Monthly Archives: March 2012
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 Merck had data several years before Vioxx was withdrawn from the market that showed the drug increased the risk of heart attacks, but most of the data was unpublished and out of public view.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:
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.
Develop mechanisms for those who own trial data to share their raw data and individual patient data.
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.
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.
Identify, within all systematic reviews, trials that are not published, using sources such as clinicaltrials.gov and regulatory postings to determine what is missing.
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.
As discussed by Larry Husten on CardioBrief, a 2011 review article in Korean Circulation Journal appears to plagiarize from a 2009 article that was published in Journal of the American College of Cardiology. I spent several hours comparing the two articles, and found that several paragraphs in the KCJ article consisted primarily of paraphrasing, without attribution, of text from the JACC article. In addition, the majority of references in the KCJ article and two of the figures are the same as in the JACC article, and several of the headings are the same or very similar. The KCJ article does not cite the JACC article at all.
The JACC article is by Franz Messerli and Gurusher Panjrath. The KCJ article is by Chang Gyu Park and Ju Young Lee.
Moreover, Figure 4 in the KCJ article appears to have been copied from figure 1 in the 2009 revised European Guidelines on Hypertension Management, although the figure instead references a 2006 study by Messerli and colleagues that was published in the Annals of Internal Medicine.
See Larry’s post on CardioBrief for more details.
Update: Larry reports that the editor of KCJ contacted him to say that the article is now being investigated by the publishing committee of the Korean Society of Cardiology and that an additional investigation has been requested from the Ethics Commission of the Korean Association of Medical Journal Editors.