1.1 Why treatment uncertainties should be addressed

Ignoring uncertainties about the effects of treatments has led to avoidable suffering and deaths. To reduce this suffering and premature mortality, treatment uncertainties must be acknowledged and addressed, first by reviewing systematically what is already known, and then in well-designed research to reduce continuing uncertainties.

Trying to do more good than harm

Why do we need fair tests of treatments in health care? Have not doctors, for centuries, ‘done their best’ for their patients? Sadly, there are many examples of doctors and other health professionals harming their patients because decisions were not informed by what we consider now to be reliable evidence about the effects of treatments. With hindsight, health professionals in most if not all spheres of health care have harmed their patients inadvertently, sometimes on a very wide scale (Silverman 2003Grimes 2007). Indeed, patients themselves have sometimes harmed other patients when, on the basis of untested theories and limited personal experiences, they have encouraged the use of treatments that have turned out to be harmful. The question is not whether we must blame these people, but whether the harmful effects of inadequately tested treatments can be reduced. They can – to a great extent.

A first step is acknowledging that treatments can sometimes do more harm than good (Gregory 1772; Haygarth 1800; Fordyce 1802; Behring 1893). We need to be more willing to admit uncertainties about treatment effects, and to promote tests of treatments to adequately reduce uncertainties.
We refer to such tests as ‘fair tests’.

Why theories about the effects of treatments must be tested in practice

Van Helmont 1662People have often been harmed because treatments have been based only on theories about how health problems should be treated, without testing how the theories played out in practice. For example, for centuries people believed the theory that illnesses were caused by ‘humoral imbalances’. As a result, patients were bled and purged, made to vomit and take snuff, all in the belief that this would end the supposed imbalances. Still, a 17th century Flemish doctor, Johannes van Helmont, was impertinent enough to challenge the medical authorities of the time to assess the validity of their theories by proposing a fair test of the results of their unpleasant treatments (Van Helmont 1648).

PortraitBy the end of the 18th century, British army and naval surgeons had begun to show the harmful effects of bloodletting for treating “fevers” (Robertson 1804; Lesassier Hamilton 1816). A few decades later, the practice was also challenged by a Parisian physician (Louis 1835). Yet at the beginning of the 20th century, mainstream doctors in Boston, USA, who were not using bloodletting to treat pneumonia were still being judged negligent (Silverman 1980). Indeed, Sir William Osler, one of the most influential medical authorities in the world, who was generally cautious about recommending unproven treatments, advised his readers at the end of the 19th century that: “during the last decades we have certainly bled too little. Pneumonia is one of the diseases in which a timely venesection [bleeding] may save life. To be of service it should be done early. In a full-blooded, healthy man with a high fever and bounding pulse the abstraction of from twenty to thirty ounces of blood is in every way beneficial” (Osler 1892).

Benjamin SPockAlthough the need to test the validity of theories in practice was recognized by Islamic physicians at least a millennium ago (Ibn Hindu 10th-11th century), this important principle is still too often ignored. For instance, based on untested theory, Benjamin Spock, the influential American child health expert, informed the readers of his bestselling book ‘Baby and Child Care’ that a disadvantage of babies sleeping on their backs was that, if they vomited, they would be more likely to choke. Dr Spock therefore advised his millions of readers to encourage babies to sleep on their tummies (Spock 1966). We now know that this advice, apparently rational in theory, led to the cot (crib) deaths of tens of thousands of infants (Gilbert et al. 2005).

Deadly MedicineAnother dramatic example of the dangers of applying untested theory in practice was found in the use of drugs to prevent heart rhythm abnormalities in people having heart attacks. Because heart rhythm abnormalities are associated with an increased risk of early death after heart attack, the theory was that drugs that reduced these abnormalities would also reduce early deaths. Just because a theory seems reasonable doesn’t prove that it is necessarily right when applied in practice. Years after the drugs had been licensed, it was discovered that they actually increase the risk of sudden death after heart attack in these patients. Indeed, it has been estimated that, at the peak of their use in the late 1980s, they may have been killing as many as 70,000 people every year in the United States alone (Moore 1995) – many more than the total number of Americans who died in the Vietnam War.

Animal ResearchMisplaced confidence in theoretical thinking has also resulted in some treatments being rejected inappropriately because researchers did not believe that they could work. Theories based on the results of animal research, for example, sometimes correctly predict the results of treatment tests in humans, but this is not always the case (Perel et al. 2007). Based on the results of experiments in rats, some researchers became convinced that there was no point in giving clot-dissolving drugs to patients who had experienced heart attacks more than six hours previously. Had no such patients participated in some of the fair tests of these drugs we would not know that they can benefit from this treatment (Fibrinolytic Therapy Trialists’ Collaborative Group 1994).

Observations in clinical practice or in laboratory and animal research may suggest that particular treatments will or will not benefit patients; but as these and many other examples make clear, it is essential to use fair tests to find out whether, in practice, these treatments do more good than harm, or vice versa.

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