ICMR tightens regulations for biomedical research

Human participation in biomedical research should be based on the principle of essentiality whereby due consideration of all alternatives in the light of existing knowledge is taken before deciding that use of human participants is essential for the proposed research. This should also be duly vetted by an ethics committee (EC) independent of the proposed research, as per the revised regulations of the Indian Council of Medical research (ICMR).

The council said human participation in biomedical research should be based on informed consent and the principle of voluntariness should give due respect for the right of the participant to agree or not to agree to participate in research, or to withdraw from research at any time, so that the participants' rights are safeguarded.

Research participants should be equitably selected so that the benefits and burdens of the research are distributed fairly and without arbitrariness or discrimination. Sufficient safeguards must also be taken to protect vulnerable groups, it said.

Research must be planned and conducted in a way as to avoid creation or deepening of social and historic divisions or in any way disturb social harmony in community relationships.

Research groups must ensure privacy and confidentiality of potential participants whereby her/his identity and records are kept confidential and access is limited to only those authorised. This should be observed in all cases except in cases where for valid scientific or legal reasons as the right to life of an individual supersedes the right to privacy of the research participant.

While conducting research with stored biological samples or medical records/data, coding or anonymisation of personal information is important and access to both samples and records should be limited.

Due care must be taken by all stakeholders (including but not limited to researchers, ECs, sponsors, regulators) at all stages of the research to ensure that the risks are minimised and appropriate care and compensation is given if any harm occurs.

It must also be ensured that those entrusted with research have professional competence and have appropriate and relevant qualification, experience and/or training to monitor the research process throughout and evaluate results.

Research should be carried out in a transparent manner and the organisers should bring the outcome of the research to the public domain through registries, reports and scientific and other publications while safeguarding the right to privacy of the participants.

Stakeholders involved in research should disclose any existing conflict of interest and manage it appropriately. The research should be conducted in a fair, honest, impartial and transparent manner to guarantee accountability. Related records, data and notes should be retained for the required period for possible external scrutiny/ audit.

Principle of totality of responsibility whereby all stakeholders involved in research are responsible for their actions. The professional, social and moral responsibilities compliant with ethical guidelines and related regulations are binding on all stakeholders directly or indirectly.

Principle of environmental protection whereby researchers are accountable for ensuring protection of the environment and resources at all stages of the research, in compliance with existing guidelines and regulations.

Benefit-risk assessment
The social and scientific value of research should justify the risk, which is the probability of causing discomfort or harm anticipated as physical, psychological, social, economic or legal.

The researcher, sponsor and EC should attempt to maximize benefits and minimise risks to participants so that risks are balanced to lead to potential benefits at individual, societal and/or community levels.

The EC should assess the inherent benefits and risks, ensure a favourable balance of benefits and risks, evaluate plans for minimizing the risk and discomfort and decide on the merit of the research before approving it.

The EC should also assess any altered risks in the study at the time of continuing review.

Less than minimal risk: In this case the probability of harm or discomfort anticipated in the research is nil or not expected. For example, research on anonymous or non-identified data/samples, data available in the public domain, meta-analysis, etc.

Minimal risk: Probability of harm or discomfort anticipated in the research is not greater than that ordinarily encountered in routine daily life activities of an average healthy individual or general population or during the performance of routine tests where occurrence of serious harm or an adverse event (AE) is unlikely. Examples include research involving routine questioning or history taking, observing, physical examination, chest X-ray, obtaining body fluids without invasive intervention, such as hair, saliva or urine samples, etc.

Minor increase over minimal or low risk: Increment in probability of harm or discomfort is only a little more than the minimal risk threshold. This may present in situations such as routine research on children and adolescents; research on persons incapable of giving consent; delaying or withholding a proven intervention or standard of care in a control or placebo group during randomised trials; use of minimally invasive procedures that might cause no more than brief pain or tenderness, small bruises or scars, or very slight, temporary distress, such as drawing a small sample of blood for testing; trying a new diagnostic technique in pregnant and breastfeeding women, etc. Such research should have a social value. Use of personal identifiable data in research also imposes indirect risks. Social risks, psychological harm and discomfort may also fall in this category.

More than minimal risk or high risk: Probability of harm or discomfort anticipated in the research is invasive and greater than minimal risk. Examples include research involving any interventional study using a drug, device or invasive procedure such as lumbar puncture, lung or liver biopsy, endoscopic procedure, intravenous sedation for diagnostic procedures, etc.

Distributive justice
Efforts must be made to ensure that individuals or communities invited for research are selected in such a way that the benefits and burdens of research are equitably distributed.

Vulnerable individuals/groups should not be included in research to solely benefit others who are better-off than themselves.

Plans for direct or indirect benefit sharing in all types of research with participants, donors of biological materials or data should be included in the study, especially if there is a potential for commercialization. This should be decided a priori in consultation with the stakeholders and reviewed by the EC.

Payment for participation
If applicable, participants may be reimbursed for expenses incurred relating to their participation in research, such as travel related expenses. Participants may also be paid for inconvenience incurred, time spent and other incidental expenses in either cash or kind or both as deemed necessary (for example, loss of wages and food supplies).

Participants should not be made to pay for any expenses incurred beyond routine clinical care and which are research related, including investigations, patient work up, any interventions or associated treatment. This is applicable to all participants, including those in comparator/control groups.

If there are provisions, participants may also receive additional medical services at no cost.

When the LAR is giving consent on behalf of a participant, payment should not become an undue inducement and to be reviewed carefully by the EC.

Reimbursement may be offered for travel and other incidental expenses incurred due to participation of the child/ward in the research.

ECs must review and approve the payments (in cash or kind or both) and free services and the processes involved, and also determine that this does not amount to undue inducement.

Compensation for research-related harm
Research participants who suffer direct physical, psychological, social, legal or economic harm as a result of their participation are entitled, after due assessment, to financial or other assistance to compensate them equitably for any temporary or permanent impairment or disability. In case of death, participant's dependents are entitled to financial compensation. The research proposal should have an in-built provision for mitigating research related harm.

Ancillary care: Participants may be offered free medical care for non-research-related conditions or incidental findings if these occur during the course of participation in the research, provided such compensation does not amount to undue inducement as determined by the EC.

Conflict of interest
Conflict of interest (COI) is a set of conditions where professional judgement concerning a primary interest such as participants welfare or the validity of research tends to be unduly influenced by a secondary interest, financial or non-financial (personal, academic or political). COI can be at the level of researchers, EC members, institutions or sponsors.

If COI is inherent in the research, it is important to declare this at the outset and establish appropriate mechanisms to manage it.

Research institutions must develop and implement policies and procedures to identify, mitigate conflicts of interest and educate their staff about such conflicts.

Researchers must ensure that the documents submitted to the EC include a disclosure of interests that may affect the research.

ECs must evaluate each study in light of any disclosed interests and ensure that appropriate means of mitigation are taken.

COI within the EC should be declared and managed in accordance with standard operating procedures (SOPs) of that EC.