Regulatory Aspects of Clinical Trials

 

Introduction:

            According to World Health Organisation,

“Clinical trials are a type of research that studies new tests and treatments and evaluates their effects on human health outcomes. People volunteer to take part in clinical trials to test medical interventions including drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioural treatments and preventive care.” ⁽¹⁾

Until late nineteenth century there was a belief that the accomplishment of therapeutics cannot be known and communicated. The discovery of penicillin and sulfanilamide put an end to this and the belief about the science, medicine and drugs improved thereafter. Clinical trials were the mainstay in the development of effective drugs for various diseases like cardiovascular disease, cancer and vaccines successfully in twentieth century. Twenty-first century is leading to precision medicine and drug discovery for rare diseases. ⁽²⁾

            Clinical trials are meticulously planned, well-designed, and methodical; protocol based experimental studies that are carefully considered to assess the safety and efficacy of a drug or device. Regulatory bodies play a key role in ensuring and enhancing the accuracy, completeness and comprehensiveness of a clinical trial. ⁽³⁾

Purpose of Regulatory Bodies:

            As clinical trials involve human participants it is imperative to adhere to ethical practices proposed by the regulatory bodies. The regulatory health authorities are different and exist as independent bodies in different countries.

 

 

Though the principal objective of them is to define specific regulations following the Good Clinical Practice (GCP) guidelines to

·       Protect the participant’s right, safety and wellbeing

·       Follow the principle of beneficence

·       Voluntariness of the subject

·       Protect subject’s privacy and confidentiality

·       Transparency about the trial to the subject

·       Accountability and

·       Risk minimization.

Table 1 : History of events of unethical practices and evolution of ethical principles ^(3,4)

Event	Principle
1937 : Elixir Sulfanilamide tragedy	1938 : Federal Food Drug and Cosmetic Act
1945-1947 : Nazi experiment	1947 : Nuremberg Code 1948 : Declaration of Geneva (World Medical Association)
1960 : Thalidomide tragedy	1964 : Declaration of Helsinki
1972 : Tuskegee Syphilis Study	1979 : Belmont Report

Regulatory Attributes of Clinical Trials:

            Clinical trials are carried out in different phases (I-IV) that abide by the specific guidelines and necessary regulatory documents that are submitted to the regulatory bodies throughout the clinical trial. Comprehensive and credible information of the clinical trial should be submitted to the appropriate regulatory authorities to enable data driven decision-making. ⁽³⁾

            Examples of some of the essential documents to protect during the process of clinical trial that supports the regulatory submissions are ^(3,5)

·       Investigator’s Brochure

·       Study Protocol

·       Ethical Clearance

·       Informed Consent Form

·       Clinical Report Form

·       Adverse Reactions/Serious Adverse Reactions Reports

The important regulatory activity in a clinical trial is to update the amendments and safety reports to the regulatory authority (RA) and the ethical committee. ⁽⁶⁾ Some of the significant updates that need to be reported are

·       The protocol amendments of an existing Investigational New Drug (IND) application like the scope of the investigation, protocol changes to minimize the risk or to ensure the safety of the subjects.

·     Recruitment of new investigator to conduct a previously submitted trial should be reported within 30 calendar days.

·     Potential risks of the investigational product should be notified.

·     Each safety report should be reported by the sponsor to RA within 15 calendar days and serious adverse events (SAE) within 7 calendar days.

·     Annual safety reports should be submitted according to the guidelines of the RA.

    

Conclusion:

            The process of clinical trial is designed such that each and every phase of it involves concurrent regulatory activities. All the regulatory activities in the clinical trial mark the credibility and authenticity of the trial and serves as a milestone in the clinical trial progress. These regulatory activities assist in monitoring and evaluating the safety and efficacy of a drug or an investigational product during the progress of the clinical trial and also to implement risk minimization plans and regulatory guidelines for the advantage of the public.

References:

1.         Clinical trials [Internet]. [cited 2023 Oct 6]. Available from: https://www.who.int/health-topics/clinical-trials

2.         Piantadosi S. Clinical Trials: A Methodologic Perspective. John Wiley & Sons; 2017. 931 p.

3.         Kandi V, Vadakedath S, Addanki PS, Godishala V, Pinnelli VB. Clinical Trials: The Role of Regulatory Agencies, Pharmacovigilance Laws, Guidelines, Risk Management, Patenting, and Publicizing Results. Borneo J Pharm. 2023 Feb 28;6(1):93–109.

4.         Kim JH, Scialli AR. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol Sci Off J Soc Toxicol. 2011 Jul;122(1):1–6.

5.         Gogtay NJ, Ravi R, Thatte UM. Regulatory requirements for clinical trials in India: What academicians need to know. Indian J Anaesth. 2017 Mar;61(3):192–9.

6.         Chiodin D, Cox EM, Edmund AV, Kratz E, Lockwood SH. Regulatory Affairs 101: Introduction to Investigational New Drug Applications and Clinical Trial Applications. Clin Transl Sci. 2019;12(4):334–42.

 

Student Name: Dr.Sakthiyavathi K

Student ID: CLS_181/092023

Qualification: BDS

e-Mail ID: drsakthi.official@gmail.com