Of Trials and Guidelines: How Sturdy Are Medicine’s Foundations?

by admin on October 31, 2011

DrSamGirgis.com has the pleasure of hosting the following post by guest blogger, Dr. Richard Andraws MD, who is a Board Certified Cardiologist


A wise man proportions his belief to the evidence.

–David Hume

Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.

—Sackett DL, et al. BMJ 1996; 312: 71.

The concept of evidence based medicine (EBM) dates back to the ancient Greeks, but it took hold in the 1990s among contemporary clinicians. EBM makes sense when you think about it. It tells doctors that the best way to treat their patients is to combine their experience and expertise with data from rigorously executed clinical trials. These are often randomized controlled trials in which statistically identical groups of patients are treated either with a new therapy or a standard therapy or placebo. Outcomes are then compared. If conducted appropriately, this type of trial is the most powerful scientific tool we have in medicine. It tells us whether we’ve struck gold or squirted lemon juice in our eye.

The problem is that there is too much evidence. No doctor can possibly assimilate all the research on a disease and then integrate that into patient care. Because of this, the government and professional societies periodically release guidelines, or expert summaries of the evidence followed by recommendations. Ultimately, these guidelines are what drive day-to-day practice (and increasingly how doctors get paid for what they do). Problem solved—right?

Not quite. Important trials are so large and expensive that only the government or major pharmaceutical and medical device companies have the resources to fund and coordinate them. In the latter case, there is a vested interest: if a company’s product shows effectiveness, an investment of millions will reap billions in revenue. But are those ballyhooed “positive” trials as wonderful and perfect as they seem to be? Moreover, companies typically fund and promote their research through physician experts who receive research grants as well as honoraria. This is logical and very reasonable: investors want the most respected thought leaders overseeing their trials and spreading the word to other clinicians. What happens when these same leaders are tapped (as is often the case) for a guideline writing committee?

Two recent articles scrutinize these complexities. The first, by Neuman and colleagues in British Medical Journal, examines the prevalence of conflicts of interest among guideline writers in the United States and Canada. The investigators analyzed a total of 14 guidelines–written by governmental and professional society panels–that address the management of diabetes and high cholesterol. They found that 52% of writers had received grants, honoraria or held stock in device and pharmaceutical firms. Canada had more experts with conflicts than the US (83% vs. 58%). Governmental guideline writers had fewer conflicts than those writing for societies (16% vs. 69%.) The study cannot tell us whether having a financial conflict of interest caused expert bias, but the implication is that it very well could have. Thus, a critical pillar of modern medical care may be compromised. The authors call for enforcement of an Institute of Medicine recommendation that guideline panels be conflict-free.

The second, an editorial by Krumholz and Ross in the Journal of the American Medical Association, addresses a major flaw of clinical trials: what happens to the data? Currently, limited summary data (mostly the positive and impressive) are presented at meetings and in major medical journals. However, “patient level” data, (that is, the wealth of information collected on each individual subject) are typically not available to the public or even to other researchers. Such data often hold key insights into such things as drug and device safety. The authors present a model for intelligent transparency that balances the concerns of industry with the need for reform. Study sponsors would allow academic institutions, in association with conflict-free panels, access to all trial data. The panels would vet the study by independently reanalyzing the data and confirming the findings. Other investigators would also have access to the data for their own research. The whole thing would be supervised by multidisciplinary steering committees that include physicians, patients and policy makers. The authors hope their proposal would strengthen findings, remove doubt as to whether data were manipulated, and increase patient safety. And they reveal that the first test of their proposed model is currently underway.

By raising awareness of conflicts of interest and proposing innovative solutions, the authors of both papers are agreed: it behooves all wise and compassionate clinicians to proportion the care they deliver to the best evidence available.



Neuman J, Korenstein D, Ross JS, et al. Prevalence of financial conflicts of interest among panel members producing clinical practice guidelines in Canada and the United States: cross sectional study. BMJ 2011; 343:d5621

Krumholz HM, Ross JS. A model for dissemination and independent analysis of industry data. JAMA 2011; 306: 1593-94.

Related Posts Plugin for WordPress, Blogger...

{ 0 comments… add one now }

Leave a Comment