There will always be inherent tensions between the commercial objectives of a privately-owned pharmaceutical industry, its contribution to the national economy and the wider goals of public health, writes Peter Mansell.
That is the model we have and, in many respects, it has served us well. Even last year’s report by the House of Commons Health Committee, which had some harsh things to say about the industry and the regulatory regime it operates under, acknowledged that medicines “contribute enormously to the health of the nation,” while driving the UK’s third most profitable economic activity after tourism and finance.
So to suggest pharmaceutical companies should no longer test their own products is to say those tensions are no longer sustainable: that the industry has crossed a line. For Fiona Godlee, editor of the British Medical Journal, the recent pile-up of drug safety disasters and claims of sharp practice in research and development provides ample pretext. For industry, that kind of system would be a step back into the Dark Ages.
Godlee’s proposal comes in a recent editorial that touches on the Vioxx (rofecoxib) debacle and the perceived data manipulation or flawed analysis – by sponsors and regulators alike – that muffled the potential risks of suicide with selective serotonin reuptake inhibitors such as GlaxoSmithKline’s Paxil/Seroxat (paroxetine).
Godlee fears the two traditional filters between public health and the commercial interests of industry – drug regulation and journal peer review – are no longer up to the task. Regulators stand accused of cosying up to pharmaceutical companies, poor transparency, sloppy post-marketing surveillance and a preference for efficacy over safety. Meanwhile, she says, the journals are losing their grip on objectivity, under pressure for newsworthy content and reprint revenues.
A central clinical trial pot
A radical solution, Godlee proposes, would be to take the clinical development process out of the industry’s hands altogether. Drug companies “should not be allowed to evaluate their own products,” she writes. “To get their products licensed they would contribute to a central pot for independent, publicly-funded clinical trials.”
The editorial does not delve any further into the logistics of such an exercise, nor its likely impact on industry’s willingness to engage in costly research and development. Moreover, Godlee admits the idea is not a new one. She cites comparable suggestions by Des Spence, the Glasgow GP and familiar industry critic, and by Marcia Angell, former Editor of the New England Journal of Medicine.
Angell became the favoured scourge of all things pharmaceutical in the US on the back of her book, The Truth About the Drug Companies: How They Deceive Us and What To Do About It. Among her remedies for the runaway greed, corruption and creative exhaustion she perceives in the industry is a federal Institute for Prescription Drug Trials within the US National Institutes for Health, which would manage clinical studies by contracting them out to independent researchers in academic medical centres.
A PR crisis
The drug industry itself is all too aware of the public relations crisis that has mushroomed around Paxil, Vioxx and other bete noires. Pharmaceutical associations and companies have been making strenuous efforts to embrace – or, at least, be seen to embrace – transparency by turning their clinical trial data over to public scrutiny. The Association of the British Pharmaceutical Industry was ahead of the field in this respect, launching a website in May 2003 where member companies are encouraged to register all Phase III trials involving UK patients that have formed part of a licensing application.
These pre-emptive strikes were dismissed in some quarters as too little too late. The Commons Health Committee, while welcoming plans for a worldwide clinical trials register, subsequently announced by the European Federation of Pharmaceutical Industries and Associations, International Federation of Pharmaceutical Manufacturers and Associations, Japan Pharmaceutical Manufacturers Association and the Pharmaceutical Research and Manufacturers of America, expressed concern that having a system maintained by industry “will not inspire confidence from either the public or healthcare professionals.”
Yet the committee’s recommendation that an independent body should be responsible for the register, with comprehensive trial data lodged there as a condition of marketing approval, was parried in the government’s response to the report. And, for all its recognition that the current system of clinical testing “provides ample opportunities for bias,” the health committee did not even come close to suggesting this system should be dismantled.
Instead, it settled for fine-tuning, such as encouraging the Medicines and Healthcare products Regulatory Agency to “work with the pharmaceutical industry and outside experts to design clinical trials that establish the real therapeutic value of new medicines using measures that are relevant to patients and public health.”
A lack of enthusiasm
Nor is there any sign of government enthusiasm for a wholesale review of clinical trials’ funding and management. In its evidence to the health committee, the UK government said it “believes that the current model – whereby medicines are developed by the private sector in response to what they perceive to be the demand of healthcare systems – is more effective and efficient than alternatives that could be considered (such as nationalising the drug industry, or by government directing the research that the industry should undertake).”
But are Godlee and her ideological predecessors really so far out on a limb? After all, the evidence of data manipulation, selective trial reporting and their potentially fatal consequences has probably never been as available and as damning as it is now.
While the mainstream media welcomed her expose of pharmaceutical malpractice with open arms, Marcia Angell has come in for some heavy flak, both from the pharmaceutical industry and assorted pundits more or less sympathetic to her cause.
Henry Miller, a physician, former Food and Drug Administration official and fellow of the Hoover Institution and the Competitive Enterprise Institute, claimed Angell’s “proposals to, in effect, nationalise the American system of drug development reflect almost inconceivable naivete.”
Writing in Nature Medicine, Ralph Snyderman, a visiting Professor at the University of California, San Francisco, who is on the boards of Procter & Gamble, Axonyx and Cardiome Pharma, said he strongly agreed with a number of Angell’s concerns, particularly around the manipulation of trial data. But her concept of an Institute for Prescription Drug Trials was an “unworkable proposal” that would “grind drug development to a halt.
Industry could not afford to develop drugs, then wait for an academic peer review process to give them access to a queue for clinical trials,” Snyderman commented. “Moreover, there is an insufficient clinical trial infrastructure in academic institutions to support the volume of clinical trials needed.”
An industry backlash
There was a similarly robust response from the ABPI in the UK. On a purely practical level, it pointed out, clinical trials were a global undertaking, carried out in multiple countries by multinationals for “global patients.” Any change in the infrastructure of clinical development would need to take this into account. Moreover, around one third of trials in the UK are already funded by the government or academic institutions, which constitutes “important and valuable work that supports general understanding of disease and helps keep the UK as a vital centre of biomedical research,” the Association stated.
Richard Ley, ABPI’s Head of Media Relations, said the kind of centralised system envisaged by Godlee et al had never worked in any country in the world. “How many [innovative] medicines came out of Russia?” he asked.
Turning over commercially driven trials to an independent public agency would create a “massive” bureaucratic burden in a system that was already “quite cumbersome,” Ley contended. Companies would simply look elsewhere to conduct their research – to the US, for example, which attracts “vast amounts” of R&D.
This comes at a time when the pharmaceutical industry has been working hard with the government to boost declining clinical trial investment in the UK. Their efforts are now starting to bear fruit, but any fundamental change to the system could scupper that progress “virtually overnight.”
Ley denied the industry had its back to the wall over allegations of trial manipulation. Pharmaceutical companies wanted the right data for both commercial and ethical reasons, he insisted. If these data were distorted, the companies would be found out. And in a “long-haul” business such as drug development, industry could not afford the ensuing damage – either legal or perceptual.
Whatever the challenges to the status quo, “we are actually producing life-saving medicines,” Ley commented. One quarter of the world’s best-selling drugs originated in the UK and that is “something to be proud of.”