Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients by Ben Goldacre Page B

shortly see, and it often happens because people have found a drug to be unhelpful, or have had bad side effects. During these trials you’re measuring pain at regular intervals. But if some people drop out, you’re left with an important question: what kind of pain score should you use for them in your results? We know, after all, that people dropping out are more likely to have done badly on the drug.
    Pfizer decided to use a method called ‘Last Observation Carried Forward’, which means what you’d expect: you take the last measurement of pain severity while the patients were on the drug, from just before they dropped out, and then paste that in for all the remaining pain measures that they missed, after they stopped coming to follow-up appointments.
    The FDA disapproved of this: it pointed out, quite correctly, that Pfizer’s strategy would make the drug look better than it really is. For a fairer picture, we have to assume that the dropouts stopped taking the drug because of side effects, so their pain score should reflect the reality, which is that they would never get any benefit from the drug in normal use. The correct level of pain to record for them is, therefore, their pain at the beginning of the study, before they had any kind of treatment (if you’re interested, this is called ‘Baseline Observation Carried Forward’). The analysis was duly redone, properly, and a more modest, more accurate view of the benefits of the drug was produced. In this case, it turns out that using the ‘last observation’ method overestimated the improvement in pain by about a quarter.
    Here’s the catch. Four out of five of these trials were then published in the peer-reviewed academic literature, the place where doctors look for evidence on whether a drug works or not (one trial wasn’t published at all). Every single one of the published analyses used ‘Last Observation Carried Forward’, the dodgy method, the one that exaggerates the benefits of the drug. Not one of them acknowledges that ‘last observation’ is a technique that overstates these benefits.
    You can see why it is important that we have access to all the information we can possibly get on every drug trial: not only are some whole trials withheld from us, but there are often hidden flaws in the methods used. The devil is in the detail, and there are many dodgy trials, as we shall soon see, with flaws that may not be clear even in the academic papers, let alone in the thin and uninformative summaries from regulators. Furthermore, as we shall also see very shortly, there are often worrying discrepancies between the regulators’ summary documents and what actually happened in the trial.
    This is why we need to get hold of a more detailed document on each trial: something called the Clinical Study Report (CSR). These are long pieces of work, sometimes thousands of pages, but they are complete enough for the reader to reconstruct exactly what happened to all the participants; and they will let you find out where the bodies are buried. Drug companies give this study report to the regulator – though still only for formally licensed uses of the drug – so both have a copy, and both should be happy to hand it over.
    We will now see what happens when you ask them.
    Three: Regulators withhold study
reports that they do have
    In 2007, researchers from the Nordic Cochrane Centre were working on a systematic review for two widely used diet drugs, orlistat and rimonabant. A systematic review, as you know, is the gold-standard summary of the evidence on whether a treatment is effective. These are life-saving, because they give us the best possible understanding of the true effects of a treatment, including its side effects. But doing this requires access to all of the evidence: if some is missing, especially if unflattering data is deliberately harder to obtain, we will be left with a distorted picture.
    The researchers knew that the trial data they were able to