studies include the transfer of knowledge and technologies to Malaysians, creation of new jobs in clinical research, spur local innovation and prevent outflow of investments. Conducting early phase studies in accordance with international regulatory standards would also drive capacity building for local ethical review, facilitate healthcare infrastructure development, increase economic activity by encouraging research into more innovative products and reduce the culture of dependency on developed countries.


Established by the Malaysian Ministry of Health in 2012, CRM exists to advance global health solutions for a brighter and more hopeful future for the people by providing speedy and reliable end-to-end clinical research support for quality studies.

CRMs innate understanding of the local clinical research landscape with the international standards of operations coupled with fundamental backing of the government ministries provides them with an incomparable advantage to work with partners from the nascent stages of development to materialization of the end product, in order to deliver better treatment and high skilled job opportunities.

Moving ahead, CRM plans to expand its horizons through P1RP to spur high impact Phase I clinical trials into Malaysia that may result in a spill-over effect of more later phased trials into the country. These accomplishments are taking Malaysia closer to the goal of being a ‘globally preferred destination for clinical research’.

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.


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Yasin S, Chan CKY, Reidpath DD, Allotey P. Contextualizing chronicity: a perspective from Malaysia // Globalization and Health, 2012;8:4, doi: 10.1186/1744-8603-8-4
Aljunid S, Primary health care and health information needs in Malaysia. Presented at United Nations University-International Institute for Global Health. http://www.whofic-apn.com/pdf_files/4th_17_35p.pdf. Accessed 06.10.16
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Drug Control Authority, Ministry of Health. Terms of Reference. 2013
Society of Clinical Research Professionals Malaysia. A guide to conducting clinical trials in Malaysia. 2016

Source: Applied Clinical Trials

Ensuring Effective Financial Management in Sponsored Research in Malaysia

The principles of developing, conducting, analysing and subsequently reporting clinical research are widely known.1- 3 However, the success of a clinical trial goes beyond these principles. It also requires a structured, viable and business like management of the whole process, without which trials may fail.4 A critical part of managing clinical trials is a solid, well thought out clinical trial budget.