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Friday, December 20, 2013

Reforming medical research: Some progress, but huge obstacles remain

8:14 AM
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On Thursday, as a kind of holiday gift, British psychiatrist and epidemiologist Dr. Ben Goldacre posted online a free update chapter to his 2012 book,

He calls the new chapter "a fun romp through the changes that have happened over the past year or so, starring the many ethical professionals in pharma and medicine who have tried to push things forward, and some very shameful denialism from people in positions of 'leadership.'"

I'm not sure about the "fun" part (although Goldacre is an exceptionally accessible and often quite humorous writer). The chapter is certainly a must-read, however, for anybody who is following world-wide efforts to reform the way medical treatments are researched, marketed and delivered.

More transparency

On the "pushing forward" side of things is the launch of the "All Trials Registered, All Trials Reported" campaign, which calls for medical researchers to disclose all their clinical trial data — not just favorable data about a drug or other medical treatment.

Right now, about half of all clinical trials results never get published. A major reason, claims Goldacre (and many others), is because medical drug and device companies — as well as academic researchers — routinely withhold any clinical trials that turn up negative data.

Negative data is not good for business — or for academic careers.

Most drug and medical device companies therefore have been aggressively opposing clinical-trial transparency. One industry lawyer told Goldacre quite bluntly — and seemingly without any sense of public accountability — that "we pay for the trial to be done, [so] it should be our choice how that data is used."

But, reports Goldacre, "it has not all been denial and gloom." Last spring, in what has been All Trials' most impressive victory to date, the pharmaceutical giant GlaxoSmithKline signed on to the campaign. The company pledged that it would release all data from its clinical trials within a year of each trial's completion — and it would do this retrospectively to include the company's past trials.

'Huge problems'

Goldacre does a great job in an "epic footnote" to his update chapter of summarizing the "huge problems" that continue to plague clinical research.

Dr. Ben Goldacre

Dr. Ben Goldacre

There are the "harms inflicted on patients by our over-reliance on surrogate outcomes  — rather than real-world outcomes like death," he notes, and "the problem of trials comparing new drugs against hopeless existing treatments, in order to get an impressive result."

"This practice is important: it creates uninformative evidence, but it also exposes trial participants to unnecessary harm," Goldacre explains. "One editorial, accompanying further research on the topic, was unambiguous: 'In fifty-six out of sixty-three trials involving patients with highly active rheumatoid arthritis, potentially helpful treatments were withheld from 9,224 out of 13,095 patients randomized to the control arms. Why? Because placebos or treatments known to be ineffective were used as controls.' The title of this editorial was unusually direct about the impact on patient care: 'Blood on Our Hands: Seeing the Evil in Inappropriate Comparators.'"

Goldacre also cites "the problem of drugs being tested in small, brief trials."

"A paper in PLoS Medicine from March 2013 puts hard figures on this," he writes. "From a representative sample of two hundred newly approved medicines, each was studied on average in only 1,708 people before approval; and one in five drugs for long-term use failed to meet the guidelines' recommendations. These guidelines, to be clear, are weak in themselves, requiring only that three hundred people should be followed up on the drug for more than six months: for effectiveness on long-term outcomes, this is plainly inadequate."

Then there's the troubling issue of research that was never done on drugs and other treatments that are in wide use. "A paper published in August 2013, as this chapter went to press, explains that for half of all the recommendations in the current major cardiology guidelines, the level of evidence is only 'grade C,'" Goldacre points out. "This is astoundingly poor for one of the biggest specialties in medicine."

Biased marketing

Of course, transparency problems continue after the clinical trials are over, when the drug companies market their products to doctors.  Writes Goldacre:

In April 2013 a paper was published in the Journal of General Internal Medicine, reporting on a survey of 255 doctors, in four different countries, describing 1,692 visits from drug reps. Less than 2 per cent of visits gave "minimally adequate safety information," and at only 6 per cent of visits were serious adverse events mentioned, even though 45 per cent of promotions were for drugs with 'black box' warnings.

In the same month, President Barack Obama was attacked for his "Academic Detailing" initiative in the USA. This is a new project, designed to run in parallel to the system of  "drug reps" (called "detailing" in the US): clinician consultants visit doctors, nurses and pharmacists, disseminating unbiased summaries of evidence about which treatments work best. Pfizer CEO Ian Read said — with no shred of irony — that the Academic Detailing project is a waste of public money, because government has a "conflict of interest" when it disseminates evidence to clinicians.

Despite all these problems (and what I've included here is only a sampling of those discussed in Goldacre's update chapter and, indeed, in his book), there are signs that things may be getting better.

"There is a huge amount happening right now: inquiries in multiple countries, European legislation, a groundswell of popular opinion, a barrage of new research findings, cultural shifts in regulators, isolated individuals in industry showing leadership, and more," Goldacre points out.

"But this has all happened before, without delivering success," he adds. "The window will only open briefly, and there are many, many people trying to wrestle it shut. For the good of patients, for the reputation of medicine, and for the reputation of the pharmaceutical industry, we have one new chance, right now, to deliver real change. I hope you can help us to take it."

You can read Goldacre's new chapter on his Bad Science blog.

Susan Perry 20 Dec, 2013


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Source: http://www.minnpost.com/second-opinion/2013/12/reforming-medical-research-some-progress-huge-obstacles-remain
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