The Placebo Effect

What is the "placebo effect"? The words are bandied around constantly but tend to be poorly understood. Put simply, the "placebo effect" is the medical response of your body to the idea that you are taking drugs, in the absence of actual drugs. How can this occur? There is nothing mystical about this, the effect of mood on brain chemistry is well documented, and the physiological effects of brain chemistry on our body are surprisingly strong. What is more unusual is a question posed by a recent article in Wired - why does the placebo effect appear to be getting stronger in drug trials?

Is this true? Is the placebo effect actually getting stronger? Actually we have no idea. Drug companies never test the strength of the placebo effect. To actually test the placebo effect you need to have three groups: no treatment, placebo treatment and drug treatment. The "no treatment" group measures the spontaneous remission rate (is, the background of how many people would get better over the treated period of time without treatment). The "placebo treatment" group can then measure any additional effects of the patients thinking they are taking drugs, while the "drug treatment" group measures the biomedical effect of the drug. Since drug companies almost never include a "no treatment" group, the increasing effect in the "placebo treatment" group could either be due to increasing spontaneous remission rates or due to an increasing effect of placebos. Changes in spontaneous remission rate are just as feasible as changes in the placebo effect, as the health of the population is generally increasing over time, and a generally healthy person has a higher spontaneous remission rate.

If we assume, however, that it is the placebo effect that is increasing over time, do we have reasonable explanation for this? The answer is probably a lot more simple than drug companies are making it out to be. Changes in the scale of the placebo effect are regionally localised and concentrated in conditions such as depression, epilepsy and pain. The simplest explanation (and hence, according to Occam's razor, the one we turn to first) is that the patient composition of these groups has been changing over time, especially in certain regions. In particular, we have observed large improvements in medical diagnosis, such that more subtle cases are being detected. We have also experienced a "medicalisation" of non-medical conditions, strong moods or emotions being labelled as medical conditions and lumped together with cases caused by biomedical disruptions (ironically driven largely by drug companies seeking to expand their markets). It would be predicted that less severe cases of medical conditions, and emotional/behavioural conditions misdiagnosed as medical conditions, would be more amenable to the effects of placebos on brain chemistry. A simple test for this hypothesis exists - take an existing drug and recruit a patient cohort using identical criteria as the original drug trial. If the "altered patient cohort" hypothesis is correct a new drug trial using past inclusion criteria should show the same level of placebo effect as the original trial.

Of course the real issue for the drug companies is that the drugs being developed and tested are less and less efficacious. The placebo effect is only an issue when drugs have borderline effects. If a drug company invented a new quinine or penicillin there would be no concerns about skating around the edges of statistical significance.

A Self-correcting System

The ability of science as a method to understand reality is demonstrated by the countless successes science has had in developing technology. Antibiotics, vaccination, flight, agriculture, all of these advances clearly work. Why is this? People came up with many ideas to prevent smallpox in the past, but they consistently failed. The development of a smallpox vaccine which actually worked does not demonstrate that scientists have any unique intelligence, but rather it is testimony to the power of a self-correcting system.

Hypotheses are worthless if they are not tested and then discarded if they fail testing. The process of science is not just coming up with an idea of how to cure smallpox, many people clung to their ideas of what would cure smallpox even as they died. Rather, science is testing this idea by looking at the evidence. Uniquely, science discards ideas that just don't work. The simple process of keeping ideas that work and discarding ideas that don't work has built an amazing edifice of knowledge.

The real beauty of the scientific method is that it does not depend on any single person being right or wrong, being ethical or unethical. There will always be scientists who lie or cheat, falsify data or hide experiments that disprove their pet theory. But the hypotheses that these people put forward will always be discarded, because they will fail tests by other scientists.

Best of all, scientists have a vested interest in knocking down incorrect theories. Often you will hear from anti-science campaigners that scientists are hiding data that the theory of [evolution] / [global warming] / [insert hated theory here] is incorrect. They believe in a vast conspiracy of scientists each trying to hold up a false theory for some unexplained nefarious purpose, assuming that scientists don't want to prove a theory incorrect. They fundamentally do not understand the system of science.  Personal glory does not come to the scientists who prove yet again that the theory of gravity works, personal glory comes to the scientist who finds an exception, who proves a theory incomplete, who can unravel the fatal flaw in a centuries old dogma! Einstein, Newton, Copernicus, Darwin, these are all scientists who destroyed the prevailing theories of their age. Every scientist today would love to join their glorious ranks.

A scientist who could prove today that the theory of relativity, evolution or global warming was wrong would publish in the highest journals, win the Nobel Prize, earn household recognition and become rich. There are only two ways a theory such as evolution could still stand today:

1) Every scientist working in the field is deliberately concealing data that disproves evolution, despite knowing that breaking the nefarious conspiracy would earn them recognition as a leader of science, a place in the history books and a lot of personal glory;
or
2) There are no experiments that reveal a fatal flaw.

That is the beauty of science, individuals have huge power to make advances but very little ability to make delays, since theories are judged by experimental results. To reject science you have to reject human nature and believe in an alternative reality where everyone acts uniformly against their personal interests. Trust in science is not trust is individual scientists, it is trust in a system that for thousands of years has produced results, a system that is self-correcting, a system that acts as an 'invisible hand' to select only the models of reality that actually work, regardless of whether the individuals involved were motivated by a selfless search for truth or a greedy struggle for personal glory. The scientific method is an emergent phenomenon which self-corrects the activities of individual scientists to develop only the most robust theories that have so far resisted every attempt to knock them down.