International Clinical Trials Day is commemorated worldwide on or around May 20. It was first launched in 2005 by the European Clinical Research Infrastructure Network (ECRIN), in recognition of the day on which James Lind started, what is widely believed to be the first clinical trial, in 1747.
Aboard the HMS Salisbury of the British Royal Navy fleet, Scottish surgeon mate James Lind conducted his “fair test” in search of a treatment for Scurvy, which we now know is caused by a deficiency of Vitamin C, and which is thought to have killed more British sailors than French and Spanish arms.
Although the method of allocation is unknown, in his “controlled trial,” he recruited 12 navy subjects, assigning two each of them to six different potential daily treatments for an equal duration of 14 days. Crucially, due attention was given to controlling potential confounding factors and minimizing bias, both of which are essential in well-designed clinical trials.
A clinical trial, is thus, distinct from observational or epidemiological research. Randomized controlled trials (RCTs) are performed with the objective of investigating a clinical question wherein there is no certain answer as of yet, or in trial terminology, “clinical equipoise.”
They involve a great deal of attention to detail in terms of design, with scrutiny from ethical review boards and regulatory authorities at each phase. International Clinical Trials Day is an opportunity to celebrate the achievements of clinical researchers and research organizations, and indeed to raise awareness of clinical trials as well as the need for randomized evidence among the general public. The Covid-19 pandemic is perhaps the greatest testament to the necessity for good randomized evidence in informing clinical practice. While some high-income countries also struggle with implementing well-designed clinical trials owing to a variety of reasons, in the context of Bangladesh, there is an urgent and dire need to introduce the concept of this distinct methodology of research into the medical landscape.
A massive population
With a population of over 160 million, and a formidable burden of both tropical and non-communicable diseases (NCD’s), Bangladesh harbours a massive patient population in whom potential research questions relevant to local epidemiology need to be investigated, and answers pertinent to the resident population must be sought. However, there are many challenges that need to be overcome.
Perhaps the most detrimental barrier is a deficiency of skilled manpower, with very few researchers familiar with Good Clinical Practice (GCP) guidelines and standards in clinical trials conduct.
Apart from the chief investigators, trial processes involve many intricacies requiring trained staff at every level, eligible to participate as members of trial steering committees, data safety monitoring boards, ethical review committees, research coordinators at sites and data managers.
There are also concerns around the high demand of overhead by some local CROs, with researchers being compelled to seek the expertise of overseas CROs instead, in order to meet costs.
There has also been debate about the ethics of research in low-resource settings. Administrative delays, particularly in terms of ethical committee approval, are a prime barrier to conduct time-dependent clinical trials, and impedes opportunities to research pertinent to local populations, especially emergency situations like pandemics, where time is of essence.
Barriers to research
Conducting quality clinical trials, even with the very least resources requires funding required to cover financial costs at various stages of the trial, including the incorporation of trained personnel to run appropriate trial processes and other logistical issues.
Especially in academia, very often busy clinicians are compelled to take on the additional commitments to research, in the absence of protected research time, and lack of funding to employ even basic level ancillary staff.
This remains a significant barrier to research development locally. Despite recent economic strides, made as a nation, few organizations are invested in providing sufficient grants to finance large-scale projects with the potential to yield meaningful results.
Furthermore, overseas fund acquisition through proper channels is a time-consuming process with a high level of a legislative barrier. An additional burden is the restrictions on the international transfer of biomaterials, which can hinder the ability to conduct centralized translational research.
Thus, the issues are multi-faceted and so indeed, are the solutions. Establishing trial infrastructure, allocating more resources to research, and a transformation towards research-friendly legislative processes are needed.
Furthermore, the importance of appropriate training of research teams including ancillary trial staff, and efforts to increase population and community awareness towards trials, cannot be understated. In this respect, necessary steps must be taken to build meaningful partnerships between academia, the government, industry, CROs, and other local stake-holders.
Multi-national collaborations and linkage to the international organizations are also imperative to build capacity locally, equip physicians as well as researchers with the necessary training and infrastructure to conduct independent research. While formal training in trial research methodology is a necessity, many of the skills pertaining to trial processes and conduct are picked up on the job, through experience and mentorship, which require building and cultivating networks of collaborators for future projects.
Finally, there is a tendency locally, to believe that research and clinical work run on parallel tracks, never to meet. In reality, it should be the exact opposite, where clinicians involved in daily clinical care and those who understand the nuances of a question, are also directly involved in recruiting patients for research.
The onus should be on the local practising clinician to delve into potential research questions relevant to local epidemiology, and seek answers pertinent to the resident population.
This attitude needs to be instituted at a grassroots level, with prospective researchers being introduced to research and biostatistics at early stages of their careers, with encouragement to participate in, and conduct basic research projects.
It is expected that such a positive change in attitude, and the cultivation of a research-inclined environment will automatically spur on researchers to work towards overcoming challenges to the conduct of clinical trials in Bangladesh.
Dr Aaysha Cader, MD, MRCP is an Assistant Professor of Cardiology at Ibrahim Cardiac Hospital & Research Institute, Dhaka, and a part-time MSc Clinical Trials student at the University of Oxford. Dr Mohammad Jahid Hasan, MBBS, MPH is the Executive Director of Pi Research Consultancy Centre, Bangladesh. Views expressed here are the authors’ known. Email: [email protected]. Twitter: @aayshacader.
