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LSW Conference Final Report
A meeting was organized by LSW to address the problems arising out of the Supreme Court order banning the conduct of clinical trials for new drug discovery programme of Pharma companies. This ban has resulted in uncertainty and major losses. Several foreign sponsors and CROs are affected. It is nearly two years that the ban came into effect and in spite of Govt. efforts the deadlock has not been resolved.
The meeting was held in Mumbai on May 27, 2014 at Hotel Orchid. It was well attended and had participation of the West Zone Deputy Director General of Drugs Dr.Bangarurajan, and experts like Dr.A K Agarwal, Dr.Y K Gupta as well as Dr.B M Gandhi. It was chaired by Dr. Surinder Kher, CEO of Ecron Acunova. (The list of participants is given at the end of this report.)
Right at the beginning Dr.Bangarurajan made it clear that he was very sympathetic to the problems faced by drug discovery companies and CROs due to the ban on clinical trials and he would strive to mediate with the DCGI and resolve the issues.
All the other participants made relevant remarks (Given at the end of this report). The meeting concluded on a positive note and a decision to forward the recommendations to Dr.Bangarurajan, who will take it forward to the DCGI. It was decided that a follow up meeting will be held in October/November 2014.
Gist of the conference proceedings:
Dr. B M Gandhi, Former Adviser, Government of India, Department of Biotechnology introduced the conference to the delegates in light of recent amendments to the schedule y of the Drugs and Cosmetics Act, report of the Ranjit Roy Chaudhry, mandatory audio-visual recording of the consent, serious adverse reactions and compensation and registration of ethics committees linked to the topics of the agenda.
Dr. K. Bangarurajan, Deputy Drug Controller (India) gave the inaugural address highlighting the “Regulations-Past, Present & future Scenario” highlighting the implications of the recent amendments in schedule Y, monitoring the clinical trials, NDACs, Ethics Committee registration and related issues.
Dr. Rao Vadlamudi , President, Indian Pharmaceuticals Association in his keynote address highlighted the challenges to bring new drugs to global market in present scenario of clinical research in India and advocated for GCPs in clinical research, enough number of sites, adequate regulatory support, sufficient resources and timely clearances by the regulatory bodies, responsive media for educating public and politicians and political will.
There was an active participation by the representatives of the industry drawn from different areas sharing their view point during session on “My Perspective on Clinical Trials sector in India-Where are we? Where are we going? Where we should be going?” Significant contributions were made by Jeroze Dalal (Glaxo SmithKline), Apurva Shah (Veeda Clinical Research, CRO), Dr. Prabhash Kumar, Head of Oncology, Tata Memorial Hosp. representing Investigators, Dr. Gururaj Rao, MD International Stem Cell Services Ltd on stem cells trials, Viveka Roy Choudhury, Editor, Express Pharma from the media’s perspective and Shradha Tawade, GM, Wockhardt (wife of patient who underwent clinical trial).
Elaborated session on “Compensation and Related Issues, Liabilities of Stakeholders and Mitigation” generated good interest and attraction.
Dr. Y. K. Gupta, Professor and Head, Department of Pharmacology, AIIMS discussed detailed information on recent amendments and post-scenario implications on compensation and related issues like basis of calculation of compensation and factors which entitles quantum of compensation. He informed that a Committee is already compiling the suggestions and recommendations in this regard and further suggestions, if any received, would also be considered.
Dr. A. K. Agarwal, Chairman, Compensation Committee, Government of India also informed that suggestions are open for debate and change. He further observed that about 50-60 cases of death are being reported in clinical trials besides subjects reporting permanent or partial damage/disability.
Dr. Milind Antani highlighted the importance of contract with the Project Investigator, Institute and Sponsors; role of CROs and Insurance Package for trial related injuries. Mitigation strategy should deal with liability and project Investigators should also get indemnified under the Professional Negligence Policy.
Other speakers included Dr. Suganthi Iyer of Hinduja Hospital, Jeroze Dalal from GSK, Dr. Venu Madhav, COO, Veeda Clinical Research and Dr. Prabhash Kumar as Panelists.
Presentations were made by industry professionals comprising Yasmin Shenoy , Sr. Director, Regulatory, Sanofi on “Beneficiary of Clinical Trial”; Dr. Rashmi Hegde, Director-Medical, Abbott “Liabilities of Stakeholders”; Deepak Gupta, Asst. Vice President, HDFC ERGO “on New areas of Clinical Trials That Can Be Covered by Insurance “Dr Viraj Suvarna, Medical Director, Boehringer Ingelheim India” Impact on Sponsor Company”; Milind Antani “Contracts” and Prabhash Kumar “Practical Issues and Concerns” These presentations were followed by in-depth discussions
The highlight of the conference was the presence of Dr. K Bangarurajan, Deputy Drug Controller of India, West Zone representing DCGI during the entire course of discussions at the conference and actively interacting with the participants. He addressed to all their queries on implications of the new guidance media perceptions. In his closing remarks, he assured the participants that he would carry forward all the discussion points and the suggestions made at the conference to the notice of CDSCO, DCGI and the Health Ministry.
Industry views for submission to the government:
- Expedite resolution of current PIL by enabling ISCR (CLG, Alishan Naqvi), IPA (Abhishek Manu Singhvi), who have filed an impleadment motion against the PIL, to speak. Or appoint an amicus curiae. This case has been dragging for 2 years now. The government has put in place multiple measures to protect patient safety. It’s time to let CTAs be approved so that patients in India can at least have a chance of hoping for a better life.The gazette notification on compensation is being amended but also needs to be reasonable in the case of outcome or event driven trials where the endpoint is a major CV adverse event. In such trials one wishes to evaluate whether the new drug is able to reduce morbidity and mortality better than standard of care. These are higher risk patients, some of whom will develop these SAEs/endpoints, but if sponsors have to compensate for such events in both arms they will never do such trials in India. Also, if the sponsor’s adjudication of relatedness is not aligned with that of investigator and/or EC there should be an option of going to an arbitrator or the Expert Committee should allow the sponsor to present its case to the Expert Committee.One needs to be able to differentiate between companies who follow strict standardized operating procedures when they conduct CTs all over the world. And companies who flout the law of the land. The former companies’ CTs are inspected by US FDA and EMEA and have passed so many such inspections, attesting to the data credibility and patient safety standards. Some of these companies have been doing global CTs in India for 20 years now and have always adhered to the highest standards of patent safety. Treatment of related AEs has always been paid for by the sponsor.One needs to understand the value to India of global CTs being conducted in India. Patients have benefited. Some have had a prolonged lease of life and get the drug free of cost for life (e.g., in cancer trials). Hospitals get state of the art equipment which they can use post-trial as well, e.g., 6 DEXA machines were donated to the institutes post a trial on a SERM for osteoporosis. Indian patients get access to the cutting edge research early and free of cost and even when the drug is eventually marketed in India it is at a lower price than elsewhere in the world.Operational hurdles need to be looked at rationally. For example, AV recording of the informed consent process should not deny a patient his right to participate if he does not want to be AV recorded. It could be risk-based AV recording, customized to only some patients and some trials which may need this kind of stringency.The CDA bill, if passed in its current state, may dissuade investigators from doing CTs, as the penal provisions may be too sweeping. Be balanced and fair, that’s all we are asking. The Ranjit Roy Chaudhry seems to be balanced. Let’s implement and streamline CT conduct across the country. Industry has always offered to facilitate training of CDSCO on site inspections, etc. Let’s clear the AIR (Academia, Industry, Regulator) by having more face to face interactions, e.g., NDAC is a good example of AIR.In short, we understand why this is happening, although we have always adhered to the highest global standards. We hope that these new regulations will weed out fly by night operators in CR and make India a uniformly clean place to do CTs on par with the best in the world, if not better.
- While there are several new regulations and enforcements that are a huge step in the right direction, there are a couple of areas where the intervention and advice of the DCGI office to the Ministry of Health and Welfare will result in a very beneficial position for the Indian patients.
- Retract the video consenting guidelines since this impinges on patient confidentiality
- Revoke patient compensation clause for cases of placebo related ADRs or absence of therapeutic effect
- Put in place and enforce stringent timelines for the approval process of New Drugs and CTs for New Drugs
- We need to have a mechanism in place for quick approvals for global trials, clarification on some of the clauses where compensation payments are applicable; clarity in formula used for quantum of compensation and accreditation of study investigators. All of these will not only enhance the quality of clinical data generated but will instill a sense of confidence to sponsors conducting future work in India.
- Insurance cover for Clinical Trials to be initiated.
- Special cover (insurance) for Investigators needed.
- Compensation issues to be made clearer. Compensation granted under labor laws and consumer protection act to be considered while considering the quantum of compensation in clinical trials.
- Clinical research is an important step for the advancement of science and benefit of mankind. It must be supported with appropriate regulations and have the right checks and balances.
- The compensation regulation has progressed considerably to iron out key concerns of all stakeholders
- Some concerns remain to be addressed : compensation to be paid by sponsor in case of scientific misconduct / negligence by investigator
- Clinical trial permissions should be expedited
- ISCR Suggestion
- Request CDSCO for a balanced approach for site selection
- Site with relevant experience, infrastructure and resources to meet the objectives of compliance to protocol, GCP and to ensure safety and well being of the trial participants
Clinical trial requirements
- First in class drugs
- Clinical proof of concept is critical
- Phase 3 Efficacy trials important
- Best in class drugs
- Phase 3 superiority trial is critical
- Biomarkers and clinical trial outcomes evaluations
- Bioequivalence studies critical
Clinical research, India-specific requirements
- Clinical research environment with GCPs
- Enough sites with good research background
- Adequate regulations to support clinical research
- Strong regulatory body with sufficient resources to make sound data–driven decisions to accord approvals
- Responsible media educating public and politicians and a political will!!
People actively involved in the trials should be important stakeholder for the policy formulation for the clinical trials
- To include clinical trial as a subject in MBBS curriculum.
- To include clinical trial as a subject in nurses curriculum
- To include clinical trial as a subject in administration curriculum
- Patient should be considered as a stakeholder in clinical research
- They should be considered as part of clinical trial development
- There are many advocacy group in western world, we should also encourage it in India
- Clinical trials should be considered a priority in the colleges
- Infrastructure needs to created for smooth conduct of clinical trials in medical colleges
- Trial for marketing and academic studies –This needs to be differentiated
- Regulation for new drug development and marketing should not apply to the comparative study of drugs available in the market which is freely available in the market
- There is no funding agency available for drugs in clinical trial in India
- There should be funding agency eg – DBT, DST which needs to fund clinical trials in India
- Clinical medicine and laboratory medicine works separately in India
- There should be incentives to ensure that clinical and laboratory medicine interact for clinical trials
Looking at the current scenario of Clinical Trial in India, it is high time that the government increases its participation. The ways to do would be:
- Drug Discovery sponsor companies → DGCI→IND to Govt. set-up CROs.
- Trials in government multi-specialty hospitals.
This will remove the problems involved in the CROs which have to make reasonable profit and have to carry out trials even where it is unwarranted.