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|Year : 2013 | Volume
| Issue : 4 | Page : 323--324
Regulatory changes in conduct of clinical trials: A need for review
Department of Pharmacology, Institute of Postgraduate Medical Research and Education, Kolkata, West Bengal, India
Department of Pharmacology, Institute of Postgraduate Medical Research and Education, Kolkata, West Bengal
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Chatterjee S. Regulatory changes in conduct of clinical trials: A need for review.Indian J Pharmacol 2013;45:323-324
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Chatterjee S. Regulatory changes in conduct of clinical trials: A need for review. Indian J Pharmacol [serial online] 2013 [cited 2019 Nov 13 ];45:323-324
Available from: http://www.ijp-online.com/text.asp?2013/45/4/323/114990
The conduct of clinical trials in India has been critically reviewed at national and international platforms. The media outcry over trials being conducted unethically, gross negligence of the sponsor and its representatives to provide the free medical treatment and adequate compensation to subjects for trial related death(s) and injuries have negatively impacted on the industry. Much of what has happened is unfortunately the aftermath of unsatisfactory performance of all stakeholders of clinical trials, i.e., the sponsor, investigator, Ethics Committee and the regulatory authority. Accordingly, Central Drugs Standard Control Organization (CDSCO) introduced several amendments in the Schedule Y of drugs and cosmetic rules with a view to regulate the quality of trials conducted in India. All stakeholders of clinical trials should welcome these recent amendments as this is a sincere attempt to improve the quality of clinical trials and to ensure that the rights, well-being and safety of trial subjects are upheld. The salient notifications include: 
Compensation in case of injury or death during the clinical trials (the new rule 122 DAB)Essential and additional elements to be included in a study subject's Informed consent documentResponsibilities of the sponsor, investigator and Ethics Committee Serious adverse event (SAE) definition and revised reporting timeframes for SAE.
In addition, other steps like mandatory registration of Ethics Committees, contract research organizations and registration of regulatory trials with Clinical Trial Registry of India are steps in the right direction. However, there are concerns regarding the rationale and implementation of several clauses ,,, that merit a critical evaluation:
Entitlement for financial compensation for injury arising due to: "Adverse effect of investigational product(s), use of placebo in the placebo controlled trials or failure of investigational product to provide intended therapeutic effect" is a matter, which warrants further discussion and debate. Clinical research is often exploratory in nature and is undertaken to test a hypothesis when there is a lack of adequate knowledge in the said domain. This clause if implemented in its present form will be a deterrent to early phase clinical trials (Phase 1 and 2). Therefore, a clarification of what is meant by "intended therapeutic effect" is required as this clause essentially undermines the spirit of science. Similarly, the inclusion of a placebo arm in clinical trials is scientifically rational when there is non-availability of an active comparator or in diseases with a high placebo reactor rate. Therefore, compensation for any injury to subjects participating in a placebo controlled trial due to lack of therapeutic effect makes little sense. Finally, compensation for adverse effects of an already approved marketed control drug may not be made mandatory. In this context, the guidelines of the Association of the British Pharmaceutical Industry has recommended that "Compensation should be paid when, on the balance of probabilities, the injury was attributable to the administration of a medicinal product under trial or any clinical intervention or procedure provided for by the protocol that would not have occurred, but for the inclusion of the patient in the trial." , The CDSCO should critically review this clause and consider modifications in these lines.It is envisaged that the applicability of this compensation clause for all types of trials including academic, institutional or investigator initiated trials will have a significant negative impact on trials undertaken by post-graduate students/fellows as a part of their doctoral curriculum. A large number of investigator initiated trials are conducted in resource limited settings and most host institutes (except the premier institutions) may not be able to provide the corpus funds for such compensation. Although, we appreciate the logic behind the inclusion of all trials (for a trial subject it hardly matters whether the sponsor is a pharmaceutical company or government funding agency or the investigator himself), in reality it will be difficult to implement this clause in resource limited settings. Hence, for non-commercial, investigator initiated postmarketing trials waiver of some of these provisions would be beneficial. Otherwise interventional studies will become the monopoly of large pharmaceutical companies while others will have to address their research zest only through observational studies.The clause, which states that free medical treatment has to be provided in case of "any injury occurring to the clinical trial subject" and financial compensation over and above any expenses incurred on medical management of the subject for "injury that is related to the clinical trial" needs attention. The term "injury" in a clinical trial has to be specifically defined since the information stated in the said rule is incomplete. Does it mean all types of adverse events pertaining to the investigational product(s) irrespective of its relatedness, serious and non-serious, expected and unexpected? If free medical care has to be provided for any injury occurring to the clinical trial irrespective of its relatedness to the investigational products then such a clause has the potential to serve as strong inducement for subjects to participate in trials for diseases with have a high background rate of morbidity. Therefore, clarifications regarding this clause are needed.The role and responsibility of the Institutional Ethics Committee (IEC) has been enhanced many fold. It is appreciated by all that the IEC functions to safeguard the rights, safety and well-being of trial subjects. Majority of the IECs in India merely function as bodies for according approval for trials and very few have the infrastructure to critically review ongoing trials. From a practical standpoint, inducting knowledgeable and motivated persons as members of the IEC is becoming an increasingly difficult task and with the enormous responsibilities bestowed on the IEC by the regulatory authority, several members are opting out from such committees. In addition, the requirement of the IEC to review and report all serious and unexpected SAE to the licensing authority and the expert committee (in case of SAE leading to death) within 21 calendar days of its occurrence is a very short timeline. In view of the redefined role and responsibilities of the IEC, several full time employed members need to be inducted to achieve the goals set forth by the regulatory authority. This may not be practical.The area of the greatest concern pertaining to unethical practice is the informed consent taking process and its documentation. This has led to stringent rules being put forth to curb such unethical practice. However, considering the diverse educational and social status of our population, few trial subjects have the motivation or interest to go through the information given in the "patient information sheet" of the informed consent documents despite detailed discussion with them. It is also difficult for a trial subject to enlist the name of the nominee(s) in the informed consent form. This will overtly or covertly lead to investigators giving a preference for including a literate study population, which goes against the principle of natural justice.
To summarize, we pharmacologists involved in the clinical trials in various capacities (investigator, IEC member, regulatory authority representative), agree in principle with the recent amendments to the Schedule Y, but humbly suggest that modification of some of the clauses of the rule 122 DAB are deemed essential for the benefit of all stakeholders of clinical trials.
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