India: Quality for Clinical Trials

India clinical trials quality assurance

Quality Systems in India

Are Quality Systems in place in India, where the clinical trials industry is exploding?Do clinical trials professionals have the knowledge, skills and experience to run clinical trials where the rights, safety, & welfare of human subjects is protected and where data are reliable for submission to FDA and EMA> In this Guest Commentary QA professional Anusha Reddy demystifies the GCP process in India outlining her approach to quality in clinical trials.

This marks the first edition of GxP Perspectives as a monthly blog. It has been too much work for one person to keep up with a weekly schedule. I will be using the GxP Perspectives Linkedin Group to keep on top of current developments with FDA, as well as discussions by group members. Also, youcan subscribe to the blog on the button to your right on the sidebar.

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Improvising Quality in Clinical Trials

By Anusha Reddy

Over the last decade Clinical Trials in India have increased very rapidly in number. India has made a name for itself in the international pharmaceutical field as an ideal destination for worldwide companies to conduct clinical trials which is a test for both the government and the private sector to create a balance between ethics and trade The rise in the business brought sharp focus on the need to manage quality while conducting clinical trials.A need was, however, felt to develop our own Indian Guidelines to ensure uniform quality of clinical research throughout the country and to generate data for registration for new drugs before use in the Indian population. An Expert Committee set up by Central Drugs Standard Control Organisation (CDSCO) in consultation with clinical expert has formulated GCP guideline for generation of clinical data on drugs.

The Drug Controller General of India (DCGI) has introduced several guidelines and regulations, in an effort to maintain and ensure credibility, integrity, safety, well being and quality of clinical trials, some which includes guidelines on approval of clinical trials, CTD, Clinical trial Inspection, registration of clinical trials, CROs, and Ethics Committee’s. It constituted NDAC to review applications of new drugs and clinical trials, introduced prescreening of applications in order to expedite and streamline the process of application by ensuring completeness and has recently made compensation mandatory for injury or deaths during trials and which would increase the number of volunteers and patients going for a trial in India, according to experts.

quality clinical trials in India

"Each Stage of Data Handling"

Quality in clinical trials should be applied to “each stage of data handling” to ensure that all data are reliable and have been processed correctly. Clinical trials are carried out to allow safety and efficacy data to be collected to provide information for industry and regulators to make decisions about the safety and efficacy of the interventions. Activities like monitoring and auditing are performed in order to ensure that the quality exists and the study is conducted in accordance with the SOPs, Protocol, GCP and applicable regulatory requirements. Pharma and Biotech firms are looking for several different strategies in clinical trials to ensure the highest quality of data. This article tries to discuss on describing and executing the quality in clinical trials.

A good quality clinical trial should, address an important question, have the potential to make an actual difference to patients, use the finest available research techniques, generate significant data, be scientifically and ethically sound. Recognition of GCP at the sponsor, CRO and the investigator site will improve the quality of clinical trials and finally leads to the acceptance of clinical trials.

clinical trials quality India

"Ability to Satisfy Stated or Implied Needs."

As per ISO (International Organization for Standardization) quality is defined as the features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs. In clinical trials, poor quality has much more serious outcomes than discontented customers. Failure to ensure quality in clinical trials can result in undue harm to research participants, invalid data, and consequently, wrong conclusions about the safety and efficacy of the drug being tested. Additionally poor quality is a call for a regulatory inspection.

Determined efforts to improve quality in clinical trials have increased noticeably over the past decade. Recently the Department of Medical Education has imposed a temporary ban on clinical drug trials and research projects in all government and private medical colleges and hospitals in the Karnataka State, India; however, later it was assured that no such measures are being undertaken. The reason behind such decision was especially lack of guidelines to regulate drug trials. An expert committee was set up to study and frame guidelines to regulate and re-organise clinical drug trials, which is a step towards a quality clinical trials.

quality India clinical trials

The Consequences of Poor Quality

There are several reasons for poor quality in clinical trials and preventing them all is not an easy task. The objective should be to limit their number and their effect on the trial outcomes. This can be achieved by taking steps at the initial stage in protocol development and at the trial set up phase to obtain a high quality data in clinical trials; however, this alone does not result in high quality. Furthermore, planning should be accompanied by adequate oversight through proper routine monitoring and auditing of the trials with necessary corrective and preventive actions (CAPA) in place.

Measures should be taken to promote quality improvement in clinical trials by following standard operating procedures and implementing good documentation practices while performing study activities like drug accountability, Informed consent process, Safety reports, protocol deviations/violations and other protocol related activities which will provide reliable results and error free data when submitted to regulatory agencies for approvals.

A quality system proposition to good clinical practice conformance will establish quality in clinical trials by identification and setup of standards, applying them by those involved in the conduct of clinical trial, tracking the areas that are non-complaint with the standard procedures or applicable regulatory requirements, take actions to prevent the recurrence in future in the identified areas.

quality in India

Developing Metrics

Developing and using metrics that are meaningful within an organization facilitate in measuring the quality in clinical trials. For example, preparing a protocol from the stage of drafting to finalizing, here with increase in amendments the time increases and quality is reduced (but number of amendments is often not the reflection of protocol quality). Other example for measuring the quality includes the number of data clarifications forms (DCFs) raised per case report form (CRF); increase in the number of data queries indicates the poor data quality. Based on these metrics one can measure the quality and can improve those areas.

In Conclusion, systems with procedures or measures that assure the quality of every aspect of the clinical trial should be implemented. Quality should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly. This extent of transparency and accountability of clinical trial processes ensures ongoing quality control and quality assurance, but in addition, makes it easy to assertively address inquiries from regulatory agencies.

Useful Links:

Indian GCP

Clinical Trial Registration

Prescreening Checklist


Training Opportunity:

The 3rd Proactive GCP Compliance Conference taking place April 2-4 in Arlington, VA – GCP Conference Website. Leading GCP experts from Lilly, Pfizer, J&J, Novartis, Shire and many more address risk-based approaches to clinical quality that meet requirements and ensure patient safety. Special 15% discount off of the standard registration rate for GxP Perspectives readers. Register online at: GCP Conference and use discount code: P439GXP


DIA Regulatory Conference this April in India

In News From FDA:

FDA has issued the final guidance, “IRB Continuing Review after Clinical Investigation Approval.” GCP Guidance Documents may be found here: FDA GCP Website. The new guidance is on the right in the section “In The News.”

From: A Message from the Commissioner
Sent: Wednesday, February 29, 2012 04:14 PM
To: FDA-Wide
Subject: Announcement re Chief Counsel

Dear Colleagues,

I am thrilled to announce the permanent appointment of Elizabeth Dickinson as the Chief Counsel of the Food and Drug Administration, effective Monday, March 12, 2012.

As many of you know, Liz has had a long and distinguished history at the Agency; she joined the Office of the Chief Counsel in 1994. Over the years, Liz has served as legal counsel to the Center for Drug Evaluation and Research and the Office of the Commissioner on innovator and generic drug review issues, orphan drug development, and biosimilars; has implemented pediatric exclusivity and pediatric drug development programs; has worked closely with the Department of Justice on dozens of cases addressing Waxman-Hatch issues and preemption; and has coordinated the development of the Office of the Chief Counsel’s flexible workplace program.

A graduate of the University of Massachusetts and Northeastern University School of Law, Liz is highly regarded by both her internal colleagues and those across the food and drug bar. Over the years, Liz has received numerous awards for distinguished service, leadership and her outstanding legal skills.

Liz has been serving as Acting Chief Counsel since August 2011, and we have been grateful for her hard work and dedication each day that she has been on the job. It is terrific to know that she will be serving the Agency in this role permanently as we move forward. Please join me in congratulating Liz.

Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs

We have some excellent comments on this post. Please join the discussion and add your own thoughts

5 Responses to India: Quality for Clinical Trials

  1. Steve Steinbrueck says:

    I intend to write more later, but wanted to register my first impressions. I am a bit concerned that this review addresses the quality of data while nearly ignoring the research community’s ethical obligations, namely, the protection of the rights, safety and welfare of research subjects. I, and I believe many, have concerns that the rapid expansion of trials in regions that do not have an established infrastructure to safeguard these things (e.g., experienced investigators, ethics committees, etc.) and where access to medical care and complex cultural and language issues raise concerns regarding the vulnerability of research participants and real issues of ethically valid consent. Ethics first, data second–more later…

    • srinivas says:

      i too agree. The first concern in any trial is patient safety, followed by other things. Data quality etc are important in perspective of sponsor and may influence end result/CSR irrespective of patient safety concerns.

      The main issue is does the whole ecosystem in india is enough qualified, trained etc to conduct CTs keeping the sole objective in mind. This includes PIs, IECs, DSMBs etc inc DCGI, ICMR.

  2. Anusha Miriyala says:

    Hi Steve Steinbrueck,

    I understand your concern.

    I am a bit concerned that this review addresses the quality of data:

    Firstly the article above discusses not only about the growth of clinical trials in India but also about the growth in quality by introducing various systems that govern the clinical trials. It list the regulations and guidelines that the DCGI has put its efforts in re-framing and updating the clinical trial system for the betterment of clinical trials in terms of Quality, which i felt was not enough as there should be efforts need to be put by the clinical research professionals too, as the main obligations lies with them in generating the quality data in terms of safety and efficacy in the conduct of the trials.
    Following guidelines is not enough because they guide you by providing broader scope let’s take an example “monitoring report: the ICH GCP says that report should capture what the monitor has reviewed , the findings/facts, deviations, actions taken etc” but it does not list out what activities should they review (like site staff, study progress and recruitment, safety aspects, regulatory and ethical requirements, informed consent etc) and capture the findings which is important because based on that quality of the trial is decided. So what matters is how you bring quality following guidelines and regulations which is possible by implementing quality at each stage of clinical trial starting from designing of the study documents to generating clinical study reports. So I have focused on bringing quality in Clinical Trials.

    While nearly ignoring the research community’s ethical obligations, namely, the protection of the rights, safety and welfare of research subjects:

    Ethics: I have listed in the article the below rules intrduced by DCGI for safeguard of rights well-being and welfare of clinical trial subjects:
    Clinical Trial Resgitration : All the trials should be registered disclosing details of the 20 mandatory items of the WHO International Clinical Trials Registry Platform (ICTRP) dataset and a few additional items. This will help improve reliability of data generated, help clinicians interpret research, minimise duplication of trials, and prevent exposure of volunteers to potential risks.

    Registration of the Ethics committees . All ECs should be registered with ICMR (Indian Council of Medical Research) so that the DCGI (also called Licensing Authority) can have a direct control on the functioning ECs. Also Ethical approval should be obtained from Ethics Committee located in the same area where the clinical trial site is located, accountable to ensure that conducted trial is suitably monitored safety and well being of subjects and in compliance with Indian and international GCP guidelines.
    Compensation for the injury or death: Sponsors/CRO’s provide complete medical care to the participants in clinical trial.

    Do not have an established infrastructure:

    Infrastructure: India is one the major player in the clinical research arena for many well established reasons, which are not limited to availability of ethnically and genetically diverse treatment naïve patient population, but extend to the inherent availability of expertise in all therapeutic areas, a highly enabled IT infrastructure and increasingly more stringent intellectual property protection (TRIPS). Cost effective research is complemented by high quality study data generated in accordance with international standards. This is further enhanced by the fact that English is the spoken language. These are the reasons why India has become a hub for Clinical research and also o majority of trials are being outsourced to India.

    Hope the above clarifies your concerns..

  3. GxP Perspectives says:

    When I asked Anusha to write a post for the blog it was on the topic of quality. I have many Guest commentaries that do not address ethics issues that many people find helpful, for example on the Trial Master File. I also give people a maximum number of words to use. I publish COMMENTARY, not books. I think that having commentary, the writer’s own perspective, is important, particularly from writers outside the United States where I am located. I welcome a lively discussion and hope others will comment. But please remember the context and that context tells us a lot.

    Carl Anderson
    GxP Perspectives

  4. Prof. Arun Chougule says:

    Yes, Certainly quality of clinical trials is must to draw meaningful conclusions but more important is ethical obligations of the PI towards participant. Due to poor educational and social background of the participants, the informed consent become mare a piece of paper on which thumb impression/ signature is obtained. In many clinical trials its CRO and his team is doing all the job and PI is mare a facilitator to provide the subjects by virtue of his chair/post in the institute where clinical trial is going. No sufficient time given to explain the participants about the purpose of the study and benefits/risks of participating in the study. Competency of PI in the specialty/subject of clinical trails need to be loked into by IEC and not mare formalities of granting the permission. There is no mechanism or sufficient staff with IEC to supervise the clinical trails.

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