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.
- Ooi AJA & Khalid KF. Malaysia’s clinical research ecosystem. Appl Clin Trials. (2017). http://www.appliedclinicaltrialsonline.com/malaysia-sclinical-research-ecosystem.
- 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).
- 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).
- 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.
- 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.
- Frost & Sullivan. Asia: preferred destination for clinical trials. (2016).
- Sim A & Astudillo D. Working with Clinical Research Malaysia to move Malaysia forward. Ann. Clin. Lab. Res. 3(333), 1 (2015).
- 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).
- Government of Malaysia. General Orders Chapter D, Clause 5. (1993).
- Clinical Research Malaysia. Annual Report (2017).