Speakers highlight difference between registered RCTs ad publication, challenges & barriers to conducting trials
Iran and Malaysia have made tremendous progress in training human resource, clinical infrastructure and development of clinical trial sites
Clinical Trials Summit of Pakistan will be held regularly – Prof Saeed Hamid
KARACHI: Pakistan’s First Clinical Trials Summit jointly organized by Aga Khan Univesity and National University of Medical Sciences (NUMS) attracted a large number of researchers involved in clinical trials from many countries in the region besides representatives from WHO Easter Mediterranean Region, representatives from Drug Regulatory Authority of Pakistan, Contract Research Organizations and representatives from numerous Clinical Trial Units functioning in Pakistan. Speakers highlighted the difference between the registered Clinical Trials and Publications besides challenges in publishing clinical trials, barriers to conducting trials, development of proper clinical research infrastructure, training of human resource.
Dr. Arash Rashidian
Iran and Malaysia have made tremendous progress in training human resource, clinical Trialists and development of proper clinical trial sites which was highlighted by the speakers from these countries. Addressing the participants Dr. Arash Rashidian Director of Science Information and Disseminating at WHO EMRO called upon the researchers to conduct clinical trials on diseases which are prevalent in the Eastern Mediterranean region like tuberculosis and Cutaneous Leishmaniasis. In his plenary talk on WHO strategies for enhancing the conduct and use of research for health in the EMRO Region, he also noted that most research is not focused on national priorities and very limited progress has been made in establishing evidence to improve policy making.
Before the Covid19 pandemic, no vaccine trial was conducted in this region. After Covid we had four vaccine trials in the region of which one major trial was conducted in Pakistan. Now the number of trials being performed in the region is going up. There was no justification at all in conducting trials enrolling seventy patients or two hundred patients which does not make any sense. There are studies which should not be conducted. It is the large trials which have changed global practices, he remarked. He also referred to challenges in publication of clinical trials.
Prof. Wasim Jafari chairing one of the sessions during the recently held
First Pakistan Clinical Trials Summit at Aga Khan University.
Dr. Vasee Moorthy Senior Advisor, R&D Science Division from WHO discussed WHO Normative guidance for Best Practices in Clinical Trials. He emphasized the importance of strengthening local leadership and national support for sustained infrastructure and funding, enhancing engagement with patients, communities and public in trial life cycle, addressing barriers to clinical trials in underrepresented populations. He also referred to enabling well designed, policy relevant trials including adoption of incentive designs and digital technologies.
There are serious gaps in ethical oversight and workforce. Many countries in the EMR lack adequately trained personnel to support ethical review processes and trial implementation. Research Ethics Committees are often under-funded, understaffed and lack sufficient resources. It has impact on trial quality and timelines. These capacity gaps hinder the ability to maintain consistent ethical standards leading to delays in trial approval and inconsistencies in trial execution. Eventually this undermines the credibility and efficiency of clinical research in the region. Investing in workforce training for ethics committee members, increasing funding for ethical oversight and building capacity in trial implementation is needed.
Dr. Arash Rashidian from WHO EMRO alongwith Prof. Dr. Akbar Fatouhi,
Dr. Arshad Altaf participating in the panel discussion during the Clinical Trials Summit organized by Aga Khan University in collaboration with NUMS held
at AKU recently.
A significant gap exists between the number of registered clinical trials and their corresponding peer review publications. Trials that fail to yield statistically significant results or encounter operational challenges may not be published thus limiting the availability of comprehensive data. This lack of complete and accessible trial data hinders meta-analysis and evidence synthesis reducing the ability to draw reliable conclusions and informed policy decisions. There are opportunities for improvement by enhancing mandatory reporting of all trial results and promoting the publication of negative or inconclusive results will improve transparency and accessibility of clinical research findings.
Yet another important issue he highlighted was that some clinical trials in the EMR are conducted in isolation from routine healthcare delivery limiting patient accessibility thereby reducing the potential for real world data collection.
This disconnect between clinical research and healthcare systems reduces the impact of research findings. This lack of integration of health care systems also make it much more difficult for patients to participate in trials especially in primary care settings. He suggested embedding the clinical trials within healthcare systems to enhance patient access and integration with routine care. Continuing he advocated accelerating access to fit-for-purpose training packages for clinical trials, improving coordination and streamlining regulatory and ethics reviews, engaging clinical practitioners to integrate clinical trials into health systems and practices, reducing waste and advancing transparency. Expanding mutually beneficial mufti-national research and clinical trial collaboration will be extremely helpful.
Dr. Arshad Altaf
Speaking about the most published clinical trials in the EMR, he pointed out that most of it was from Iran. The number of published papers from various countries in the region are mentioned in Table-I: As regards implementing change and guidance for best practices for clinical trials, he suggested that we need to undertake trials which address key evidence gaps, risk based proportionate approaches, patient and community engagement, enroll representative population. Emphasis should always be on public health, clinical practice oriented trials and optimizing impact of existing interventions. Dr. Arshad Altaf from WHO EMRO Cairo shared the preliminary results of EMRO wide landscape analysis of national clinical trial ecosystems.
Iran’s Experience of RCTs
Prof. Akbar Fatouhi Prof. of Epidemiology at School of Public Health at Tehran Univesity of Medical Sciences shared the Iran’s experience of conducting RCT and its governance. The two main units are located at Tehran Univesity and Iran University of Medical Sciences where most of the RCTs are performed. He pointed out that there are too many trials being performed but there is a gap between the number of registered trials and published RCTs. In addition there are too many small trials which does not provide much information. Most of them are researcher driven, priority is not clear and there is limited interchange with the industry. In addition there is also limited international collaboration which was one of our main problems.
Commenting on the presentation Mr. Saeed Ghani remarked that there are too many hurdles in conducting clinical trials. We need to learn from Iranian experience. We need to give incentives to researchers. Once incentives are provided, it will encourage research. We also need to promote the conduction of clinical trials in Pakistan, he added.
Replying to a question about funding, Dr. Arash Rashidian from WHO remarked that WHO does not provide funding for research. It is only in exceptional cases. He further stated that regulations are always better and they are also necessary. He once again reiterated that we need to conduct studies on diseases which are prevalent in the Eastern Mediterranean Region.
DRAP’s Role in Clinical Trials in Pakistan
Dr. Abdullah Abro from Drug Regulatory Authority of Pakistan shed light on DRAP’s role in advancing clinical trials in Pakistan. Tracing the history he said that previously we had Drugs Act 1976 but in 2011 with 18th constitutional amendment, health was devolved to provinces. Then we faced some serious issues in health sector related to drugs safety. Hence DRAP Act 2012 was enacted by the Parliament. He also traced the history of Drugs Act 1940 to DRAP Act of 2012. We have a central drugs laboratory at Karachi and in addition we have NCLB at Islamabad. DRAP has thirteen divisions. He also discussed the mandate given to DRAP in detail. DRAP has published guidelines for conduct and reporting of good clinical trials. We have also developed Good Clinical Practice Guidelines. All trials are approved by National Bioethics Committee (NBC).
The Clinical Studies Committee in DRAP is headed by a Director. There is a Division of Pharmacy in DRAP. He also discussed the composition of Clinical Studies Committees. We always engage PPMA and Pharma Bureau representatives as observers as we wish to ensure transparency. He also disclosed that there are 109 Clinical Sites approved for trials all over Pakistan. So far seventy eight clinical trials have been conducted in Pakistan. We have provided online resources for the researchers. Timeline for the approval of the trial has also been reduced to two to three months, he added.
Dr. Essam Karwash from MHRA of UK was the next speaker who made a presentation on “MHRA Regulatory Perspective on First in Human Clinical Trials. He also pointed out that they assess the ability of the researches to conduct intervention trials on drugs in UK. We also review safety profile of products. There is a risk associated with all the trials. We ensure that the benefit risk ratio is favorable for trial subjects and the trial design protects the scientific integrity of data. However, MHRA does not evaluate the suitability of the trial in the context of overarching drug development. We will also not optimize protocols, advice on formulation development. In Non clinical assessment we look at the safety of the product from the perspective of non-clinical testing and the protocol design. In Pharmaceutical assessment in Phase-I we look is the product fit for purpose given the stage of development, dosing efficacy for small doses and has it been manufactured in the same way as the pre-clinical material.
In clinical assessment we look is the trial design appropriate based on available data, study population safety monitoring, starting dose and dose escalation and the criteria for stopping the trial. At this stage we also look at the safety of the trial from the perspective of protocol design, human data, and dose, duration of treatment, potential efficacy, potential hazards, and risks besides safety monitoring and reporting. MHRA can request for expert advice. The result of this detailed assessment is that trial is accepted with or without conditions, we can also request for further information which does not mean rejection of the application. In UK all FIH studies are peer reviewed by the CTU team and high risk trials receive independent external expert advise.
He also gave details of sources of advice from MHRA CTU and discussed the estimated framework on how to handle data if the trial is discontinued due to lack of tolerance. He then referred to what was important for Paksitan and other Low Middle Income Countries (LMIC) as regards publication, dissemination sharing knowledge and capacity building.
Speaking about the hot topics in clinical trials, Dr. Essam Karwash mentioned key areas and developments have a significant impact on trial design, analyses, interpretation and value. Health technology assessment, real word data and synthetic controls, patient preference and engagement besides cost.
Transforming Malaysia into preferred site for Clinical Trials
Ms. Audrey Ool Head of Business Development in Clinical Research Malaysia (CRM) discussed how they are trying to transform Malaysia into a preferred destination for clinical trials. She also discussed in detail their journey from 2012 to 2022. Malaysia, she said, has 178 public hospitals, 19 MOH hospitals, 74 private hospitals and one thousand seven hundred approved investigators. Humanity demands that we address unmet medical needs access to innovative treatments and transform health outcomes for patients through clinical trials. We have one stop centre for both sponsors and CROs. We ensure fast and accurate feasibility database. She also referred to budget negotiations and enquiries, legal enquiries besides regulatory and submission enquiries.
CRM as a Centre of Excellence organizes twelve weeks Foundation programme. There are three intakes per year. We have two trainers and one training consultant. We have centralized ethical review. The number of clinical research professionals is two hundred and it is growing. We have structured training on Good Clinical Practice which is supervised, secure and stable. Giving details of clinical trials completed she mentioned it included four hundred twenty six in oncology, two hundred forty eight in infectious diseases, one hundred twenty eight in paediatric, two hundred eleven in cardiovascular diseases and one hundred eleven in endocrinology. In 2016 we had one hundred forty two approved sites which has now increased to two hundred seventy one. We attract many global sponsored trials. We had 2572 sponsored research projects and it created three thousand fifty nine jobs. CRM gives approval of clinical trials in four to six weeks and ethical approval takes just thirty two calendar days. We are now striving for ASEAN initiative through industry sponsored clinical trials, she remarked.
Dr. Iftikhar Mahmood an independent consultant discussed New Drug Application- Regulatory and Scientific Aspects. In the next session Dr. Faize Bashir focal person National Bioethics Committee for Research at Health Research Institute NIH discussed role of NBC in advancing ethical efficiency while Dr. Akbar Fatouhi spoke about Iran’s Medical Research Ethics System.
Earlier in the morning session Dr. Babar Saeed Khan Director Clinical Trials Unit at NUMS talked about Pakistan Clinical Trials Landscape, Dr. Zainab Samad spoke on Disease Pattern in Pakistan and their impact on clinical trials, Dr. Bashir Hanif gave details of Pak Sehat a Mini Framingham of Pakistan which is a longitudinal cohort for cardiovascular diseases. Dr. Adeel Khoja, Dr. Abdul Basit and Dr. Shahid Pervez also discussed different aspects in this session. Clinical Proceedings of the Second Day of the Clinical Trials Summit to follow in the next issue. SAJ
