Clinical trial refers to any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy.
Since clinical research is a highly specialized job function requiring specific skill-sets to carry out various operations. To carry out these functions effectively, there is a need of training need at the level of individual stakeholder. The various stakeholders in clinical research include:
" Sponsor(s)
" Contract Research Organizations (CROs)
" Investigator(s)
" ERB/IRB/IEC/EC
" Regulatory Authorities
Specialized training requirements include training on clinical trial process, Standard Operating Procedures (SOPs), GCP and applicable regulatory guidelines. Requirements for individual stakeholder may vary based on his responsibility but some of the training elements remain common for all stakeholders.
Sponsors & Contract Research Organizations (CROs)
According to ICH GCP guidelines, Sponsor is an individual, company, institution, or organization, which takes responsibility for the initiation, management, and/or financing of a clinical trial. Contract Research Organization (CRO) refers to a person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions.
Since both sponsor and CRO assume major responsibilities their training levels impact the overall quality of a clinical trial. In addition to the basic educational qualification the essential clinical trial training elements for a sponsor & CRO representative include:
1. Drug Development & Clinical Trial Process: It includes detailed training on role of clinical trials in drug development, phases of clinical trials, trial design, methodology & bio-statistics etc.
2. Good Clinical Practice Guidelines (all that applicable)
- ICH-GCP Guidelines, 1997
- Ethical Guidelines for Biomedical Research on Human Subjects, 2000 (ICMR Code)
- Indian GCP Guidelines, 2001
3. Standard Operating Procedures (SOPs): It refers to a set of pre-established written procedures for the organization, conduct, documentation, data collection, verification and reporting of a clinical trial. These are required to ensure that the rights and integrity of the trial subjects are thoroughly protected and to establish the credibility of data in order to improve the ethical, scientific, and technical quality of trials.
SOPs provide the link between the guidelines and actual practice. Typical SOPs used by the sponsors and CROs includes topics such as:
- SOP on SOP
- Essential Trial Documents Development, Retention, Amendments & Disposition
" Protocol
" Informed Consent Document (ICD) & Privacy of Personal
Health Information
" Investigator's Brochure (IB)
" Clinical Report Form (CRF)
" Trial Master File & Site Files
- ERB/IRB/IEC/EC
- Project Management
- Budgeting
- Manufacturing, Packaging, Labeling, Coding & Accountability of Investigational Product
- Appointment & Management of Central Labs
- Investigator Selection/Evaluation
- Regulatory Submission
- Imports/Exports
- Investigator's Training
- Investigator's Site Initiation
- Pharmacovigilance & Safety Reporting
- Clinical Trial Monitoring
- Deviation, Violation & Non-compliance
- Financial Agreements
- Randomization, Blinding & Unbinding
- Data Management
- Audits, Quality Control & Quality Assurance
- Investigator's site Closure, Termination, Suspension
- Trial Closure, Termination, Suspension
- Clinical Study Report
- Storage & Archival
4. Therapeutic area & required computer training
5. Protocol, IB, ICD, CRF & other trial procedures
Investigators
According to ICH GCP guidelines, Investigator is a person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the Principal Investigator.
Since investigator is responsible for the trial conduct at a site he is responsible for safeguarding the patient's rights and well-being as well as ensuring the integrity of trial data. In addition to the required educational qualification (as specified by law) the essential clinical trial training elements for an investigator includes training on:
1. Drug Development & Clinical Trial Process: It includes an overview of drug development & clinical trial process.
2. Good Clinical Practice Guidelines (all that applicable)
3. Standard Operating Procedures of the hospital/institute (if any)
4. Protocol, ICD administration, CRF, IB, Trial files etc.
5. Investigation Product Storage & Accountability
6. Trial Procedures, Safety Reporting, Logistics Management and Inventory Planning.
ERB/IRB/IEC/EC
According to ICH GCP guidelines, IRB is an independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.
In addition to the required educational qualification the essential clinical trial training elements for IRB members includes training on:
1. Drug Development & Clinical Trial Process: It includes an overview of drug development & clinical trial process.
2. Good Clinical Practice Guidelines (all that applicable)
3. Standard Operating Procedures/Charter of the IRB
4. Essential Trial Documents, Trial Procedures & Safety Reporting
Regulatory Authorities
According to ICH-GCP guidelines, regulatory bodies refer to the bodies having the power to regulate. It includes the authorities that review submitted clinical data and those that conduct inspections. These bodies are sometimes referred to as competent authorities.
While ERB/IRB/IEC/EC is responsible for reviewing & approving/disapproving the trial protocols and procedures at individual hospital level, regulatory authorities are responsible for reviewing & approving/disapproving the trial protocols and procedures at country level. In addition to the required educational qualification the essential clinical trial training elements for Regulators includes training on:
1. Drug Development & Clinical Trial Process: It includes an overview of drug development & clinical trial process.
2. Good Clinical Practice Guidelines (all that applicable)
3. Drugs & Cosmetics Laws/Code of Federal Regulations
4. Essential Trial Documents, Therapeutic Area, Trial Procedures & Safety Reporting
It is recommended that all the stake-holders should be thoroughly trained on their required elements before allocating responsibilities. Failure to this can lead to inconsistency, deviations and non-compliance that can jeopardize the trial data/outcome.
Although sets of robust guidelines which governs the conduct of clinical trials are available, it is still looked upon as an area of humanitarian concern, at times. The situation is even worse in India when we see misconducts and illegal drug trials becoming media spotlight quite often. The underlying reason for it could be the lack of: technical know-how, clinical research training, regulatory inspections and unwillingness to comply with the guidelines.
At this point of time when India is being looked upon as a preferred destination for conducting global clinical trials, ethical conduct of these trials is essential to capitalize the opportunity that comes to our way. Imparting the required professional training to each stakeholder is mandatory for the development of clinical research industry in India.
(The author is director, Clinical Operations, Catalyst Clinical Services Pvt. Ltd,
Delhi)