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Making all clinical data public is vital for better medical care

An article published in the journal of the British Medical Association, BMJ, earlier this week illustrates a devastating problem with the “evidence base” in the academic medical literature. A large proportion…

A large proportion of drug trial data never gets published, skewing our picture of drugs' effectiveness and safety. opensource.com

An article published in the journal of the British Medical Association, BMJ, earlier this week illustrates a devastating problem with the “evidence base” in the academic medical literature.

A large proportion of drug trials, particularly those sponsored by pharmaceutical companies, never get published, skewing our picture of drugs' effectiveness and safety.

But it’s not all bad news; a UK initiative called AllTrials is seeking to remedy the situation by calling for the results of all clinical trials to be published.

A festering problem

Research published in 2010 showed results unfavourable to sponsored drugs are less likely to be published, or selectively published to put a favourable “spin” on poor results.

And internal pharmaceutical industry documents released from court cases show concealment of data is a widespread practice.

A colleague and I assessed such documents about psychiatric medications from five pharmaceutical companies. The papers suggested widespread overstatement of benefits and understatement of adverse effects.

Other researchers have found similar problems with different drugs.

Journals respond

In response, some medical journals voluntarily agreed to publish only studies registered on a website of the US National Institutes of Health, ClinicalTrials.gov.

At least studies with unfavourable results would not be “buried” by drug companies. But the BMJ article confirms that many registered studies still don’t get published.

Chief editors of major medical journals have condemned the status quo. Marcia Angell of the New England Journal of Medicine has called industry-sponsored research “a broken system”; Richard Horton of The Lancet answered the rhetorical question of his editorial “How tainted has medicine become?” with “heavily, and damagingly so"; and the BMJ’s Fiona Godlee told a British parliamentary committee that “drug companies should not be allowed to evaluate their own products.”

The previous chief-editor of the BMJ, Richard Smith has offered a radical solution – journals should stop publishing drug trials and instead provide expert critiques of the full data and methodology of trials posted on regulated websites.

The AllTrials initiative

The AllTrials initiative aims to make that vision a reality. It intends to make the (de-identified) results and methodology of drug trials available to independent researchers so journals can publish in-depth articles based on all of the full data.

In 11 months, the campaign’s petition has gathered over 59,000 individual signatories and over 400 medical and health-care organisations. These include many British medical colleges and learned academic medical science institutions, such as the Cochrane Collaboration and the British National Institute for Health and Clinical Excellence (NICE).

Although the campaign is progressing slower outside the United Kingdom, it is managing to get some traction internationally.

The World Association of Medical Editors (WAME), the South African Medical Research Council and the Canadian Agency for Drugs and Technology in Health have signed.

Perhaps with an eye to the future, the International Federation of Medical Students Associations, the American Medical Students Association and the Australian Medical Students Association have gazumped their senior colleagues and also signed.

Trouble in Europe

The European Medicines Agency (EMA) – equivalent of America’s Food and Drug Administration (FDA) or Australia’s Therapeutic Goods Administration (TGA) – adopted a similar policy in 2010, and decided to release much of the drug trial data in its possession.

The EMA’s policy is currently stalled by a European Court injunction because of a lawsuit by two pharmaceutical companies. And Europe’s pharmaceutical industry body has threatened a “series of lawsuits”.

The ethical issue here has more to do with health professionals, journals, and governments; pharmaceutical companies need to make a profit. Nonetheless, GlaxoSmithKline has signed the AllTrials petition.

The way forward

Ultimately, people who practice and teach medicine, surgery, pharmacy, and other health-care professions, as well as regulatory and government all rely on good evidence to make the best decisions for our collective health.

As the chief editors of prestigious medical journals are now telling us, the current system is broken and unable to deliver evidence-based medicine. The implications of this are profoundly negative for both our health and financial well-being.

The AllTrials petition has garnered impressive support in just under a year. But more international support is needed for its aims to be fully implemented. A healthier, better-informed future depends on its success.

This article has been amended. In its previous version, it stated that LEO Pharma and GlaxoSmithKline had signed the AllTrials petition, but the text has been corrected to reflect that only GlaxoSmithKline has signed.

According to the AllTrials website, LEO Pharma has committed to greater transparency.

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19 Comments sorted by

  1. Mark Snashall

    Statistician

    As a statistician working in the pharma industry I have to say that this is definitely needed. The problem is not so much that the studies are analysed incorrectly but that they are reported/published without the study as a whole being taken into consideration. I myself have seen medical writers trawl through pages of statistical output looking for p-values less than 0.05 and basing conference posters on only the "significant" results found.

    We also need to have greater statistical input into…

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    1. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to Mark Snashall

      Thankyou Mark,

      Good points from someone in the know, and they tally with what the internal industry documents we analysed had to say.

      We do need long term safety studies. One organisation feels a good way to get some of this data is simply to have patients as well as clinicians (who seldom get around to reporting adverse events) report adverse events - see https://www.rxisk.org/Default.aspx

      Also there is dire need for more independent govt/university funded studies - but a tough ask in a world where neo-liberal economic privatisation policies still rule.

      AllTrials offers the kind of rich data though that would mean the cherry picking of the <.05 results was seen in context and we could no longer be hoodwinked in that sense.

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    2. Chris Williams

      logged in via LinkedIn

      In reply to Peter Parry

      I wonder how much of this could be resolved if journals were to actually check the contents of prospective trials registrations.

      One critical point is that 'big pharma' are not solely to blame for this sort of publication bias. In fact it seems they are not even the main culprits. https://theconversation.com/register-all-trials-report-all-results-its-long-overdue-11603

      The All Trials agenda is a great initiative but not just for the 'big bad' pharma companies.

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    3. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to Chris Williams

      Good point Chris and I hope I conveyed that the problem is complex and not just the fault of Big Pharma. I think I focused on Big Pharma here because their own internal documents show they have milked the system quite deliberately.

      But Pharma companies are torn between commercial ethics in a capitalist system to maximise profits for their shareholders versus scientific and medical ethics to tell the public and academic and clinical medicine the truth. On the other hand medical journals, academic…

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  2. Craig Myatt

    Industrial Designer / R&D

    This is a classic problem of industry influence over science, which is prevalent with large concentrations of market power. Very similar dynamic in relation to climate change and fossil fuel industries. Perhaps a good solution in the pharmaceutical industry could be applied to other science-industry relationships, for example environmental reporting for firms, an area of common industry influence/bias in reporting on science.

    Could ISO develop a range of standards to ensure probity for science-industry information flows?

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    1. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to Craig Myatt

      Yes Craig, good point.

      When I've discussed or presented these issues with psychiatry/medical colleagues - we often end up wondering just how distorted the science is in other fields where commercial interests dominate.

      In health care - AllTrials could eventually be extended beyond drug trials to surgical devices, psychotherapies, physio, herbal remedies etc etc

      Similar regulated websites of data could presumably clean up the evidence base in many other fields too.

      In the end the full data available to all with expertise in assessing it is the ultimate in peer review.

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  3. Alan Fien

    Engineer

    A propos the vigorous objections of the National Heart Foundation to the ABC Catalyst program on statins, in which a number of researchers made claims of overprescription and a lack of evidence of beneficial effects on longevity, has the Heart Foundation signed up to support AllTrials?

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    1. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to Alan Fien

      It is not my area - but it is sad that there can still be controversy over statins. A good case can be made that if we'd had AllTrials access to data for the past couple of decades that we would have more clarity on this issue.

      The Australian Heart Foundation is not yet on this list - http://www.alltrials.net/supporters-list/

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    2. Donald Runcie

      retired

      In reply to Alan Fien

      Alan, the Cochrane Collaboration recently published a review concluding that the use of statins was justified. The ABC program Catalyst made no mention of this.

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  4. Paul Prociv

    ex medical academic; botanical engineer at University of Queensland

    I agree. Most practising clinicians have neither the time nor expertise to evaluate critically the mass of data and statistical analysis presented in reports of large clinical trials, and are reduced to depending entirely on the assurance of authors and other "experts" with regard to the validity of conclusions. Far more than p-values is involved. This means that publishing all such studies in general medical journals might be a case of over-kill.
    On another matter: regarding "long-term" complications, for how long should a study population be followed before the trial can end? Some side effects of medications might show up only after many years of treatment; expecting 100% perfection, by detecting all these, would be prohibitive for any meaningful research.

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  5. John Holmes

    Agronomist - semi retired consultant

    This is not just a problem with pharmaceuticals and medical R&D, pesticides, animal products as well as advanced breeding details - GMO's et al, should also be included. Bit of a problem re commercial in confidence data, yet regeneration data could also be included.

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    1. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to John Holmes

      Yes John, for real science we need transparency all over the place. However commercial confidentiality does has a place - in the R&D phase - but once a product is going to come into use for the general public - for you, I and our loved ones, and the environment - there is no excuse not to have full transparency.

      Otherwise there is simply no such thing as "Evidence-based Medicine" or presumably evidence-based agriculture, engineering etc etc - only "Marketing-based XXX".

      I watched ABC's recent controversial Catalyst episode on statins. Without buying into the argument over how beneficial or otherwise statins are (as it is not my field) - I would have to strongly agree from my experience in psychiatry - with Prof John Abramson, public health physician, Harvard University who says the only way to have EBM is to have access to the "corporate hard drives" of the pharmaceutical industry. All the methodology and (anonymised) data.

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    2. John Holmes

      Agronomist - semi retired consultant

      In reply to John Holmes

      Opps: "reregistration data", not "regeneration data". My dyslexia strikes again.

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  6. Peter Wildblood

    logged in via email @gmail.com

    This was also a claim made on the Catalyst program in relation to statins: we will only really know what's going on when we have access to the hard drives of the big pharma.

    I agree and it's long overdue.

    Catalyst also raised the issue of the "ownership" of independent research by big pharma and there's the rub.

    A possible solution: Seek (not voluntarily) to have big pharma "donate" the cost of "medical representation" in all its forms to an independent authority tasked with (a) assessing…

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    1. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to Peter Wildblood

      The Cochrane Collaboration have sought to do something like this Peter - as a sort of one-stop shop for distilled evidenc-based medicine.

      But the Cochrane Collaboration realise that without access to Big Pharma's hard drives - they're working in the semi-dark. Hence Cochrane Collaboration are one of the prime supporters and initiators of the AllTrials Campaign.

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    1. Peter Parry

      Child and adolescent psychiatrist & senior lecturer at University of Queensland

      In reply to Michelle Bourke

      No Michelle, the European Medicines Agency http://www.ema.europa.eu/ema/ decided to release what drug trial data they have (still less than all the data the pharmaceutical companies have, but more than is published in the medical journals). The Australian govt has not said anything in this regard and nor to my knowledge yet has the Australian equivalent of the EMA - the TGA.

      The EMA has been stopped from releasing the drug trial data they have by legal action by two pharmaceutical companies. More pressure from the public and from medical and govt organisations is needed - hence the AllTrials campaign.

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    2. John Holmes

      Agronomist - semi retired consultant

      In reply to Peter Parry

      While we are at it, include the APVMA as well.

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  7. Baz B

    Writer/Researcher at Them

    Thanks for writing this. I started doing some research on this issue for a proposed article some while back and there was huge denialism, and I came cross many sources making sme fairly serious claims about the kind of information being with held andthe implications for public health. Nice work.

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