Clinical trials are supposed to generate reliable data to support healthcare decisions and policies at several levels. Regulators use the data to control the marketing and use of medicines and healthcare products. Clinical practice guidelines are produced by healthcare organizations (from the WHO downwards) as well as professional bodies. Clinicians apply and interpret these guidelines for individual patients, as well as prescribing medicines, products and procedures, both on-label and off-label.
Given the importance of these decisions and policies for patients, there are some critical issues concerning the quality of clinical trial data, and the ability of clinicians, researchers, regulators and others to make sense of these data. Obviously there are significant commercial interests involved, and some players may be motivated to be selective about the publication of trial data. Hence the AllTrials campaign for clinical trial transparency.
But there is a more subtle issue, to do with the way the data are collected, coded and reported. The BBC has recently uncovered an example that is both fascinating and troubling. It concerns a clinical trial comparing the use of stents with heart bypass surgery. The trial was carried out in 2016, funded by a major manufacturer of stents, and published in a prestigious medical journal. According to the article, the two alternatives were equally effective in protecting against future heart attacks.
But this is where the controversy begins. Researchers disagree about the best way of measuring heart attacks, and the authors of the article used a particular definition. Other researchers prefer the so-called Universal Definition, or more precisely the Fourth Universal Definition (there having been three previous attempts). Some experts believe that if you use the Universal Definition instead of the definition used in the article, the results are much more one-sided: stents may be the right solution for many patients, but are not always as good as surgery.
Different professional bodies interpret matters differently. The European Association for Cardio-thoracic Surgery (EACTS) told the BBC that this raised serious concerns about the current guidelines based on the 2016 trial, while the European Society of Cardiology stands by these guidelines. The BBC also notes the potential conflicts of interests of researchers, many of whom had declared financial relationships with stent manufacturers.
I want to draw a more general lesson from this story, which is about the much-vaunted Single Version of Truth (SVOT). By limiting the clinical trial data to a single definition of heart attack, some of the richness and complexity of the data are lost or obscured. For some purposes at least, it would seem appropriate to make multiple versions of the truth available, so that they can be properly analysed and interpreted. SVOT not always a good thing, then.
See my previous blogposts on Single Source of Truth.
Deborah Cohen and Ed Brown, Surgeons withdraw support for heart disease advice (BBC Newsnight, 9 December 2019) See also https://www.youtube.com/watch?v=_vGfJKMbpp8
Debabrata Mukherjee, Fourth Universal Definition of Myocardial Infarction (American College of Cardiology, 25 Aug 2018)
See also Off-Label (March 2005), Is there a Single Version of Truth about Statins? (April 2019), Ethics of Transparency and Concealment (October 2019)