Clinical trials are the highest standard of research, representing meticulously planned experimental studies where an intervention (like a new drug, vaccine, or technology) is tested in humans. They are critical for advancing medical science but require strict adherence to regulatory and ethical guidelines.
1. The Clinical Trial Landscape in India
India has seen rapid growth in clinical trials, but also recent challenges due to regulatory reforms:
- Past Challenges: Delays in ethical and regulatory approvals, concerns about the quality of ethical review, restrictions on sample shipment and data transfer, and a perceived lack of certified and trained investigators.
- Regulatory Reforms:
- Compensation: Strict regulations mandate specific calculations for compensation to trial participants.
- Audio-Visual (AV) Recording: Mandated for the informed consent process in Investigational New Drug (IND) trials to ensure accountability and transparency, provided confidentiality is protected.
2. Mandatory Approvals Before Starting a Trial
Any clinical trial requires a minimum of three levels of clearance:
| Review Type | Reviewing Body | Focus |
| Scientific Review | Institutional Scientific Advisory Committee | Is the research question sound? Is the study design appropriate? Are the methods accurate and correct? |
| Ethical Review | Institutional Ethics Committee (IEC) / National Ethics Committee | Is the safety and welfare of research participants adequately protected (Do No Harm)? This review is critical. |
| Regulatory Review | CDSCO (Drugs Controller), Health Ministry Screening Committee, Genetic Engineering Approval Committee (GEAC) | Ensures compliance with specific national laws related to new drugs, foreign funding, or the use of genetically engineered products. |
3. Key Ethical Issues in Clinical Trials
Because trials involve manipulating the environment (experimentation), ethical protections are paramount:
- Ongoing Monitoring: Initial approval is insufficient; the IEC must monitor the trial all throughout to ensure participant safety.
- Informed Consent: Every participant must sign an informed consent form.
- Community Engagement: Engage the community (doctors, program managers, political leaders) to ensure the intervention is culturally acceptable and receives support.
- Post-Trial Support: A mechanism for providing follow-up care or post-trial access to the successful intervention must be planned and outlined in the protocol.
- Use of Placebos: Generally justifiable only when no comparable intervention (drug or vaccine) currently exists for that disease.
- Confidentiality: Must be rigorously protected, as participants may fear family members or others knowing about their participation.
4. The Conduct and Procedures of a Trial
A. The Informed Consent Procedure
This is often a multi-step procedure where investigators carefully explain the study, answer all questions, and ensure the participant’s understanding.
- Documentation: A duplicate copy must be signed; one copy is kept by the participant.
B. Trial Adherence
- Screening: A formal process (interview, exam, sampling) to ensure participants meet strict inclusion and exclusion criteria.
- GCP Adherence: Investigators must follow Good Clinical and Laboratory Practice (GCP) rigorously (e.g., enrolling as defined, using defined procedures, adhering to visit schedules).
- Intervention Adherence: Systems must ensure participants regularly take the drug/vaccine or adhere to the protocol, and attend follow-up evaluations to prevent missing key data points (e.g., vaccine antibody levels).
- Multi-Centric Trials: Requires standardization of protocols and periodic training across all sites to mitigate variations in procedures.
C. Safety and Monitoring
- Independent Monitoring: An agency, usually employed by the sponsor, ensures adherence to GCP, dispensing, and consent procedures with a third-party view.
- Adverse Event (AE) Reporting: Safety assessments are built-in. AEs (which can be clinical, laboratory, or social/familial) and Serious Adverse Events (SAEs) must be timely reported to regulatory authorities, sponsors, and IECs.
- Trial Stoppage Rule: Must be defined a priori. Generally, a predetermined number of SAEs (e.g., three) triggers a review by an independent Data Safety Monitoring Board (DSMB) to decide whether the trial should continue.
- Reimbursement vs. Compensation: Reimbursement is for time lost, travel, and expenses; compensation is for trial-related injury. Reimbursement must not be so large as to act as a coercive incentive.
5. Impediments to Clinical Trials
Clinical trials are difficult to conduct due to challenges at both participant and provider levels:
| Level | Common Impediments |
| Patient/Volunteer | Lack of awareness, lack of access, mistrust, suspicion, fear, and concerns about fees. |
| Health Care Provider | Lack of awareness, unwillingness to lose control of patient care (referral fear), belief that standard therapy is best, and administrative burdens. |
Conclusion: Clinical trials, especially Randomized Controlled Trials (RCTs), are the only way to test new drugs, vaccines, and technologies. They must be supported and carried out with the highest possible quality adherence.
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