Clinical research in India is at a standstill.The carry over of the contentious compensation clauses introduced in January, 2013 has not moved forward on draft amendment. There is no ‘provisionally final’ formula for compensation nor mandatory audio visual recording of informed consent. But there is a cap on number of trials by an investigator , limitation on distribution of sites in a trial, random and indiscriminate site inspections by relatively untrained staff and delays in regulatory approvals, according to the Indian Society of Clinical Research.

On April 24,2014, the Ministry of Health and Family Welfare issued the draft notification of with an amendment of 122 DAB for which comments were submitted, and we are expecting the same to be in 2015, Suneela Thatte, president, ISCR told Pharmabiz.

The first gazette notification was G.S.R. 53 (E) dated January 30, 2013, with insertion of Rule 122 DAB which specifies procedures to analyze the reports of serious adverse events (SAEs) occurring during clinical trials and payment of compensation in case of trial related injury or death as per defined timelines. The detailed process was explained with the addition of Appendix XII in Schedule Y. Then came in a second gazette notification of G.S.R. 63(E) dated February1, 2013 with insertion of Rule 122 DAC which specifies conditions under which application for conduct of clinical trials should be approved by licensing authority, which included a critical point that the sponsors along with their subsidiaries, agents,sub-contractors, and clinical trial sites should allow inspectors authorized by CDSCO to inspect their premises. This was followed by a third amendment which was related to mandatory registration of the Ethics Committees (EC) in the Drug and Cosmetic Act vide G.S.R. 72(E) dated February 08, 2013 with addition of Rule 122 DD.

“This 122DAB has been a contentious issue . This came about in January 13, 2013 where stakeholders submitted their comments. Now this is been on the CDSCO website for a while. We hope the review timeline is predictable and there will also be a creation of a new subject expert committee, Thate added.

 Although the Prof. Ranjit Chaudhary report is accepted. The office orders are under implementation. One of his major recommendations was on the accreditation of the clinical research sites, investigators and ethics committee, said the ISCR president.

The permission for conducting the human studies are trickling in. Therefore the trials approved are on CDSCO website. This is a clear indication that human studies are not on hold. However, the larger concerns are on compensation guidelines clarity and the review time line predictability. Amendment of the 122DAB is ruled for comments but not for implementation, pointed out Thatte.

Though the Indian clinical trial industry was passing through a wringer in the recent past, it hopes to overcome setbacks and retrieve the lost ground soon. The slow but steady increase in approvals by the Drugs Control General of India (DCGI) office is a pointer to the signs of revival in the clinical trials business. The formation of expert committees on oncology and cardiology to scrutinize fatality reports arising from SAEs during trials is also proving to be a source of solace for the industry.

For the last 22 months, clinical trial industry has been forced to survive in a volatile regulatory environment which had led to a drastic decline in the number of human studies, rue the industry.

From pharma to biotech and herbal companies, all are dependent on human studies because most of their products are ethically promoted and require safety-efficacy data for clearances from the regulatory authority which help medical experts to prescribe drugs.

By insisting that approval of clinical trials from the DCGI office should be within six months, the Union Government has now extended its support to the clinical trial companies. The government has also levied a dialogue fee to be paid to the DCGI by companies if they need to ascertain the status of submissions before the stipulated time of six months.

Since earlier the approval process took a minimum two years, the latest effort by the government can be considered as the biggest support for Indian and global clinical research companies as there is a timeframe for approval and an opportunity to discuss with DCGI, said Prof. Ranjit Roy Chaudhury, Chairman of the Expert Committee on Clinical Trials constituted by the Ministry of Health and Family Welfare.

Further, the government is also mulling a panel of experts to review and assess the New Drug Applications. The pool of scientific experts would be selected randomly from across India to prevent any bias during the evaluation of drug applications.

These two endeavours by the Union government would increase the confidence level of both the Indian and global clinical trial industry. A few more norms are likely to be announced by the government before the month-end,” said Prof. Chaudhury.

Referring to the approval of clinical trials by the DCGI office, he said pharma companies and clinical research organizations (CROs) were facing uncertainty after they submitted drug applications seeking permission to conduct a clinical trial. Now the companies could also approach the DCGI office to ascertain the details of the trial which is put before the regulatory authority for clearance. However, they will need to pay a dialogue fee to find out the status of their submissions related to the human study. In turn the DCGI or the concerned officials in his office could explain to the pharma, biotech and CRO on the exact stage of the approval process, he said.

The centre’s strategic efforts have now helped to create some momentum in the clinical trial space where human studies have come to an absolute standstill. In the last few months, the approvals of applications to conduct human studies are at a faster pace and trials are also taking place, said Prof. Chaudhury.

The sector has been reeling under uncertainty since January 3, 2013, after the Supreme Court slammed the government for its failure to stop illegal clinical trials companies and also for the rise in fatality from human studies. However, with the government gearing up to support the sector, this has given a reprieve for both India and global pharma and CROs. The unpredictability of the duration for approval or response from the regulatory authority was seen to hamper progress of drug research, pointed out Prof. Chaudhury.

On July 22, 2014, Kiran Mazumdar-Shaw, chairman and managing director Biocon Ltd in her capacity as the chairperson CII-Biotechnology had sought the intervention of Prime Minister Narendra Modi to drive the industry at a faster pace.

If India has to claim leadership in the pharmaceutical industry, it is imperative to focus on drug innovation. The current moratorium on clinical trials is hampering the drug development and instead strengthening external competition which is highly undesirable, said Shaw in her letter to Prime Minister Modi early this year.

The medical profession can only be strengthened if it pursues clinical research along with clinical practice. Only when these run in tandem can there be better health innovation and better health outcomes, she had pointed out.

“The concerns of ethics and safety pertained to a few trials should have been investigated and dealt by the regulators. Unfortunately, the entire sector was forced to pay the price because of a few errant trials. Hence there is an urgent need to resume clinical trials ,” said Shaw in her note to the Prime Minister .

Hurdles impacting industry
Despite the fact that it has become essential for the clinical trial companies to have a dialogue with the government to sort out the problems impacting the industry and bring back the fervour of conducting human studies, there is no such move by the industry at present. This is because CROs are not strong and are not united on this move, said Prof. Choudhury.

The Finance Minister Arun Jaitley in his Union Budget 2014-2015 chose to withdraw the service tax exemption on technical testing of new drugs, including vaccines and herbal remedies. Withdrawing the exemption on service tax and enforcing 12.3 per cent levy was viewed by the Indian Society for Clinical Research (ISCR) as a disincentive to undertake human studies in India.

“This has sent a wrong signal to the global community on the government’s commitment to promote research for better healthcare,” said Thatte, According to Philipe Haydon, CEO, The Himalaya Drug Company, India is proving to be a difficult place to conduct clinical trials. Now herbal companies including ours are at the receiving end. We are facing a serious crunch of investigators for human studies which are mandatory since all our pharma products are prescription-driven and require clinical research data to back the effectiveness and wellbeing. On an average, we conduct 10 clinical trials annually which span over four months. The service tax of 12.3 per cent will definitely hit the company’s net earnings.

“It is puzzling and disappointing to see the withdrawal of service tax exemption on drug testing. This is another blow for the clinical trials industry that is already reeling from the ongoing moratorium and regulatory uncertainty,” said Shaw.

A blow to Indian clinical research
ISCR points that the inordinate delay to permit the speedier approval of human studies has now brought down the overall confidence and trust in conducting clinical research in India. The sponsors are hesitant to do research. Investigators are losing opportunities to hone their skills. The local innovation and R&D are seriously impacted. The big impediment to drug access is on the patients as they are not able to get the newer therapies and which is leading to increasing cost of treatment, pointed out Thatte adding that in 2010, 500 clinical trials were conducted but in 2013, it was less than 100.

 Indian experts also point out that in 2010, value of the clinical research in India was pegged at $2 billion but in fiscal 2014 it is less than $ 50 million

Need to kickstart human studies:
ISCR points out that there is need for a multi-stakeholder consultative approach based on science and highlight a commitment to patient safety, ethics and confidentiality in line with per globally accepted practices.

Further, situations unique to India like literacy, socio-economic considerations and social cultural norms which must also be taken into cognizance in the development of guidelines.

There is also need to ensure presence of adequately trained resources within CDSCO. Since public education and awareness not just about clinical research in general but also about the rights and responsibilities of those who participate in a clinical trial, India needs to create an environment where patients have confidence and trust that their participation in a trial is for their own benefit. Therefore, only greater transparency and openness by the regulators will help in restoring trust amongst various stakeholders, pointed out Thatte.