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Trial Challenges: Overcoming Objections to Study Placebo Use

by Imogen Cheese
Picture of a study placebo

I was asked to give my perspective on placebo-controlled trials. Using a study placebo presents challenges in recruitment and retention, especially because participants tend to hope that joining a study will lead to a positive treatment response.

As I have mentioned in quite a few of my blog posts, I am a cancer patient. So my thoughts, like my experiences, come from that perspective and admittedly with my own biases. To expand the experience base for this post, I also spoke with additional participants from oncology trials.

The placebo is ubiquitous. Placebos have been used for hundreds of years and were first demonstrated back in 1799. There are currently 30,297 placebo-controlled trials listed on clinicaltrials.gov, of which 5,467 studies are not yet recruiting or actively recruiting.

Study placebos are useful in determining efficacy. They enable a direct comparison between the current standard of care or no action and the introduction of a new drug.

Study drug or study placebo? Participants want to know. 

In placebo-controlled trials, every participant will devote a lot of thought to whether they are getting the active study drug or a placebo. It’s human nature. We watch for symptoms, desperately hoping that symptoms mean a durable response.

No one knows for sure until unblinding. Although clearly many patients I spoke to, most definitely believed they knew whether they were in the placebo arm or the treatment arm. When patients believe they are getting the placebo, they will often wish to opt-out of the trial.

Leaving the study early

A picture of leaving the study early

I recently interviewed clinical trial participants for an industry conference presentation.

Many notable comments stuck out, including this one: Michele decided to leave her Chicago-based oncology study, in part because she suspected she was in the placebo group. “I’d never had any side effects the entire time I did it, and so I really think I was getting the placebo the whole time,” she told me.

She wanted to be on active treatment, and she found another study.

Some participants will even investigate. One woman I know spoke with other participants of the same study online and in the hospital waiting area. She found several were experiencing specific side effects. Since she had none of those side effects, she concluded she was receiving the placebo. Eventually, she requested to be unblinded. The request was refused, and she left the study.

I’ve heard these same scenarios on dozens of occasions, and it’s easy to say these participants should never have left. However, these defections are perfectly understandable since they were oncology patients hoping to receive the study treatment.

Equally understandable were the hospital’s and the sponsor’s reactions. They were very unhappy with the participants. They impacted the study data.

Communication is paramount

In so many areas of life, there is a benefit when we communicate. There are ways we can promote inclusion and involvement:

  • Make sure the patient is aware right at the start regarding the support, monitoring, and value of participation, even if they may receive the study placebo.
  • Make sure they are updated and aware of:
      • What we are using the data for
      • How many patients we are getting the data from
      • How the trial is progressing

I spoke to patients who were no longer in their trials and were sure they had been in the placebo arm. The data is still blinded. They told me they have never been advised, and sadly, they never expect to be informed about what control arm they were in. It is important to follow up with this information.

 Health monitoring is a motivation to stay in the study

Health Monitoring Equipment picture

Many patients I spoke to opted to remain in a trial even when they believed they were in the placebo arm. Many felt they were benefitting from the additional medical care and assessments they received from being in the trial.

One person I spoke to was a carer. There was a noticeable lack of toxicity in her husband’s case compared to others they knew in the trial. She described sitting next to her husband (the patient) at the hospital. What they were convinced was the placebo (in this case, water) perfused for over an hour.

Despite the enormous burden of travel and commitment to take part in the trial, the patient and carer decided to remain in the trial. She told me they didn’t want to cause issues with the hospital team they were fond of. And they believed the additional monitoring and support they received would outweigh the risk.

Studies offer medical monitoring by experienced study teams. Participants who recognize the value in that monitoring are more likely to stay, even if they believe they are in the placebo arm.

The patient burden

Patients very much want to be involved in clinical trials, and as an industry, we should encourage the altruistic and engaged patient.

We should look at the burden. The patient absorbs the expenses of participating, and it is ALWAYS more than just travel costs.

Many have to take several days off work and get assistance traveling to and from the hospital (which may also involve a partner or friend taking time off work). Add to that list child care costs, disruption of family routines, fatigue, and mental strain.

Yet the majority of studies only reimburse for basic travel costs such as fuel or parking. With the rising cost of living, this burden is growing higher. We may see a detrimental impact to study participation over the next few years, specifically around costs, if we in the industry don’t widen the burden perspective.

 I would suggest that a patient who is a willing partner in a trial designed with ALL the patients’ best interests in mind is a better approach. Let’s make the trial design more welcoming, and most importantly, address the patient needs and actual costs.

Tangible tools that help

It is very important to make sure participants are comfortable when they are at the hospital. Water bottles, tote bags, blankets, eye masks, and even puzzle or activity books are always appreciated. These are just some of the ways patients have been engaged successfully when participating in all kinds of studies.

Study materials like thank you cards and contact after the study concludes are things I always encourage. What better way to engage with patients than by making sure they feel appreciated for being involved and letting them know their involvement was effective and vital to the trial outcomes.

Summing up

Let’s never look at the patient as merely a participant or a data point, and think of them always as a welcome and appreciated member of the team.

More on placebos: Check out our 5 fun facts.

 

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