26 new drugs permitted for sale without trials in India. Between January and July of 2012, the Indian drug authorities approved 14 new drug molecules but only 9 had undergone any clinical trials.

NEW DELHI: Notwithstanding strong warnings by the parliamentary standing committee on health, new drugs continue to be approved for marketing in the country without holding any clinical trials on Indian patients to test their safety and efficacy. Sources in the Health Ministry admit that as many as 26 new drug molecules have been approved since 2010 without testing them through drug trials on local populations.

While eight new drug molecules of biologicals and non biologicals were approved by the country’s apex drug regulator, the Central Drugs Standard Control Organisation (CDSCO), last year, two have already been allowed for sale so far this year. As many as 13 such new drugs were approved in 2010 and three more were approved in 2011. Officials of the health ministry say that new drugs have been approved without clinical trials after taking adequate caution.

They said such drugs are the ones used in medical emergencies and where trials are not possible in the country due to less number of patients and in cases where diseases are rare.They said that it is only after expert opinion that such drugs are being approved. Importantly, the approval to 26 new drugs sans local trials comes within two years of the parliamentary panel exposing how 38 new drugs were approved without trials on Indians between January 2008 and October 2010. The committee had while coming down heavily on the drug controller for allowing untested drugs to be used in India said that many such new drugs did not fall in the category of medicines meant for medical emergencies.

The report had focused nation’s attention on the poor state of drug regulation in India and sought immediate corrective measures. Following the report, the health ministry has introduced several new measures aimed at ensuring efficacy and safety of drugs. The CDSCO has also written to states to prove within 18 months the safety and efficacy of all such fixed dose combination drugs which have been approved directly by states without seeking prior approval of the apex drug regulator.The ministry is ready with a new Drugs and Cosmetics Act which deals with clinical trial regulation in a separate chapter.

What started as a rare reporting subject only a few years ago has become a frequent fixture for newspapers and magazines  ethics in clinical trials in India.

What started as a rare reporting subject only a few years ago has become a frequent fixture for newspapers and magazines — ethics in clinical trials in India.

Unfortunately for the industry, most of the coverage focuses on the ill-effects of doing investigational clinical trials on the Indian population. Examples abound of clinical trials by global companies in remote locations on gullible patients, leading to deaths or long-term serious adverse events.

Though dramatised out of proportions by television channels, much of the information in public domain is correct. As a consequence, although the clinical trials industry has bright prospects, the edge is gradually getting blunted.

Who is to blame?
Sponsors and clinical research organisations (CROs) are smart business associates. It would be hard to corner them for violations as they do follow the norms and submit to the regulatory agencies piles of documentation involving elaborate consent forms signed and accepted by trial subjects.
Investigators — the bridges between CROs and patients — are the holy grails, claiming to follow rules to the tee.

Regulatory agencies cannot be faulted as enquiries or investigations — mainly constituting government representatives — may not yield much to nail them. With a sharp rise in the number of trials in India, overburdened ethic committees that draw independent representatives from various fields are seen more as nominal signing authorities. And many critics question their independence in allowing trials on drugs that may be perceived risky to patient safety.

In all the divergent clashes of stake holders, the big loser is the patient.

Most cases of violation of good clinical practices that have stood out sourly are from India’s small towns or rural areas. Some NGOs claim patients, in their fight for survival on affordable treatments, have often signed on consent forms without going through the details involved on being tested on an experimental drug. More alarming is the fact that in many cases, the countersigns found are of doctors and not independent witnesses. With all the faith that a patient poses in his doctor for medical treatment, that act reflects poorly on the profession.

With all the legal strictures at play, the big question to be pointed to the regulators is how approvals are granted to brazenly faulty trial protocols. Does India have the right machinery ready to allow or investigate the minute nuances of clinical trials? Are there examples of strict punitive action against sponsors, CROs, investigators or ethics committees where clinching evidences are found? Is merely registering for clinical trials sufficient to ensure patient safety? How effective are the compensation norms for patients affected by trials?

While there are legitimate concerns on the quality of clinical trials in India, we have to also admit that clinical trials on drugs are necessary to investigate new drug discoveries and bring in latest treatments. And for that there are a handful of serious players who seem to be following the ethical practices. For the fault of a few, can all the investigations be treated harshly?

As it stands now, select CROs vow to follow all the norms in the book but having faced the flak from past errors in approval processes, regulatory agencies are in a pause mode for long. For those with mounds of luck, trial approvals have taken over eight months and for others there an eerie uncertainty remains. Being cautious in granting approvals is ideal but to keep the industry on its toes without elaborate reasons is an ominous signal to exit their projects in India.

That would not only be enormously damaging and negative for the Indian industry, but also, and more importantly, the move may not be beneficial for the Indian patients. For any drug to be efficacious on the Indian population, it is important to have the right representation in global trials for cutting edge products.

At the same time, there cannot be anything more unfortunate than that a drug meant to save lives leads to controversial deaths. And there cannot be a lasting solution unless all stakeholders make a serious commitment to patients by following ethical international guidelines. To risk the lives of helpless patients merely to push commercial interests is nothing short of an act of crime. The guilty must be debarred and punished and that should be the utmost task of authorities. The three phase clinical research lasting for three to four years involving thousands of human volunteers in multi locations is the most costly part of new drug discovery for a pharmaceutical company. Any of the potential drug candidates can be abandoned during the trial period if the adverse drug events are beyond the acceptable limits. It is a high risk activity requiring millions of dollars and pharmaceutical companies usually make sure that trial reports reaching the regulatory authorities are favourable. No new drug can be approved for marketing without submission of trial reports and their scrutiny by the regulatory authorities. India has emerged as an attractive destination for clinical trials since 2000 as the MNCs realised that the country has a diverse range of patient pool and a relative cost advantage for human studies. Apart from top MNCs like Pfizer, GSK, Novartis and Novo Nordisk, a large number of contract research organizations had thus got into clinical trials in India for more than ten years.

While India established itself as a global destination for clinical trials, unethical practices in this business also started emerging slowly. This was mainly in matters like patient recruitment, taking informed consent, bypassing ethics committees,submission of trial data,etc. The weak regulatory system governing clinical research in the country has emboldened the companies and CROs to do this. It is this situation that caused several deaths and fatal injuries during trials in the last three to four years. An inquiry conducted by the Union health ministry in May 2011 thus revealed that 671 deaths occurred during trials conducted by different companies in 2010. And only in three cases, some compensation was given to the relatives of the victims by the pharma companies or CROs. It is from here the problems started for clinical research in the country. The Supreme Court took a serious note of this state of affairs and had made some scathing remarks on the health ministry’s neglect in this matter. The health ministry subsequently notified the rules and procedures for fixing compensation to the victims of trials giving legal backing to the existing guidelines. The rules thus notified by the government under Drugs & Cosmetics Rules had put the DCGI as the final authority in the matters relating to the compensation in the cases of deaths and injuries during trials. DCGI also became strict in granting approvals for clinical trials. In case of compensation to victims of trials, MNCs and CROs should not have reasons to complain. That is a standard practice anywhere in the world. What is actually disturbing the pharma companies is the reluctance of DCGI to grant approvals for trials. And it is a fact that from 2012 number of approvals for drug trials came down sharply. This should not have happened. What is required is effective monitoring of trials and that must be possible now by making registration of ethics committees compulsory. The office of the DCGI should not, therefore, unreasonably hold up granting of approvals for trials.

US agency confirms suspension of India clinical trials

NIH says recent clinical trial regulations in India have affected some its studies

New Delhi: The National Institutes of Health (NIH), the state-owned medical research agency of the US, has finally confirmed that it has put on hold all clinical trials in India, following the health ministry’s efforts to tighten related laws.

“Recent clinical trial regulations in India have affected some NIH studies,” the NIH said in a 19 July statement. “Some trials have stopped enrolment and some others have been postponed.”

The NIH, an arm of the US health department, has cancelled approximately 40 ongoing clinical trials in the country, Mint reported on 11 July. NIH had declined comment at that time.

The health ministry relaxed some of the new rules it put in place, after realizing that these could effectively kill India’s growing clinical trials industry, according to a note posted on its website on 10 July. These tighter laws were instituted following the Supreme Court’s intervention.

The clinical trials business in India is estimated to be worth around $500 million (Rs.2,970 crore), according to researcher Frost and Sullivan, which projects that it will grow to $1 billion by 2016. Industry experts estimate a loss of $150-200 million in the past six months on account of regulatory changes.

After industry lobbying, the ministry has already relaxed norms—one concerning compensation and another that said the tests could have only the desired or intended effects, and no other.

India approved 475 clinical trials for “new chemical entities” not used as drugs elsewhere in the world, according to documents submitted by the Drugs Controller General of India in the Supreme Court, between January 2005 and June 2012.

The documents said that 11,972 adverse effects, excluding deaths, were reported in the period, with 506 of these being directly attributable to the trials. They put deaths from trials at 2,644 in the past five years.

In a 3 January ruling, the apex court revoked the powers of the Indian drug regulator to approve trials for new chemical entities, placing the responsibility on the health secretary, who was asked to personally vet all approvals. Since then, only six trials had been approved until this month, when the ministry cleared 50 trials at one go.

“We believe the protection of research participants involved in clinical trials is an ethical imperative and we commend the substantial efforts being made to review the oversight of clinical trials in India,” the NIH said in its statement. “We are following developments surrounding the amendments to the Drugs and Cosmetics Rules, and are hopeful that additional information and guidance surrounding their implementation will pave the way for our continued joint endeavours.”

Clinical trial of untested drugs must be regulated: SC

Clinical trials of untested drugs on humans require certain mandatory standards to be followed, the Supreme Court said on Friday while directing the government to put in place a mechanism to monitor them.

The apex court directed the Centre to convene a meeting of Chief Secretaries or Health Secretaries of all the states to frame a law for regulation of clinical trials of drugs by multinational pharma companies.

A bench of justices R.M. Lodha and Madan B. Lokur granted four weeks time to the Centre to convene the meeting and for framing rules.

“Certain standards and protocol should be followed while conducting clinical trials of drugs on humans. We are concerned about human life,” the bench said, asking the Centre to consider suggestions of the National Human Rights Commission on the issue.

“How do you monitor that clinical trial does not result in death and there are no side effects. There should also be proper compensation,” it said.

It said that there should be an oversight committee to monitor such trials and directed the Centre to file an affidavit by September 24 after consulting state governments.

Additional Solicitor General Siddharth Luthra submitted that the Centre is considering making amendments in the Drugs and Cosmetics Act by introducing penal provision for any violation.

Earlier, the apex court had said that uncontrolled clinical trial of drugs by multinational companies was creating “havoc” and slammed the Centre for failing to stop the “rackets” which caused deaths.

Observing that the Government has slipped into “deep slumber” in addressing this “menace”, the court had earlier ordered that all drug trials will be done under the supervision of the Union Health Secretary.

In an affidavit, the Centre had admitted that 2,644 people died during clinical trials of 475 new drugs between 2005 to 2012.

“Serious adverse events of deaths during the clinical trials during the said period were 2,644, out of which 80 deaths were found to be attributable to the clinical trials,” the affidavit had said.

“Around 11,972 serious adverse events (excluding death) were reported during the period from January 1, 2005 to June 30, 2012, out of which 506 events were found to be related to clinical trials,” the Centre had said.

The court was hearing a public interest litigation (PIL), filed by NGO Swasthya Adhikar Manch, alleging large-scale clinical drug trials across the country by various pharmaceutical firms using Indian citizens as guinea pigs in those tests.

The NGO had alleged that the clinical trials by several pharmaceutical companies were going on indiscriminately in various states.