Is your clinical trial suffering from the nocebo effect?
As you’ll know, as part of the informed consent process for clinical research, if a placebo is being used in the study, what it is and why it’s important needs to be explained to participants. You’ll also be aware of how important it is to make all potential side effects of the study drug crystal clear to participants. But what if that understanding, or the information communicated in the informed consent process, is actually having adverse effects? Dun, dun dun…
The nocebo effect
Ever wondered where the term ‘the placebo effect’ comes from? Well, it was first defined in modern times in a paper in The Lancet in 1920: the placebo effects of drugs manifested in cases where a real psychotherapeutic effect appeared to have been produced. And today, we still use it when patients think they’re getting the real drug, but are actually receiving the placebo, and recover from ailments in a mind over medicine reaction.
The reverse of this exists, which is known as the nocebo effect. See what they did there? Essentially, it’s when a patient again receives the placebo pill, but this time, exhibits symptoms of the side effects they’ve been told about. Yikes!
Interestingly, findings from a recent study published in the BMJ Journal for Medical Ethics shows that the way patients are informed about the trial they’re taking part in could be harming participation and true outcomes.
Could your informed consent be having a negative effect you didn’t know about?
The study mentioned above discusses the case of a randomised trial of aspirin versus sulfinpyrazone for treating unstable angina. Some patients were made aware of side effects, which resulted in a six-fold increase in the number of people withdrawing from the study because of minor symptoms they believed to be side effects of the drug. It’s thought that being made aware of the side effects prompted patients to expect and subsequently experience them.
Jeremy Howick, PhD, a philosopher and medical researcher at Oxford University, has specifically studied the nocebo effect in regard to informed consent, and believes that those who extensively warn against negative side effects could be fuelling it without realising.
“If a trusted doctor tells you that a drug will give you pain or nausea (or worse!) it increases the chances you will actually experience those things, even if the ‘drug’ is a sugar pill,” explains Howick.
He also believes that the nocebo effect likely impacts people who are quick to look up their symptoms on the internet, or who read about possible side effects to the drugs they’re taking: “People on statins who live in countries with more news stories about statin side effects are more likely to experience them.”
Another study of over 250,000 patients who took placebo pills in clinical trials found that half reported some side effects, and one in 20 dropped out because of a side effect. And some of these were common issues, such as back pain, that can happen whether or not they were taking part in the trial.
John Kelley, Ph.D., and deputy director of Harvard Medical School's Program in Placebo Studies & Therapeutic Encounter, can ground the idea of the nocebo effect in science: “Whenever you look at any randomised control trials, it’s surprising how similarly the side-effect profile for the placebo often mirrors the side-effect profile for the active [treatment]... It’s the power of the imagination. If you ask someone to imagine a visual scene in their minds, you can see on an MRI that their occipital lobes, the parts of their brains involved with vision are activated. If you tell people to imagine doing some physical activity, you’ll see the motor cortex showing activation. Just imagining something is happening is enough to activate those portions of the brain associated with that thought, or worry, or pain.”
Another important consideration for your informed consent process
Making your clinical trial’s informed consent process clear and concise, yet thorough enough to meet all legal requirements is difficult enough. And now you have the nocebo effect to deal with too.
It’s causing an ethical dilemma for healthcare professionals across the board. Inform patients of potential risks and side effects and they could believe they’ll experience them regardless. Don’t tell patients the risks and you could be sued for malpractice for violating informed consent laws. Clearly, not fully disclosing all information isn’t an option. So, what is the solution? According to Jeremy Howick, the solution lies in rethinking the way that side effects are communicated, through positive framing.
“You can tell a patient, ‘10 percent of the people who take this drug have a negative side-effect,’ or you can say, ‘90 percent of the people don’t have any negative side-effects,’” Howick explains. “In both cases, the information is the same, but the first way leads to more reported side-effects.”
Need help overcoming informed consent challenges?
Then we can help. Firstly, check out our white paper where we take you through the fundamentals of informed consent processes, clarify the legislation you need to consider, offer insight into psychology techniques that can enhance your strategy, highlight the biggest issues you may face, and provide guidance on how to create an effective informed consent process.
Or let’s just have a chat? We’re experts in creating informed consent processes designed with the patient in mind: a clear and creative approach that’s useful for patients and can aid enrolment into your clinical study.