evidence in this, and Gina Fromm’s subsequent case, made it clear that in addition to doubling rates of congenital malformations it doubles the rate of miscarriages and increases voluntary terminations of pregnancy.
Yet extraordinarily in the face of this evidence not only doctors but even ethicists line up to say antidepressants are being underused in pregnancy.37 There is a suspension of common sense here that has been brought about by company marketing of controlled trials and evidence based medicine. Ironically a requirement for controlled trials was built into Senator Kefauver’s 1962 amendments as this seemed a method to limit rather than promote treatments, but these trials have in fact become the primary marketing tool of pharmaceutical companies. The marketers have selected the trials that suit, had them polished by ghostwriters just as much as a political speech might be, before smuggling them past the peer review systems of academic journals and meetings. But none of this would have the power to influence doctors had the very meaning of clinical trials not been turned inside out.
3
Follow the Evidence
When a journalist jumps out from behind a hedge on the eleventh hole of a Caribbean golf course to ambush a professor of medicine from one distinguished university and a professor of psychiatry from another after both gave brief lectures that morning, and he asks the men whether their company-sponsored trip would influence their judgment, the response will be “Of course not!” If asked what does influence them, these academics will confidently point to the published evidence. They follow the evidence, not the money. Even if a doctor is pocketing the lecture fee rather than putting it into a research fund, the answer will still be the same.
There is a rich literature on how even minor gifts can hugely influence the recipient,1 and an equally rich literature on how doctors, when asked, readily agree that their colleagues are swayed by favors while still denying that they themselves can be influenced.2 That gifts can corrupt seems so obvious to everyone except doctors that in 2009 a Sunshine Act was introduced in the US Senate to mandate disclosure by pharmaceutical companies of money or other gifts given to doctors or medical academics.3
The response from the medical community to moves like the Senate's bill that seem to impugn medical professionalism is bewilderment. While traditionally doctors have put great store in professionalism, at least as important in their response to this issue is their belief that scientific research is immune to gifts, biases, or conflicts of interest. It's taken for granted that data don't lie, and this leaves medical personnel and their academic colleagues sanguine about gifts, from pens to all-expenses- paid conferences in the Caribbean. If anyone in the media can point to a mismatch between what doctors on the golf course prescribe in their practice and the published evidence, that would be another matter—but until Birnam Wood comes to Dunsinane there is no reason for concern.
These days, almost as though Macbeth's witches had invested in the fixedness of Birnam Wood, pharmaceutical companies also take their stand on the published evidence. From senior executives mingling with medical academics to drug reps visiting medical trainees, company personnel tout the virtues of controlled trials and exhort doctors to practice evidence-based medicine at every turn.
In its first manifestations, controlled trials and evidence-based medicine were known for demonstrating that fashionable treatments did not work. If now pharmaceutical companies invoke what they call evidence- based medicine to justify the status quo, that should at least raise some suspicion about what might be going on. In chapter 4 and 5 we will look at how companies cherry-pick the trial data that suits them, leaving inconvenient data unpublished and making a mockery of science. But in this chapter the focus is on how they have managed to turn controlled trials inside out, neutering their potential to show that some currently fashionable drugs don't work and transforming them into a means to sell worthless remedies.
THE TURN TO NUMBERS
Insofar as the Hippocratic dictum of “first do no harm” appears a good idea, we should adopt the view that we know very little. But faced with real diseases from Alzheimer's dementia to malignant cancers to rheumatoid arthritis, when both those affected and their doctors become desperate and vulnerable, remaining calm and skeptical is easier said than done. This is precisely why we need to pin down how much we do know about medical treatments, and for this purpose controlled trials can be a godsend.
There are many situations where it is not difficult to know when a drug or a medical procedure works. In the case of alcohol, for instance, we comfortably base our judgments on the fact that we can see certain effects occur reliably soon after intake of the drug, with some relationship between how much we imbibe and the effects we experience. We know about the analgesic effect of opium and the sedative effects of the barbiturates in the same way as we know about alcohol and about the benefits of having a dislocated shoulder popped back into place or a kidney stone removed, from the immediate relief.
Not all treatments have effects that are this clear-cut, though, nor are all the effects even of alcohol or sedatives self-evident. While a sedative may be usefully sedating and in this sense work, it still may not be all that useful in the long run for nervous conditions. Even bigger problems arise when the beneficial effects of a treatment are less immediate than those of alcohol or opiates, or when there are substantial differences in the effect of a treatment from one person to the next, or when the natural history of a condition is such that some people would have recovered anyway. In these cases, treatments may appear to be linked to cures and doctors or patients, who understandably want to see a treatment working, may jump to the conclusion that the treatment has worked when in fact it hasn't. This is a gap that quacks and charlatans exploit. In a world where nothing much worked, the charlatan engendered many false hopes. In today's world, where getting the wrong prescription may mean you needlessly suffer harmful side effects or miss out on a treatment that really would have helped, the consequences may be more serious.
In these more ambiguous cases—of which there are many in medicine—how do you know whether or not a treatment is likely to have any benefits and what hazards it may entail? For several centuries at least some physicians appreciated that before a proposed new remedy could be accepted, its effects would need to be observed under controlled conditions. There would need to be some way to demonstrate that any improvement in patients was due to the remedy, and not to some other factor, or even to chance. Some group of patients living under similar conditions that could be divided into comparable groups, only some of which were given the remedy, would be needed. But short of imprisonment or quarantine, this is not easily done.
In 1747, James Lind, the Scottish physician who served as ship's doctor on the South Seas-bound Salisbury, was given the perfect opportunity. Some of the sailors developed scurvy, a fearsome disease that caused tissue breakdown—wounds failed to heal, teeth fell out, and victims began to bleed into their skin or from their bowels. In some long-distance sea voyages up to half a ship's crew might die from it. Faced with twelve sailors whose “cases were as similar as I could have them” and who were all on the same diet, Lind was able to give two of the men cider, two vitriol, two vinegar, two sea-water, two oranges and lemons, and two a mix of nutmeg, garlic, mustard seed, and balsam of Peru. Those given the oranges and lemons improved rapidly, the others languished.4 Even though there was limited scope for any other explanation of these recoveries, many attributed the improvement to ventilation (although that was the same for all twelve patients), while even Lind himself was slow to credit the citrus fruits for the favorable response. It took the British navy another fifty years to include lime juice in the provisions for a voyage, after which British sailors were widely termed limeys. In this case, when faced with a choice between their expectations and the evidence, observers at first clung to their expectations—a pattern we shall see again and again.
On a much grander scale, but in a less controlled fashion,
