We really didn’t need
another study
into the Placebo Effect,
but it
made the researchers
feel better
Nico Reznick
Years ago I saw a cartoon that showed two orderlies transferring a dead patient’s body to the hospital morgue. One orderly asks the other, “What did he die from?” The second orderly replies, “Poor guy, he died from an overdose of placebos.”
Placebos obviously don’t kill. However, placebo-phobia does. As the deadly COVID-19 pandemic sweeps indiscriminately across the world, hundreds of thousands of patients are dying needlessly. So, who is afraid of the placebo effect? The answer is physicians. I will explain.
Until the 1960s, drugs had only to pass safety tests before being allowed for marketing. The Thalidomide tragedy was a turning point for the regulation of drug development in the United States. In 1962, legislators tightened restrictions around the approval process for drugs being marketed and sold in the US with the Kefauver-Harris Drug Amendments Act.
Dr. Louis Lasagna, a renowned researcher and clinical pharmacologist at Johns Hopkins University, was a proponent of stricter rules for drug approvals. As an investigator of the placebo effect, Dr. Lasagna maintained that the experience of patients and physicians was an unreliable basis for drug approvals. Why? Because the benefit observed may be due to the “placebo effect”.
Dr. Lasagna’s testimony led to changes in the drug review process and the introduction of the “gold-standard”, a rigorous standard of testing that typically requires the participation of between hundreds and thousands of suitable patients in at least two randomized and well-controlled studies.
Over time, the gold-standard has become more complex, and more costly. The price of satisfying the gold-standard rose to an astounding average of $1.7 billion per drug in 2004, meaning that only drugs with enormous sales and profit potential are selected for development. Drugs that are unpatentable, or generics (off-patent), rarely stand a chance of finding an investor and making it to market or registering a new use.
With the arrival of COVID-19, the worst evils of the gold-standard of drug approval have become patently clear. A long list of safe, affordable drugs, with solid scientific rationale against COVID-19, are being denied from hundreds of thousands of patients whose lives can potentially be saved, today.
Why? Because it is simply too costly to follow the gold-standard and carry out randomized controlled trials necessary to prove that a drug is more effective than a placebo.
In dealing with the current crisis, should we care whether a drug is more effective than a placebo? No. That level of evidence-gathering should be reserved for new therapeutics where safety is not well established, where the drug is expensive, or when there are other effective treatments available.
If a drug has a long and rich track record of safety, if it’s accessible and affordable, and if there is no other proven treatment that works, it simply shouldn’t matter if patients benefit wholly or partially from a drug’s inherent placebo effect. We have nothing to lose and everything to gain.
Unfortunately, nothing seems to shake a physician’s self-confidence more than realizing his or her patient benefited from a “placebo-effect” rather than from the physician’s excellent science-driven prescribing skills. Physicians’ attitudes, entrenched by the regulatory approach and the high bar of evidence-based medicine, are preventing many COVID-19 patients from benefiting from potentially life-saving therapeutics.
Placebo-phobia is preventing us from tackling COVID-19 head-on, and it is taking lives in the process. As scientists and physicians, we must be humble enough to accept a scenario wherein the placebo-effect may be responsible for part or all of the benefit of a repurposed drug candidate, thus stealing the limelight from science and medicine.
Just like a placebo, many of the limitations we face in the fight against COVID-19 are only in our heads. Patients deserve every chance at having their lives saved, and overcoming our placebo-phobia is critical in providing that chance when nothing remains to be lost but life itself.
