Phases of Clinical Trials

09/21/2019

Globally, various regulatory bodies and authorities provide guidelines regarding the design and conduct of clinical studies. Typically, any clinical study involves 5 different phases. Phase 0 involving very limited human exposure to the drug, with no therapeutic or diagnostic goals, is followed by Phase 1, wherein the maximum tolerated a dose of a drug and its safety are assessed in a small group of healthy individuals. Phase 2 determines the drug's efficacy inpatient population; while in Phase 3, the drug is tested in a bigger patient group across different geographical locations and cultures. Finally, Phase 4 or a 'post-marketing study' is conducted post-drug approval by the Food and Drug Authority (FDA) and/or other regulatory authorities.

Improvement in Indian Regulatory Environment over the Years:

There have been constant updates to policy and guidelines governing the conduct of clinical research in India in the past few years. The fundamental objective of these updates was to give topmost priority to patient safety in an overall difficult regulatory environment. However, Indian regulations have seen positive development in the recent past to favorably support clinical research, while simultaneously focusing on patient safety. These regulatory changes will facilitate the entry of newer innovative medicines to Indian patients at the earliest.

Today, a comprehensive policy and guidelines for all aspects related to approval of new drugs and clinical trials are in place as a result of a setback received by the industry in 2012-13.

Some Major Improvements in Indian Regulatory Environment can be listed as:

The three-tier review process for clinical trial applications (By SEC Meeting, Technical Committee, and Apex Committee)
Compensation and free medical management (In case of trial-related injury or death)
Mandatory Ethics Committee registration
Audio-Video recording of Informed Consent process
Tougher requirements for site selection
Regulatory inspections

In addition, other regulatory updates suggest that academicians conducting trials with 'new drugs' no longer need approval from the DCGI for the conduct of the trial and IEC approval would suffice. Also, customs authorities at the port of entry/exit shall permit the export of biological samples without prior approvals from any government agency, provided the concerned firm submits an undertaking confirming adherence to rules for safe transfer, and disposal of biological samples.

The rising number of clinical trials post new regulations in 2014

(Ref: Bhave A, Menon S. Regulatory environment for clinical Research: Recent past and expected future. Prospect Cline Res 2017; 8:11-6)

Approval for Conduct of Clinical Trials-Indian Scenario:

The CDSCO is the central authority overseeing the overall drug development and clinical trials, as mandated under the Drugs and Cosmetics Act. Drugs and Cosmetics Rules (Rules 122A, 122B, and 122D, 122 DA, 122DAA, 122E) along with Appendix I, IA and VI of Schedule Y, describe the information/data required for approval of clinical trial and/or to import or manufacture the new drug for marketing in the country. All clinical trials for a new drug, whether for clinical investigation or any clinical experiment by any institution, should only be conducted under, and in accordance with, the permission, in writing, of the Licensing Authority defined in clause (b) of Rule 21. Phase III trials are required to be conducted in India, with data of at least 500 patients distributed over 10-15 centers, before permission to market the drug in India is granted.

Required Information While Applying for Permission to Conduct Phase II and Phase II Studies:

A summary of all the non-clinical safety data already submitted while obtaining the permissions for Phase I trial, with appropriate references.
In case of an application for directly starting a Phase II trial - complete details of the nonclinical safety data needed for obtaining the permission for Phase I trial, as per the list provided above must be submitted.
Repeat-dose systemic toxicity studies of appropriate duration to support the duration of proposed human exposure
In-vivo genotoxicity tests.
Segment II reproductive/developmental toxicity study (if female patients of childbearing age are going to be involved)
Carcinogenicity studies (when there is a cause for concern or when the drug is to be used for more than 6 months) especially in the Phase III trials.

The Indian clinical research industry went through a difficult phase in 2013 and 2014. However, late 2014 and 2015 saw the Indian regulators taking steps to diminish the challenges posed by regulatory uncertainty; and concerns of stakeholders were addressed through amendments in regulations, new orders, and further guidance on existing ones. Compared to the last few years, where the clinical operations and conduct of clinical trials had become stalled, more and more pharma organizations are approaching DCGI with the applications for conducting clinical trials in India. CDSCO, in 2015, had also planned to introduce a system of formal Pre-submission Meeting of applicants with CDSCO officers and subject experts to discuss the regulatory pathway of their respective application. Also, a recently launched tool- SUGAM by CDSCO-will facilitate online applications as part of efforts to increase accountability, transparency, and efficiency for faster processing of applications. Furthermore, India, owing to its status as the second most populated countries in the world, has 1/5th of the global disease burden with large unmet medical needs for its patients. Therefore, there is a huge demand for developing new drugs. Effective and ethical clinical trials are the only way to introduce safe and efficacious molecules in the market. Indian regulatory bodies will hopefully continue to play a positive role in promoting local research and innovation. The good progress made by the Indian clinical research industry should maintain its momentum, as millions of patients are waiting in the hope of better and more effective treatment.

Moreover, Conducting Clinical Trials in India Has Some Added Advantages as Follows:

The Indian environment is again becoming conducive to clinical trials as a result of refined regulations and reduced approval times.
Conducting trials in an emerging market like India, where expenses are lesser and the patient pool is bigger, can significantly benefit sponsor pharmaceutical companies, while also helping the local healthcare system and the economy of the developing country.
With not only the huge population but also ever-improving socioeconomic status; India is one of the rapidly growing destinations for both the conduct of the clinical studies as well as the marketing of new drugs.
With GCP and investigators at par with the global standards, supported by a large patient base, Indian clinical trials could be the solution that the industry is seeking for high-quality data, expeditious study enrolments, and low cost.

Veeda Clinical Research is a rapidly growing CRO in India, where we strive to keep up with the current regulatory updates and provide our customers with comprehensive services, such as Phase II-III clinical trials, feasibility studies, end-to-end regulatory submissions, comprehensive project management, data management and statistics solutions among others.