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.
- 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.
- 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.
- 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).
- 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.
- 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.
- Malaysian Investment Development Authority. Guide on Pharmaceutical Industry in Malaysia. June 2017.
- 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).
- Society of Clinical Research Professionals Malaysia. A Guide to Conducting Clinical Trials in Malaysia (1st edition) 2016.
- 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.
- Frost & Sullivan (2016) Asia: preferred destination for clinical trials. https://novotech-cro.com/sites/default/files/170217_FrostSullivan_Asia%20white%20paper_full.pdf