{"id":63055,"date":"2016-01-08T23:30:32","date_gmt":"2016-01-09T04:30:32","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=63055"},"modified":"2016-01-09T13:53:32","modified_gmt":"2016-01-09T18:53:32","slug":"john-henrys-hammer-an-interim-summary","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/01\/08\/john-henrys-hammer-an-interim-summary\/","title":{"rendered":"john henry’s hammer: an interim summary…"},"content":{"rendered":"\n
In a way, what I’m trying to do here is at cross purposes with some of my own beliefs. Short term Randomized Clinical Trials [RCTs] can tell us whether a drug has the desired medicinal properties; something about the strength of those properties; the incidence of early adverse effects; and can identify some but certainly not all serious toxicity. Long term trials, the experience of practicing clinicians, and the reports of patients taking these drugs are a much more important source of ongoing information. Our system of drug development and patenting has created a situation where the early clinical trials are way overvalued during the in-patent period [even the "good ones"], and often the medication harms are suppressed until they emerge in legal actions late in the day – after the damage has already been done. In addition, the early RCTs are industry productions, and many of them have made mincemeat of the scientific method they’re meant to represent.  So I’m focusing on the efficacy testing of short term RCTs when we all know that the most important thing is the long term harms. But I base that approach on the medical principles of preventive medicine, specifically secondary prevention – early detection and rapid intervention. I know that the ultimate answer is Data Transparency and Independent Trial Analysis, but until that happens, educating as many people as possible about how to evaluate these early trials seems an essential way to intervene in the present…<\/font><\/sup><\/em><\/div>\n

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The a priori<\/em> Protocol<\/font><\/strong><\/u>:<\/div>\n
A randomized, placebo controlled, double-blinded clinical trial [RCT<\/font> for short] is not exploratory research. It’s more in the range of product testing. And its validity rests on a formal declaration of the details of how the study will be conducted and specifically what measurements will be taken, what will be the primary [and secondary] outcome variables, and how the data will be analyzed. The phrase a priori<\/font><\/em> means before the study begins<\/font><\/em>. We can never count on the sanctity of the blinding. People peek. But we can trust a formal Protocol filed before the study starts. So step one in evaluating a study is to get the Protocol, or as close to the Protocol as possible. That information should be in the article, but if it’s unclear, you can often get at it from the information on clinicaltrials.gov<\/a>. I’ve yet to see a study where the Protocol was changed in midstream that didn’t smell like three day old fish. Likewise, if you can’t figure out what the Primary and Secondary Outcome Variables are, be suspicious of the whole enterprise.<\/div>\n

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Continuous Variables:<\/a><\/div>\n
Since we don’t have the luxury of seeing the raw data, we have to rely on Summary Data<\/font>. In the case of Continuous Variables, that includes the MEAN<\/font>, either the Standard Deviation<\/font> or the Standard Error of the Mean<\/font>, and the Number<\/font> of subjects [μ<\/font><\/strong>, σ <\/font><\/strong>or sem<\/font><\/strong>, and n<\/font><\/strong>]. In groups of sufficient size [>30], those three parameters are a reasonable proxy for the datasets. If the Summary Data<\/font> is provided in the article, the task of quickly vetting a Continuous Variables<\/font> is straightforward. Again, if you can’t figure out what the Summary Data <\/font>is, be suspicious of the whole enterprise:<\/div>\n