|Year : 2014 | Volume
| Issue : 2 | Page : 53-54
Clinical trials in India: Way forward
President, Clininvent Research Pvt Ltd, Mumbai, Maharashtra, India
|Date of Web Publication||1-Mar-2014|
A-302, Evesrest Chambers, Andheri-Kurla Road, Andheri (E) Mumbai - 400 059
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bhatt A. Clinical trials in India: Way forward. Perspect Clin Res 2014;5:53-4
"Your attitude, not your aptitude, will determine your altitude". Zig Ziglar
Since Jan 2013, the Indian regulatory authorities have announced a spate of laws and guidelines,  which will have a huge impact on the clinical trial sector in India.
| Reduced Speed of Clinical Trial Completion|| |
The speed of clinical trial (CT) completion depends on (1) time for regulatory approval and (2) recruitment of clinical trial patients.
The regulatory approval process is slow because of new requirements for submission and review of the CT.
The submission requires (a) the sponsor's undertaking of providing medical treatment and compensation in case of clinical trial related injury/death (b) the sponsor's commitment that they will market the drug in India after the trial is completed (c) submission of regulatory documents for New Drug Advisory Committee (NDAC) (d) changes in the informed consent form (ICF) to include compensation related clauses and (e) changes in the investigator undertaking to include safety reporting and compensation related clauses and (f) submission of the investigator's list containing 50% government sites.
The review of CT application is done by the Central Drugs Standard Control Organizations (CDSCO), New Drug Advisory Committees (NDAC), Technical Committee and Apex Committee.
Due to these changes, the regulatory approval takes around 9 months.
Recruitment of patients
The recruitment of patients depends on the availability of investigator sites and willingness of the patients.
The number of investigator sites has reduced as only registered institutional ethics committees (EC) can approve the clinical trial protocols. In addition, as the regulatory requirements are challenging and stringent, it is becoming increasingly difficult to convince the investigators to conduct the clinical trials.
The compensation clauses in ICF-compensation in case of death/injury, details of income, details of nominee-etc., may create anxiety and fear amongst the potential patients about the risk of participation in clinical trial. Further, the patients may be unwilling to undergo audio-visual (AV) recording of the consent process.
The investigator will need to devote special time for AV recording of the consent process. The investigator site has to report the analyzed serious adverse events (SAE) in timely manner-24 hrs and 10 calendar days - to regulators, expert committee, EC, head of institute and the sponsor. S/he has to be responsible for coordinating with the EC and sponsor the process of medical management and compensation. The investigator also needs to ensure that the site has adequate infrastructure, equipment, well-trained team and ready documentation to face regulatory inspection. Hence, there will be a tremendous increase in site burden-time and effort-in recruiting and managing clinical trial patients.
| Increase in Cost|| |
The site cost per patient will increase, as the investigator has to spend more time per recruited patient. The investigator has to devote time and effort to become aware of new regulatory compliance processes, to supervise and train staff in regulatory compliance and inspection readiness. She/he also has to be available for frequent and long monitoring and audit visits from the sponsor team.
The EC has to oversee the trial, and to review and comment on causality and compensation for SAE, document the EC discussions and decisions diligently and maintain records and be ready for regulatory inspections. This will mean an increase in the number and duration of EC meetings, and additional work for the EC members and support staff. This could result in increase in EC fees.
For the sponsor, in addition to the above, the cost of medical management, compensation for clinical trial related SAE, and exhaustive monitoring and audit will have a big impact on the trial budget.
However, the major question is: will these speed and cost changes improve the quality of clinical trial conduct?
| Ensuring Quality and Compliance|| |
The regulatory inspections conducted to check good clinical practice (GCP) compliance have highlighted areas of deficiencies in quality. Of the US Food and Drug Administration (FDA) inspections at 43 Indian sites, the finding was voluntary action indicated for 18 (42%) sites.  The inspection findings have been: (a) failure to follow investigational plan (b) inadequate and inaccurate records (c) failure to obtain and/or document subject consent (d) failure to notify Institutional Review Boards (IRB) of changes, failure to submit progress reports and (e) inadequate drug accountability.
The CDSCO's for-cause inspections have revealed compliance deficiencies in ethics approval, consent, and safety reporting. 
These regulatory inspection findings suggest that there are deficiencies in compliance to regulatory requirements for (1) human protection and (2) data integrity.
The challenge of meeting regulatory expectations of compliance and ensuring quality would require a change in mindset of all the stakeholders.
Post 2013, the EC's role has become crucial in ensuring rights, safety and well being of the clinical trial participants. The EC should devote time and efforts in re-learning ethical issues - human protection, independence in decision making, handling conflict of interest, reviewing safety reports and compensation, - and effective oversight of clinical trial conduct during the trial conduct.
The investigator, his/her staff and the sponsor's project team must be trained in (1) new regulations, (2) impact on the trial conduct, (3) the need for documentation and (4) regulatory compliance and inspections. During the clinical trial project training, the focus should be on  (1) specific study expectations (2) procedures unique to the product or the study (3) regulatory requirements (4) human protection concerns and (5) critical importance of the informed consent process.
It is essential for the investigator to understand and balance the need for quality and recruitment speed and aim for uniform quality standards for all clinical trials - investigator initiated, academic, local industry, global. This would require harmonization between research and practice and make documentation into effective vital practice for clinical trial conduct.
The sponsor has to invest a lot of time and effort in ensuring compliance to regulatory requirements and expectations. The monitors will have to conduct regular, frequent and long duration monitoring visits. It would also be essential to conduct regular audits at all the investigator sites during and after the completion of trial.
The sponsor has a vital role in ensuring compliance and should have a predetermined strategy for obtaining compliance from the investigator.  The monitoring reports should be reviewed expeditiously, and immediate actions should be taken to correct noncompliance. The sponsor should terminate participation of sites in the study, in case of persistent and serious non-compliance. The sponsor has to change from being accommodative to being assertive with the sites on compliance issues.
The new stringent and tough regulatory milieu requires an attitudinal shift, a paradigm shift from quantity to quality and from cost to compliance!
| References|| |
|1.||George B. Impact of recent regulations. Perspect Clin Res 2013;4:155-6. |
|2.||Ministry of Health and Family Welfare Lok Sabha StarredQuestion No185 answered on 24.08.2012. Available from: http://www.loksabha.nic.in/[Last accessed on 2013 Mar 21]. |
|3.||US FDA Clinical Investigator Inspection Search. Available from: http://www.accessdata.fda.gov/scripts/cder/CLIIL/index.cfm?fuseaction=Search.ShowAdvancedSearchResults [Last accessed on 2013 Nov 20]. |
|4.||Toth-Allen J Building quality into clinical trials-an FDA perspective Available from: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/UCM303954.pdf [Last accessed on 2013 Mar 8]. |