Year : 2013 | Volume
: 4 | Issue : 1 | Page : 46--48
Enough said, it's time to act
Pharma and Healthcare Blogger, Apothecurry
Flat No. 12, Kartik, Road No 12, Chembur, Mumbai - 400 071, India
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Kamath G. Enough said, it's time to act.Perspect Clin Res 2013;4:46-48
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Kamath G. Enough said, it's time to act. Perspect Clin Res [serial online] 2013 [cited 2020 Jul 15 ];4:46-48
Available from: http://www.picronline.org/text.asp?2013/4/1/46/106380
In July, I was at a conference on clinical research in New Delhi that had very interesting participation. For the first time in 14 years of covering the healthcare sector, I saw drug and healthcare industry executives, patient advocates, media persons, and government/quasi-government officials in the same room discussing their concerns about clinical research and showing a willingness to engage on contentious issues.
The conference was organized by a nascent non-profit, non-partisan initiative called PARTAKE aimed at creating public awareness of clinical research, its benefits, and risks. This was the initiative's first attempt at reaching a consensus among various stakeholders on the PARTAKE agenda, goals, and objectives.
Although the agenda was focused on consensus-building, the participants used this opportunity to talk about their concerns around clinical research at the event and on the sidelines.
Patient groups spoke of incomprehensible informed consent forms. A clinical research co-ordinator at a leading hospital said there was no reason for sponsors or sites to wait for guidelines from the government to compensate trial-related injury, that it was a matter of conscience. Drug industry professionals complained of unfair media coverage. A leading scientist from a government laboratory regretted that, in the past, the community had not been fully taken into confidence during the conduct of trials of potentially path-breaking yet controversial medical advancements such as the injectable contraceptive leading to backlash and rejection.
In short, there were no surprises. That's a good thing. For much of the past 5 years or so, the discussion around clinical research in India has been about the problems-voicing them, framing them in context, discussing them threadbare. It seems to me that the country is now ready to discuss and implement solutions.
This is truly an imperative. For who, as things stand today, can answer unequivocally about the state of ethics in clinical research in the country? In the light of media coverage on allegedly botched drug trials, the public might rightly think that they'd be better of betting on individual integrity than on watertight rules and a system to enforce them.
Writing on the Wall
In 2007, my former employer Businessworld magazine published a cover story on clinical trials in the country. "Systemic disconnects in the drug testing process could undermine India's ability to emerge as a key destination for clinical trials," it warned.
My colleague Gina Krishnan and I had initially planned the Businessworld cover as a status report on the industry that had come up around clinical research in the country. The rapid year-on-year increase in the number of trials being undertaken as part of global multi-centric projects suggested that India was gaining acceptance as a credible destination for clinical trials.
Clinical research outsourcing to India was showing promise as a sunrise sector that could contribute meaningfully to the advancement of science and provide access to potentially promising cures early even as it birthed new companies, created skilled jobs, and earned foreign exchange; a sort of nice by-product of India's controversial move toward a stronger patents regime since 2005 that gave innovators greater confidence to send their intellectual property to India.
But could it get there?
We knew that things weren't all hunky-dory. The biggest problem was that the Indian regulatory system was struggling to keep pace with the growth in trials. There were no site audits by Indian government officials or their proxies, and little, if any, monitoring of the functioning of ethics committees by them.
Clinical research organizations (CROs) were audited by sponsors and there were instances of some sites passing muster with the United States Food and Drug Administration. But the absence of adequate local intervention was a concern since it suggested that the sector was being left to self-regulate. As we spoke to the various stakeholders-CROs, sponsors, bioethics professionals, and so on-the nature of the problem became evident.
It was a classical case of opportunity unfolding in the middle of shortage.
We heard of sought-after investigators bargaining for higher subject recruitment fees knowing that their breed-who understood how to conduct clinical trials-was rare in the country. Of young relatively inexperienced professionals tasked with monitoring trials on site and then, within a year, being poached by a different CRO for a higher salary.
Of ethics committees struggling with the number of proposals coming their way. Of the moral dilemma posed by subjects with little access to healthcare potentially seeing a carrot in the free care, in the extra minutes that a doctor would spend with them and in the opening to jump the queue in the crowded outpatient departments of public hospitals. Of the possibility of subjects not entirely understanding the informed consent form yet participating because they thought their doctor wanted them to.
And yet, the number of trials offshored to India continued to grow on the back of three main attractions-low costs, an English-speaking workforce, and a large and diverse patient pool that could cut time-to-recruit. How long could that last, we wondered?
The rider, of course, is that there was nothing to suggest that this was happening everywhere all the time. Nor were these problems insurmountable.
There were two big concerns, however. First, even as India was strengthening its rules and regulations, subjects were vulnerable to exploitation or inducement. Second, even if trials were conducted in tune with the most stringent guidelines, there was ample opportunity for naysayers to point fingers.
What was heartening, though, was that there were good people within the system who were seized of the concerns and wanted a change for the better. The government was responding. For the first time that year, India had an online clinical trial registry; guidelines including those that required investigators to declare conflict of interest were being updated; there were plans to beef up regulatory strength to conduct inspections.
But what followed is more a tale of missed opportunities.
The Cup and The Lip
In 2008, the Drugs Controller General of India (DCGI) conducted its first audit of a clinical trial of (then) Wyeth's trial of Prevnar 13 pneumococcal vaccine. A baby had died. She had not received the trial vaccine, but the on-market one to which it was being compared. A report in The Wall Street Journal observed that the audit found fault with the trial's supervision and not the vaccine, itself. But the handling of the results of that inspection found a lot to be desired.
For one, the DCGI's office sent out patchy, confusing messages through selected media instead of simply publishing on its website its warning letter and responses from the various parties (CRO, sponsor, site, investigator), and publicizing action taken. It did not make the report of its findings available to the public on its website.
It was an opportunity to inspire confidence that was thoroughly wasted. In an article titled, "Why the Secrecy?" that I wrote in Businessworld, experts observed that it was important to inform public debate on clinical research-and controlling or selectively leaking information was not the way to do it.
For in the absence of honest and open communication, the world feels free to imagine the worst.
Compare to this how the death of a school girl in the UK after receiving approved cervical cancer vaccination had been handled by media and public health authorities around the same time. The cause of death was identified within 48 hours and, in this case, it had nothing to do with the vaccine. Large-scale panic had been averted by timely and honest communication by health authorities thus helping the media to do its job.
Subsequent cases of allegedly botched trials in India have resulted in similarly inadequate or confused communications from health authorities with predictable results. For instance, a cervical cancer vaccine demonstration study on tribal girls in Andhra Pradesh was investigated after allegations of trial-related deaths. The media put out parts of the final report that found that informed consent had not been properly obtained but concluded rather incomprehensibly that no one was to be blamed. The report itself is not easily available.
And even as sponsors and clinical research organizations have wrung their hands at the state of affairs, few would willingly come forward to transparently reveal details of audits and investigations involving them. This makes those who don't complicit in the system's failure.
In the meantime, the process that began 4 years ago to tighten oversight has lost pace. The ministry of health's rules for ethics committee registration and clinical trial compensation are still drafts. At the time of writing this, the ministry had belatedly announced that it would soon make it compulsory to video-tape informed consent. Since the Wyeth audit, there's little information on inspections of other trials and their findings. Did the DCGI stop audits? Or have its inspectors found nothing wrong in any of the inspected trials?
There are other ethical dimensions to performing trials in a developing country where large swathes of people cannot afford costly new medicine. It is not unrealistic for subjects to wonder if they will continue to receive the drug if it works and is commercialized, even if they can't afford to pay full price. As India sorts out the "hygiene" issues around clinical research, bigger issues are looming on the horizon that need to be tackled, in parallel.
Notwithstanding media reports on trials allegedly gone awry, we still don't have any reason to believe that India is a hotbed for unethical clinical research. But nor can it be said with certainty that nearly every trial is done by the rulebook.
As a result, clinical research in India is in the dock-guilty until proven innocent. Apart from those who have a commercial interest in its conduct (drug companies, CROs, hospitals) and a handful of patient groups, by no means hugely influential, it appears to have few votaries. In the meantime, regulatory approvals to conduct trials have slowed down considerably though no one is quite sure whether this is meant to have a salutary effect on the ethical conduct of approved trials or is only a knee-jerk reaction to all the controversy.
It's time to end this blow-hot, blow-cold relationship with clinical research. Clinical trials are the only scientific way known to man to bring new cures and interventions into the market. Besides, they can provide early access to experimental cures to terminally-ill patients who have exhausted all options.
India has to decide unequivocally whether it wants to be part of the process. If it does, the state not only has to tighten oversight but also communicate proactively, openly and transparently as proof. Every audit must have closure with the findings and action taken available to all. The guilty should be punished. It may be that on issues such as informed consent some laws or guidelines will have to be customized to meet local requirements much like India tailored its patent laws.
The longer India dithers, the fewer supporters clinical research is likely to have in the country.