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BMJ editor: Open letter to Roche about oseltamivir trial data

In BMJ:

Roche promised in 2009 to release full reports from clinical trials of oseltamivir in response to an investigation by the BMJ and the Cochrane Collaboration.  In this open letter to John Bell, regius professor of medicine at Oxford University and a Roche board member, the BMJ’s editor in chief further urges the company to disclose the full data.

Read the full letter here.

Background here.

Ben Goldacre on missing data and publication bias

Ben Goldacre at Strata Conference

Here is a video of Ben Goldacre speaking at the Strata Conference in London earlier this month (H/T Chris Southan).

I also recommend his book, Bad Pharma:  How drug companies mislead doctors and harm patients, which goes into detail on how missing data and publication bias distort the medical literature and harm patients.

 

Data sharing as a moral imperative

In the USA at least, the data legally belong to trialists on the grounds that it requires work to create knowledge from data. But science, particularly medical science, is essentially an enterprise conducted for moral reasons. We need to do not just what is legal but what is right. As such, we must take into account the probable wishes of the patients who give us their blood, fill in our questionnaires and die on our trials. It is difficult to believe that any patient on my trial, who completed complex questionnaires so diligently over such a long period of time, would really have wanted me to keep the data for myself rather than share it with others for the benefit of medical science in general.  Vickers AJ.  Whose data set is it anyway?  Sharing raw data from randomized trials.  Trials.  2006;7:15.

Every day, patients and their caregivers are faced with difficult decisions about treatment. They turn to physicians and other healthcare professionals to interpret the medical evidence and assist them in making individualized decisions.  Unfortunately, we are learning that what is published in the medical literature represents only a portion of the evidence that is relevant to the risks and benefits of available treatments. In a profession that seeks to rely on evidence, it is ironic that we tolerate a system that enables evidence to be outside of public view.  Krumholz HM. Open Science and Data Sharing in Clinical Research: Basing Informed Decisions on the Totality of the Evidence. Circulation: Cardiovascular Quality and Outcomes. 2012;5: 141-142

We are all patients, and will all face questions about what medical treatments to pursue.  Some questions are trivial and unimportant, others can mean the difference between life and death.  We rely on evidence-based medicine to give us reliable information about the risks and benefits associated with medical interventions, but a disturbing amount of evidence indicates that the medical literature is not always reliable.  Many clinical trials are not published within a reasonable time after completion or are never published at all.  Missing data leads to systematic reviews that are based on only a portion of the trials that were conducted, which can affect the results in unknown and unpredictable ways.  Missing data may in some cases hold important information about risk, as in the case of Vioxx (rofecoxib).  Merck had data several years before Vioxx was withdrawn from the market that showed the drug increased the risk of heart attacks, but most of the data was unpublished and out of public view.  In other cases, clinical trials are published but the data are reported in a misleading and biased way, as when a negative trial is presented so as to appear positive, or analyses showing harm are omitted.

What is to be done?  What can we do to make evidence-based medicine more evidence-based?  Four commentaries in the March 2012 issue of Circulation:  Cardiovascular Quality and Outcomes discuss how making clinical research data available outside individual drug and device companies or research groups could greatly add to the depth and reliability of our knowledge.  Currently, with certain exceptions, access to most clinical trial data is restricted to the investigators or the funders.  Harlan Krumholz, in an editor’s perspective, outlines the key concepts:

Now is the time to bring data sharing and open science into the mainstream of clinical research, particularly with respect to trials that contain information about the risks and benefits of treatments in current use. This could be accomplished through the following steps:

    1. Post, in the public domain, the study protocol for each published trial. The protocol should be comprehensive and include policies and procedures relevant to actions taken in the trial.

    2. Develop mechanisms for those who own trial data to share their raw data and individual patient data.

    3. Encourage industry to commit to place all its clinical research data relevant to approved products in the public domain. This action would acknowledge that the privilege of selling products is accompanied by a responsibility to share all the clinical research data relevant to the products’ benefits and harms.

    4. Develop a culture within academics that values data sharing and open science. After a period in which the original investigators can complete their funded studies, the data should be de-identified and made available for investigators globally.

    5. Identify, within all systematic reviews, trials that are not published, using sources such as clinicaltrials.gov and regulatory postings to determine what is missing.

    6. Share data.

It must be acknowledged that there are many obstacles — political, cultural, financial — to accomplishing these goals.  Some of these obstacles are discussed in the other three commentaries, which are open access and which I urge you to read:

Spertus, JA.  The Double-Edged Sword of Open Access to Research Data.  Circulation:  Cardiovascular Quality and Outcomes.  2012;5;143-144.

Ross JS, Lehman R, Gross CP.  The Importance of Clinical Trial Data Sharing:  Toward More Open Science.  Circulation:  Cardiovascular Quality and Outcomes.  2012;5;238-240.

Gotzsche PC.  Strengthening and Opening Up Health Research by Sharing Our Raw Data.  Circulation:  Cardiovascular Quality and Outcomes.  2012;5;236-237.

Whatever the difficulties, the current situation is clearly intolerable.  Patients deserve reliable information on the risks and benefits of medical treatments and the subjects of clinical trials deserve that their contributions be fully used to benefit other patients.

Addendum March 26, 2012:  Please also see these posts by Jim Murray and Gary Schwitzer.

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