Clinical Trial vs Biomedical Research: Do we need a sorting hat?
New Drugs and Clinical Trial approval regulations 2019 have made a distinction between clinical research and biomedical research and the ethics Committees (EC) to approve the same.
To approve clinical research, we need to approach an Ethics Committee (EC) formed as per CHAPTER III- ETHICS COMMITTEE FOR CLINICAL TRIAL, BIOAVAILABILITY AND BIOEQUIVALENCE STUDY
To approve biomedical and health research, we need to approach an EC formed as per CHAPTER IV ETHICS COMMITTEE FOR BIOMEDICAL AND HEALTH RESEARCH. I will call them Ch3 and Ch4 for ease of typing
A definition has also been provided for Biomedical research: “biomedical and health research” means research including studies on basic, applied and operational research or clinical research, designed primarily to increase scientific knowledge about diseases and conditions
(physical or socio-behavioral); their detection and cause; and evolving strategies for health promotion, prevention, or amelioration of disease and rehabilitation but does not include clinical trial.
Why am I stating these facts?
I happen to be the chairman of a local EC. While discussing an observational study with some colleagues, who work for other ECs, it was suggested that I should register my EC under NAITIK too, since observational studies will fall under Ch 4. Just as we have to apply on the SUGAM portal for registering an EC under Ch 3, one registers on the NAITIK portal to register a study under Ch4.
I objected saying that any study where an intervention happens in a patient has to reviewed under Ch 3.
I was informed that only studies under the new drug category will come under Ch3, all the rest coming under Ch4. In case of doubt one has to enquire with the Drugs Controller’s office to receive a clarification.
I set about reading the new drug regulation and the frequently asked questions. I found the following that may have influenced my friends. Many decisions seem to revolve around the definition of a new drug mentioned in these regulations
In addition to prescribing the need for two types of ECs, the new regulation also mentions that “Any institution or organisation which intends to conduct biomedical and health research shall be required to have an Ethics Committee to review and oversee the conduct of such research as detailed in National Ethical Guidelines for Biomedical and Health Research Involving Human Participants.”
A couple of questions and responses from the FAQs are as under
Whether compensation, medical management in case of injury or death of trial subjects is applicable in case of academic clinical trial?
The academic clinical trial shall be required to be conducted in accordance with the approved clinical trial protocol, ethical principles specified in National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, notified by the ICMR with a view to ensuring protection of rights, safety and wellbeing of trial subject during conduct of such clinical trial. Therefore, ethical principles including compensation, medical management in case of injury or death etc. as prescribed in National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, notified by the ICMR are applicable for academic clinical trials.
Whether systematic clinical study of a drug (not covered under the definition of new drug) in human beings requires permission from the CLA?
……………. Therefore, in case the drug is truly not a new drug, in respect of composition, dosage form, indication, use, patient population etc. no permission from CLA may be required for conduct of such study of such drug in human beings. However, if such study is covered under category of observational study or non-interventional study, the same will be regulated as per the Fifth Schedule of the New Drugs and Clinical Trials Rules, 2019. Study of such drug in human beings if covered under the definition of Biomedical and Health Research, the same will be regulated as per the regulatory provisions prescribed under Chapter IV of the New Drugs and Clinical Trials Rules 2019 shall be applicable
The said ICMR guidelines “National Ethical Guidelines for Biomedical and Health Research
Involving Human Participants” has a chapter dedicated to “Clinical trials of drugs and other interventions”, and separate ones addressing “Public health research” and “Social and behavioural sciences research for health”
The combined definition of public, social and behavioural research is close to what is envisaged for Ch4 studies.
In the chapter on clinical trials of drugs, under phase IV studies it lists the following
In the case of Phase IV studies, the following are some examples of studies
that require EC approval:
(i) Phase IV clinical trials
(ii) Outcome research
(iv) Data that is used to answer any research question
(v) New use/route/dose/dosage form/combination/regimen of a marketed drug for non-commercial purpose such as academic research
In addition to EC approval, a Phase IV clinical trial on drugs with a market authorization of less than 4 years requires regulatory approval (CDSCO). (Again a reference to “new drug” but clearly demarcates the jurisdiction of the EC and the CDSCO)
In the ICMR guidelines, there is a general requirement given for an EC, but there is also a mention that if clinical trials are being reviewed, the basic medical scientist should be a preferably a pharmacologist; something close to Ch3 ECs
So, my simple segregation would be:
Any clinical study in whatever phase, involving patients where data is collected through investigations, scales or observation, after an intervention with drugs or otherwise will come under Ch3.
Studies on healthy individuals as in vaccine or Bioequivalence studies would also fall under Ch3
Those involving disease patterns, management, prevention could come under Ch4 as in a study establishing the prevalence of a disease in a given population through a screening test
But there would be fence sitters too.
Let’s say a serum marker is being ascertained in COVID patients. Since a patient is involved, this could come under CH3, but if the same was studied in cases who have recovered from COVID, this could go under CH4. But since it involves use of the individuals body fluids it may also fit under Ch3
Let me put forth some scenarios
• Genotyping patients to identify fast and slow metabolisers after administration of a drug would go to Ch3 because a patient and drug are involved, and one also needs permission for genotyping
• Genotyping in general population to identify prevalence of some disease marker would be under Ch4 since no patient or drug is involved
• A psychologist wishing to measure anxiety levels in COVID patients admitted to a hospital would be referred to Ch3 since a patients are involved
• A psychologist wishing to measure anxiety levels in COVID recovered cases in the population would fall under Ch4 since no patient or drug is involved
Well, I am certainly going to ask the licencing authority for a clarification (hope I get one with examples and not the routine nebulous response), but I do hope I receive their response on this blog itself. I also seek comments from my colleagues.
If nothing works, I will have to use the Harry Potter kind of “sorting hat” to decide.
• G.S.R.227(E) New Drugs and Clinical Trials Rules, 2019
• Frequently Asked Questions (FAQs) on New Drugs and Clinical Trials Rules
• National Ethical Guidelines for Biomedical and Heal th Research Involving Human Participants – ICMR
Dr Vishwas Sovani (November 2020)