|Year : 2022 | Volume
| Issue : 2 | Page : 47-50
Importance of ethics committees in diabetes-related clinical research in India
Ravindra B Ghooi1, Shailesh R Deshpande2
1 Scientia, Clinical Services, Pune, Maharashtra, India
2 Department of Education, Chellaram Diabetes Institute, Pune, Maharashtra, India
|Date of Submission||16-Jun-2022|
|Date of Acceptance||17-Jun-2022|
|Date of Web Publication||16-Jul-2022|
Shailesh R Deshpande
Chellaram Diabetes Institute, Lalani Quantum, Pune - Bengaluru National Highway, Bavdhan (BK), Pune - 411 021, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Ghooi RB, Deshpande SR. Importance of ethics committees in diabetes-related clinical research in India. Chron Diabetes Res Pract 2022;1:47-50
|How to cite this URL:|
Ghooi RB, Deshpande SR. Importance of ethics committees in diabetes-related clinical research in India. Chron Diabetes Res Pract [serial online] 2022 [cited 2022 Oct 5];1:47-50. Available from: https://cdrpj.org//text.asp?2022/1/2/47/351232
Diabetes carries a significant global burden. Worldwide, 537 million adults have diabetes, a figure projected to rise to 783 million by 2045. Diabetes has also emerged as an important public health problem in India, with an estimated 74.2 million adults having diabetes, likely to reach 124.9 million by 2045.
Diabetes, for most patients, is a lifelong condition, with the propensity for affecting multiple body organs through various complications, resulting in significant morbidity, increased health-care expenditure, poor quality of life, and premature mortality.
While early intervention through diet and lifestyle modification can certainly bring about improvement, the majority of patients would require medical therapy. A wide range of drugs is available today for the physician to aid in the management of diabetes, including oral antidiabetic drugs and injectables, especially insulin. It is worthwhile to note here that anti-diabetic drugs are among the most selling drugs in India.
Clinical trials have played a critical role in defining effective therapies for diabetes mellitus and the different stages of its myriad complications. Equally important, ineffective therapies have been discarded based on controlled clinical trials. The net effect of clinical trials has been an expansion of life span and an improvement in quality of life.
In addition to the trials for drugs, studies on diet and exercise ‒ many of them being preventive trials, as well as on newer diagnostic tests are also being carried out worldwide, with a significant number of them underway in India.
Since 2005, there has been an increase in outsourcing of clinical trials in India and our country has become a hub for clinical trials. This is due to the presence of well-qualified doctors and staff, a large patient pool, trained support in technology, and low drug development costs.
All trials in India need to be registered on the government portal: the Clinical Trials Registry ‒ India. For conducting a clinical trial, permission is required from the regulator and from the ethics committee (EC) of the sites where the trial is to be conducted. The principal role of an EC is to protect the rights, safety, and well-being of participants in clinical trials, in other words, to provide ethical oversight to clinical research.
The principles of ethics rest on the four pillars of autonomy, beneficence, justice, and nonmaleficence. Recently, two more pillars have been added, which include confidentiality and honesty. This is achieved by reviewing the study protocol and related documents for scientific and ethical validity. In India, this responsibility lies with the institutional ECs. The drug regulator's office in India ‒ the Central Drug Standards and Control Organization (CDSCO) has the responsibility of overseeing new drug development. Headed by the Drugs Controller General of India, it also has the responsibility of ensuring that the ECs discharge their duties, as required.
The ECs in India are required to be registered with the CDSCO before they can review and approve clinical trials. The regulator thus has indirect control and ensures that all clinical research is conducted while protecting the rights and the well-being of trial participants. Currently, there are over 1700 ECs, that review clinical trials, bioavailability (BA), and bioequivalence (BE) studies in the country.
The ethical issues in clinical trials related to diabetes are not fundamentally different from those in other trials. Nevertheless, some issues merit a discussion here.
One is the debate concerning the use of a placebo in diabetes-related trials as opposed to the available standard of care. The World Medical Association's Declaration of Helsinki ‒ Ethical Principles for Medical Research involving human subjects has stated its position on the use of a placebo that the benefits, risks, burdens, and effectiveness of a new intervention must be tested against those of the best-proven intervention(s), except in some specific circumstances.
As per the declaration, the use of placebos as comparators is not encouraged, but some researchers vouch for placebo-controlled trials in type 2 diabetes. They argue that placebos are ethical, even for conditions where effective treatment already exists, provided that patients are not harmed and are fully informed. Occasional placebo-controlled trials in diabetes are conducted in some countries like the United States, which does not accept the Declaration of Helsinki as a binding guideline.
It becomes incumbent on the ECs to carefully evaluate any placebo-controlled trial involving subjects with type 2 diabetes before approval.
Another issue relates to posttrial access for the research subjects. The Declaration of Helsinki (op. cit.) states that in advance of a clinical trial, sponsors, researchers, and host country governments should make provisions for posttrial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process. The New Drug and Clinical Trial Rules of 2019 include posttrial access as a requirement in clinical trials, although with some conditions.
This applies particularly to diabetes-related trials, as many of the newer drugs, including insulins and other therapies such as the artificial pancreas are costly. The ECs need to check while reviewing the study protocol that posttrial access is ensured for the trial subjects, as per the law.
The provision of rescue medication in clinical trials is necessary to prevent any harm to the subjects if their condition worsens. This can, however, complicate the analysis of trials. In type 2 diabetes trials, patients receive glucose-lowering rescue medications continuously for the remaining trial duration, if one of several markers of glycemic control exceeds prespecified thresholds. This may mask differences in glycemic values between treatment groups because it will occur more frequently in less effective treatment groups. It is possible to estimate the effect of rescue medication on the trial results through statistical methods like simulation.
The members of the EC, particularly the scientific members, need to be aware of the rescue medication available for the research subjects and deliberate on the statistical methods available to address any effects on the trial outcomes.
One of the functions of the ECs is to ensure that the trial participants receive an adequate and timely supply of the study drug(s). Concerns regarding this aspect have been raised in the context of clinical research on diabetes and hypertension in sub-Saharan Africa.
Although such concerns were not much prevalent routinely in India, they did surface during the time of the COVID-19 pandemic, during which various strategies to ensure the safety of the trial participants and continuance of treatment, for instance, alternative drug dispensing methods, had to be devised. The Indian Council of Medical Research (ICMR) formulated guidelines for the ECs to function capably during the pandemic.
Apart from drugs, surgical options like bariatric surgery exist for the difficult-to-manage cases of diabetes, and particularly with obesity. Issues specific to research in such surgical therapies exist and will have to be considered by the ECs accordingly. Novel treatments will entail newer ethical issues, and the ECs will have to gear up to address the ensuing challenges.
Trials on complementary and alternative medicine in diabetes management are seeing a rising trend in India. The ethical framework for such studies is not as well defined as that for modern medicine, and such treatments pose their own ethical issues. Nevertheless, the pillars of ethics alluded to above are equally relevant to such studies. The ECs need to be mindful of the potential issues and make decisions based on the merits of the study.
A number of diabetes-related studies are now employing apps and/or devices for diagnosis, monitoring, and treatment. Besides convenience, new technological innovations also afford a chance for timely intervention in managing the patient's condition. However, such technologies bring with them their own challenges in the form of data security, potentially jeopardizing the patient's privacy and confidentiality.
It has been remarked that there are currently no procedures or standard practices for developers of mobile medical apps to assure data integrity and security. In such a scenario, the EC needs to carefully scrutinize the protocol if it mentions the necessary safeguards for protecting the subject's privacy and confidentiality.
Some of the studies on diabetes involve vulnerable subjects. Examples include children with type 1 diabetes – where assent from older children becomes necessary, elderly patients with type 2 diabetes, and studies on gestational diabetes mellitus that involve pregnant women. In all such cases, the EC should ascertain that the protocol and other documents adequately address the relevant ethical concerns and meet the applicable regulatory requirements for such studies.
The ECs also need to set up and implement a system of periodic monitoring, including site visits, to ensure that the research is being conducted as per the approved protocol, and following all the ethical guidelines. Any protocol deviations or violations should be noted and corrective action is recommended by the EC.
It has to be considered here that the ECs are made up of independent people coming from varied backgrounds who need to be trained in research ethics. To ensure the efficient functioning of the ECs, adequate training of the EC members is essential. Medical research and ethics are both continually evolving fields; hence, the training also needs to be continuous, and on regular basis.
Many of the ECs do have well-trained members and are protecting research participants well. There is a third-party verification of EC competencies available, but it is not mandatory, and only a small fraction of the total ECs has opted for accreditation. There is a need for more ECs to opt for this accreditation so that participants are protected uniformly all over the country. Unless research participants are assured adequate protection, they will not volunteer for trials. Since protecting them is a responsibility of ECs, the competency of EC members has far-reaching consequences, for investigators, trial sites, and the country at large.
The New Drugs and Clinical Trial Rules 2019 speak of mandatory training of EC members. Considering the large number of ECs across the country and the turnover of members, it is a difficult task to effectively train all the members. The government needs to ensure that EC members in the country are well trained to carry out their responsibilities. However, to our understanding, no organization is capable of handling this amount of work, hence, the training needs to be outsourced.
For this purpose, the government can adopt the “train the trainer” model, wherein a few persons in each city/state can be identified and trained, and they can be authorized to impart training to all the ECs in that region. When all the members are well trained, the ECs will be able to fulfill their important responsibilities. This will ensure participant protection and the growth of clinical research in the country.
| References|| |
International Diabetes Federation. IDF Diabetes Atlas. 10th
ed. Brussels, Belgium: International Diabetes Federation; 2021.
Nathan DM. Clinical review 146: The impact of clinical trials on the treatment of diabetes mellitus. J Clin Endocrinol Metab 2002;87:1929-37.
Maiti R, Raghavendra M. Clinical trials in India. Pharmacol Res 2007;56:1-10.
Nandra R, Brockie AF, Hussain F. A review of informed consent and how it has evolved to protect vulnerable participants in emergency care research. EFORT Open Rev 2020;5:73-9.
Department of Health, Education, and Welfare; National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont report. Ethical principles and guidelines for the protection of human subjects of research. J Am Coll Dent 2014;81:4-13.
Thatte UM, Marathe PA. Ethics committees in India: Past, present and future. Perspect Clin Res 2017;8:22-30.
] [Full text]
World Medical Association. World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310:2191-4.
Misbin RI. Placebo-controlled trials in type 2 diabetes. Diabetes Care 2001;24:773-4.
Holzhauer B, Akacha M, Bermann G. Choice of estimand and analysis methods in diabetes trials with rescue medication. Pharm Stat 2015;14:433-47.
Shayo E, Van Hout MC, Birungi J, Garrib A, Kivuyo S, Mfinanga S, et al.
Ethical issues in intervention studies on the prevention and management of diabetes and hypertension in sub-Saharan Africa. BMJ Glob Health 2020;5:e002193.
Torres AJ, Cano-Valderrama O, Domínguez-Serrano I. Ethical issues in bariatric surgery. In: Ferreres AR, editor. Surgical Ethics: Principles and Practice. Switzerland: Springer Nature Switzerland AG; 2019. p. 295-303.
Miller FG, Emanuel EJ, Rosenstein DL, Straus SE. Ethical issues concerning research in complementary and alternative medicine. JAMA 2004;291:599-604.
Treacy C, McCaffery F. Data security overview for medical mobile apps. Assuring the confidentiality, integrity and availability of data in transmission. Int J Adv Secur 2016;9:146-57.
Ghooi RB. Need for revision – EC process, members' training and compensation formula in new drugs and clinical trials rules 2019. Perspect Clin Res 2022;13:129-31. [Full text]