Clinical Trials in India

India is an emerging hub for clinical trials.¹  

India is one of the top five choices for clinical trial.¹

Total number of trials registered in India in CTRI: 47239^*2

^{Clinical trials hold significant potential in:}

• Benefitting patients
• Improving therapeutic regimens
• Ensuring advancement in medical practice²

^{*As on 11th Nov. 2022.}

Type of clinical trials³

• Cohort study:
  A study of two groups one with pre-existing condition and one without.
• Randomized controlled trial:
  Trial randomly assigning patients to 2 or more groups in a controlled way.
• Case-controlled study:
  Patients with outcomes are studied to ascertain their experience.
• Cross-sectional study:
  Observation of a defined population at a specific time.

Process of a clinical trial⁴

1. Trial funding:

Costs involved in a clinical trial are huge and securing a funding is of utmost importance before the trial. Careful planning and budget allocations are needed to secure the finding. Before choosing a funding agency, look for:

Some of the Indian funding bodies include:

• Indian Council of Medical Research (ICMR)
• Department of Biotechnology (DBT)
• Ministry of Science and Technology
• Indo-US Vaccine Action Programme (VAP)
• Biotechnology Industry Research Assistance Council (BIRAC)
• Council of Scientific and Industrial Research (CSIR)
• Department of Health Research

2. Protocol development⁴

A document that defines the objectives, hypothesis, rationale, study design and methodology is known as protocol. A well-designed study relies on a robust and standard protocol.

The New Drugs and Clinical Trials Rules, 2019 shares the essentials of a protocol document.

Here are few sites helpful for protocol writing:

• SPIRIT statement
• NIH Protocol writing guideline (https://e-protocol.od.nih.gov/#/home)
• Protocol template by NHS (https://e-protocol.od.nih.gov/#/home)
   

3. Essential documents⁵

Essential documents are the documents required for conducting a clinical trial. They individually and collectively ensure the quality and completeness of a trial.

For a detailed list of the documents, please refer https://ethics.ncdirindia.org/ClinicalToolkit.aspx

Appendix V of Good Clinical Practices and the Indian ICH-GCP guidelines⁶ provide the list of essential documents.

4. Approvals

Next step of the process is getting approval for conducting the trial.^7,8

All trials must be registered on the CTRI website. It is not mandatory for observational studies to register on the CTRI website, but if submitted they are useful guides to others who might want to conduct similar studies.⁸ 

IEC approval is necessary for all clinical trials.⁹

Academicians who carry out trials with 'new drugs' no longer need approval from the DCGI; only IEC approval is required. This is provided that these studies are not intended for generating data to make a regulatory submission.⁹

^{Additionally, clinical trials can be registered on CTRI website:
http://ctri.nic.in/Clinicaltrials/login.php.}

5. Trial conduct

Once the approvals are in place, the trial is conducted on site. The most important aspects of clinical trial conduct are data collection and data management.

Clinical data management leads to the generation of high-quality, reliable and statistically sound data required for clinical trials.

Hierarchy of evidence¹⁰

The hierarchy of evidence and the role of the individual participant data (IPD)
meta-analysis in knowledge creation is presented.

How to collect clinical data?¹¹

Data management involves, generation of:

• High quality,
• Reliable, and
• Statistically sound data

Proper data collection is important as it helps in reducing time from drug development to publishing.

Examples of some useful data collection tools^11,12

• EpiInfo
• Oracle Clinical
• Clintrial
• Macro
• Rave
• eClinical Suite
• Nvivo
• Mini Tab

Post this, statistically tabulating them to get the results is done through biostatistics. Several websites help in this, for example, SPSS, OpenEpi, Stata, SAS and MetLab.¹¹

Key questions to ask while assessing clinical data^13,14

• Is the research question expressed clearly?
• Is the research question justified and related to the existing knowledge base
  (empirical research, theory, policy)?
• Is the method used to get ethical and/or research/institutional governance explained and cited?
• Method: Does the treatment have a clinically relevant benefit that outweighs the harms? (Statistical significance)
• Is another treatment better? (Compare benefit vs harm profiles)
• Is this treatment feasible in my setting? (Interventions analysis)
• Is there publication bias? (Already existing trial registries and conflict of interest)

Publishing the results¹⁵

Publishing the results are imperative to the trial, no matter positive or negative. It adds to:

Things to look out for while finalizing a journal:

• Check for indexing with PubMed, Embase, Index Copernicus, etc.
• Check for cost (if charged high)
• Publishers of the journal are week-known
• Acceptability rate

BIRAC: Biotechnology Industry Research Assistance Council; CDSCO: Central Drugs Standard Control Organisation; CISR: Council of Scientific and Industrial Research; COVID: Coronavirus disease; CTRI: Clinical Trials Registry-India; DBT: Department of Biotechnology; DCGI: Drugs Controller General of India; DEC: Departmental ethics committee; ICH-GCP: International Conference on Harmonisation – Good Clinical Practice; ICMR: Indian Council of Medical Research; IEC: Institutional ethics committee; Indo-US VAP: Indo-US Vaccine Action Programme