Guidelines for conducting ‘clinical trials’ relate to the following:

• Obtaining permission to start a clinical trial
• Registration of trial
• Obtaining consent of a trial participant
• Monitoring of a clinical trial
• Reporting of Serious Adverse Reaction (SAE)
• Compensation to be paid in case of SAE

It is mandatory to seek and obtain approval for any new clinical trial from the CDSCO (DCGI office). Proposal for new clinical trial has to be submitted to the CDSCO, which is then reviewed by a Technical Review Committee (TRC). Once approved by TRC the PI should submit the proposal to the Institutional Ethics Committee (IEC) approval.

Simultaneously, the clinical trial protocol must be registered at the ICMR Clinical Trial Registry www.ctri.in . It is mandatory to have CTRI registration for the trial to be granted operative approval as a project in Research section.

In addition to obtaining written informed consent, audio-visual recording of the consent taking process is a must, especially for the vulnerable population be done, confidentiality must be maintained while taking consent and such recordings must be preserved.

All clinical trials should be monitored. A data safety monitoring board (DSMB) should be created at institution level to monitor adverse events occurring in a clinical trial. It is the responsibility of the investigator to report all adverse events in a clinical trial, in a time bound manner to the IEC and DSMB. The DSMB also reports its findings to the IEC on its own.

The Investigator has to report all serious and unexpected adverse events to the CDSCO, the Sponsor or his representative whosoever had obtained permission from the CDSCO for conduct of the clinical trial and the Ethics Committee, within 24 hours of their occurrence as per the desired format. The IEC determines the causality of the SAE as to whether it is related to the investigational drug or not. The IEC gives its opinion to the expert committee constituted by the Ministry of Health. The expert committee also determines if the SAE is causally related to the drug and recommends suitable compensation based on a formula. The DCGI then directs the sponsor to pay compensation to the participant or to his/her relative.

In case of serious adverse events of death, the reports are examined by an independent expert committee constituted by DCGI to determine if the cause of death is due to following reasons, (which are considered as clinical trial related death) :

• adverse effect of investigational product(s);
• violation of the approved protocol, scientific misconduct or negligence by the Sponsor or his representative or the investigator;
• failure of investigational product to provide intended therapeutic effect;
• use of placebo in a placebo-controlled trial;
• adverse effects due to concomitant medication excluding standard care, necessitated as part of approved protocol;
• for injury to a child in–utero because of the participation of parent in clinical trial;
• any clinical trial procedure involved in the study

The expert committee also recommends the quantum of compensation to be paid by the sponsor or his representative and gives these recommendations to CDSCO, who   consider the recommendations of the expert committee and finalize the cause of death and the quantum of compensation in such cases, within three months of receiving the report of SAE of death.

In cases of serious adverse event other than death, CDSCO determines the cause of injury, if the cause is found to be due to any of the reasons mentioned above (as in the case of death) , the injury is considered as clinical trial related injury. However, CDSCO has an option to constitute an independent expert committee, wherever considered necessary, to examine such serious adverse event. In case of clinical trial related injury, CDSCO also determines the quantum of compensation within three months of receiving of the SAE. In case of clinical trial related injury or death, the Sponsor or his representative concerned shall pay the compensation as per the order of CDSCO within thirty days of the receipt of such order.

In view of mandatory requirements for conducting clinical trials including the ongoing trials, all investigators must apprise themselves of the existing rules and regulations related to clinical trials (https://cdsco.gov.in/opencms/opencms/en/Clinical-Trial/clinical-trials/). At the Institute they need to comply with the following:

• The investigator must obtain necessary regulatory approvals e.g. from DCGI and the IEC before starting any clinical trial.
• The trial must be registered at the ICMR clinical trial registry website. (ctri.nic.in)
• The investigators must undertake audio-visual recording of the consent from the participants. The recordings must be preserved, and confidentiality of the subject must be maintained. (CMET provides technical assistance in this matter)
• The investigator must report any expected SAE or suspected unexpected serious adverse reaction (SUSAR) to the IEC (SAE committee) within 24 hours of its occurrence.
• The investigators must periodically submit the progress of their trials to the IEC for the purpose of monitoring of the trial.
• The investigator must make adequate arrangements for compensation of the subjects either through the sponsor or insurance. If the trial is investigator initiated, then the investigator should make arrangement for providing compensation. Third party insurance for SAE and professional indemnity insurance for research staff involved in trial ensure adequate compensation mechanisms.

To simplify processes and maintain uniformity in project management on the part of the research section following standard operating procedures are suggested for initiation of a clinical trial, especially those that are industry funded or ae a part of the larger multi-site trials:
The sponsor should write to the proposed PI (faculty/scientist) indicating its intent to conduct such a research project and then the PI should seek approval of the Dean (Research) to conduct the research project in a specified project request format.  The final approval will be given by the Director, AIIMS.
The Research Section will give initial go ahead for the research project after satisfying the minimum criteria and ask the PI to get relevant ethics approval and other requisite clearances.
As per the DCGI norms, a PI cannot conduct >3 clinical trials at a given point of time.

• The project request format with a check list will consist of the following:
  • Name of the Project Investigator/designation/department
  • Name of Co-investigator/designation/department
  • Title of the project
  • Sponsoring funding agency
  • Total budget
  • Brief summary of the project (250 words)
  • Number of ongoing clinical trials with the PI
  • Ethics approval taken/applied for/to be taken
  • Expected outcome of the study
• The Research Section will grant a temporary CT number to this request for trial/project on a priority.
• The Applicant Investigators for the trial/project are permitted to negotiate the terms condition of the trial/project with the funding agencies on behalf of Institute.
• The Applicant Investigators will also be permitted to attend “Investigators’ Meeting” with regard to development of methodologies and protocol of the clinical trial/project, even before the award of the funding.
• The Applicant Investigators are not permitted to receive travel sponsorship and hospitality from the private funding agency directly but only through the Research Section on the basis of a proposal/Research Project. The Research Section will receive fund from the sponsor of clinical trial/project and reimburse travel cost of the Applicant Investigators for any consultation- processes before funding.  Any such agency/private firm must transfer such an amount to AIIMS that may be required for any such travel(s) by applicant investigator(s) prior to the actual award of the grant for the Research Project.  This amount will be kept for such purpose under a Temporary Code (or Account) and if the Research grant finally materialises, the Code No. and the account will continue for research in the project.
• Ethical Clearance: The Applicant Investigators in consultation with the funding agency will obtain clearance from the Institute Ethics Committee after the Research protocol is finally made by the Applicant Investigators.
• Mandatory clearances: The Applicant Investigator in consultation with the funding agency will obtain all other clearances from agencies such as DGCI etc. as may be deemed necessary.
• Clearance from Health Ministry Screening Committee: The Applicant Investigator in consultation with the funding agency will obtain clearances from the Health Ministry Screening Committee in case the trial/project is an international trial/project. Projects conducted by Indian clinical trial/project agencies will also require HMSC clearance in case the primary sponsor happens to be an international funding agency. The AIIMS Research Section also assists in the process.
• Registration with Clinical Trial Registry of India. The Applicant Investigator will get the trial registered with Clinical Trail Registry of India.
• Memorandum of Understanding and Initiation of the trial: After all the above clearances are received, a MOU will be signed between AIIMS for the Applicant Principal Investigator and the funding agency. The Applicant Investigators will be appointed as Principal Investigator and Co-Investigators and they will approach the Research Section for administrative approval for starting the project. The Research Section will provide a code number to the project after obtaining administrative approval from competent authority.
• Appointment of project staff: The Principal Investigator will appoint project staff as per the norms followed at AIIMS in consultation with Research Section.
• Project Expenditure: The Principal Investigator will follow budget heads as sanctioned by the funding agency and will only be allowed to transfer funds from one head to another with approval of the funding agency, e.g. (travel, manpower and equipment/consumables etc.).
• Reporting: The Principal Investigator and Co-Investigators will submit a six-monthly progress report to Institute Ethics Committee. They in addition will report any serious adverse event (SAE) to the Institute Ethics Committee within 24 hours of occurrence.
• Completion of the trial/project: At the end of the trial the Principal Investigator and Co-Investigators will submit a copy of the final report and a summary of the project (for Research Review Committee) in the prescribed format for closure of the project.
• Utilization of unspent balance: The Principal Investigator may refund the unspent balance to the funding agency. However, in case he/she desires to utilise the unspent balance for piloting another research project, an approval will be necessary from the Director, AIIMS. However, in no case the unspent fund will be utilized for travel or any other personal benefit, unless provided for in the project protocol.  The unspent money  could also be donated to AIIMS for any other purpose such Poor Patient-care or Research with a written letter from the funding firm/industry.  The Director, AIIMS in consultation with Research Section will take a final decision on such unspent money for any other welfare measures in AIIMS.
• Administrative charge: The Research Section will levy an administrative charge as applicable from the funds received in the project.
• For investigator driven clinical trials/projects, the expression interest will be submitted by the interested faculty member. Rest of the steps will remain the same.