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Category: EBM

Why Cochrane is Wrong About Hypertension. Very Wrong.

By SWAPNIL HIREMATH, MD

Archie Cochrane and the Cochrane Collaboration

Archie Cochrane was born in Scotland, educated in London (King’s College, University College and London School of Hygiene and Tropical Medicine) and worked in Cardiff, Wales. His work as a doctor during the Spanish Civil War and World War II, especially in a prisoner of war camp in Salonica, is credited with his push towards generating higher quality evidence. In his description of the clinical trial he conducted, he mentions James Lind as his hero. Ironically, that clinical trial – with weak randomization, open allocation, non-blinding of investigator or participants, and use of surrogate outcomes, would rate poorly in the Cochrane risk of bias tool.

But the scientific method of measuring stuck with him, and among many other achievements, he did perform a proper randomized clinical trial (RCT) a few decades later. He continued to be a strong supporter of RCTs and pushed for the Medical Research Council (MRC) to move from purely fundamental research towards applied clinical research. As an aside, the first proper RCT in the modern era was funded by the MRC and was published in 1950 – on the use of Streptomycin vs para-aminosalicylic acid, or a combination, in tuberculosis. Far more influential was his paper (and later book) published as part of the Rock Carling Fellowship, available here freely and worth a read. It’s where he puts forward the vision for RCTs in moving towards what he termed an ‘effective, efficient health service’.

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Surrogate End Points Ain’t all that Bad

By CHADI NABHAN MD MBA

Dr. Chadi Nabhan, MD, MBA

Life is busy, yet we somehow find time to stay engaged on social media, remain engrossed in the 24/7 news cycle, and continue our futile efforts to resist clickbait. While social media can allow us to mindlessly scroll through feeds, it also provides an avenue to provoke vigorous dialogue, however diverse, controversial, or even rooted in unfettered biases. These exchanges have served as the primordial soup for a virtual friend or foe-ships. Tense and argumentative Twitter exchanges are especially entertaining given the challenges in justifying a position in fewer than 280 characters. Thus, tweetorials have emerged to explain a point of view via a thread of comments since it is not always easy to do so in 1 or 2 tweets. The longer the tweetorial, the more heated the debate. What I am trying to get at here, somewhat obtusely, is the concept of surrogates.

I have already suggested a surrogate. Length of a tweetorial is a surrogate for degree of controversy of the topic. Meaning, length is a surrogate, a proxy. We are surrounded by surrogates. Longer wait lines at restaurants and bars imply a hipper joint or tastier menu. My child being extra nice to me is a surrogate for him wanting more time on electronics. Not a day goes by without folks arguing about surrogate endpoints. I wanted to dig deeper into surrogates and since I am a physician, I’m focusing on surrogates in medicine. Apologies to those who thought I would be discussing restaurants or exotic trips.

I want to make sure my definition of surrogates is accurate: Merriam-Webster dictionary for enlightenment. The first use of the word “surrogate” was in 1533, B.T. (“Before Twitter”). A surrogate is defined as “one appointed to act in place of another” or “one that serves as a substitute”. We use surrogate endpoints in clinical trials as a substitute for other end points.

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