Last week President Barack Obama asked a bioethics committee to review federal guidelines for the use of human subjects in medical testing. This announcement came in the wake of revelations that the U.S. sponsored experiments in Guatemala the 1940s where people were intentionally infected with sexually transmitted diseases like syphilis and gonorrhea without their consent . Several ethical concerns are raised by human clinical trials, including the use of placebos.
A common feature of modern human clinical trials is a double-blind placebo test. In such a trial, neither the doctor administering the drug nor the patient knows who is receiving the active drug and who is receiving a placebo. The placebo effect is well documented and commonly understood as a mental expectation response to being told that you are receiving a powerful drug. Patients taking a placebo report a variety of responses: some patients on the placebo report feeling better; some report no response and no side effects; others report that they are feeling worse or only experiencing side effects. Some patients, who are not experiencing side effects, believe they are receiving the placebo tend to drop out of studies. Patient drop out is a serious problem and in response, the “active placebo” was developed.
An active placebo is a placebo that causes the same side effects as the active drug, but does not treat the patient’s disease. This helps to convince patients that they are receiving the active drug in the trial, and makes them less likely to drop out (but more likely to report side effects and curative effects of the drug). Active placebos are commonly used in pain trials, giving people symptoms like drowsiness, nausea, or dry mouth.
Patentability under §101
35 U.S.C. §101 requires that a patent be given for any “new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof…” The “useful” requirement of §101 has been used to exclude immoral inventions from patentability. While this category used to include things like gambling machines, today things like suicide machines or a letter bomb would be excluded on an immorality basis. Could an active placebo fail the utility test of §101?
§101 utility requires a practical or specific utility, operability, and a beneficial utility. An active placebo would meet the operability requirement by showing that it did in fact give some people side effects. Presumably, the side effects would have to come from a pharmaceutically active ingredient in the placebo, and not be a result of mental expectation from the patient. The placebo would also pass the practical or specific utility test because it is useful in clinical trials for reducing the likelihood of patient drop out. However, is the active placebo beneficial? It is a device used to trick people into thinking they are taking a curative drug, when in fact the pill does nothing but give them a stomach ache!
The beneficial utility test is a very low bar, and a device that deceives the public may still have a beneficial utility. Here, it may come down to how the claims are written. A composition or compound claim for a drug to induce headaches or nausea would almost certainly be allowed. However, a method claim to tricking patients and taking advantage of the placebo or mental effects of the drug might tip the scales in the other direction. In the European Patent Office, the patent may fail, partly because the EPO expressly allows examiners to consider the morality of an invention, but also because the EPO, under the European Patent Convention, would not grant any method claims filed on an active placebo as being a surgical method.
The use of active placebos presents many regulatory and legal issues that the Bioethics Committee should consider, including patent eligibility. Some other issues involve the informed consent doctrine, the ethics of “do no harm”, and the integrity of clinical trials. No matter what the committee recommends, they will face a tough decision that could affect many clinical study participants in the future.