Now that the first therapy for NASH (MASH) is available in Madrigal's Rezdiffra it raises the question of how do we design future clinical trials.

As a patient, would you enter a trial knowing that you might get a placebo when a drug is available?

We all know that to make more progress in treatments we have to be able to run the trials, but how do we ethically ask patients to take an unknown drug when a useful one exists?  As we go forward, we will be advising drug researchers about how liver patients feel about this question.

The issue of using placebos in clinical trials, especially when effective treatments may already exist, presents a multifaceted dilemma that encompasses ethical, practical, and scientific dimensions. Here are some of the pros and cons of such an approach.

Pros

1. Controlled Scientific Rigor: Placebos are critical for maintaining the scientific rigor of clinical trials. They allow researchers to effectively compare the therapeutic impact of a new treatment against no treatment or standard care, thereby ensuring that the benefits observed are truly attributable to the treatment being tested.

2. Understanding Placebo Effects: Including placebos helps in understanding the placebo effect, a well-documented phenomenon where patients experience improvements in their condition simply because they believe they are receiving treatment. This understanding is crucial for parsing out psychological from physiological effects in research findings.

3. Regulatory Approval: Many regulatory bodies, such as the FDA, require placebo-controlled trials as part of the approval process for new medicines. This ensures that only treatments that offer significant benefits over existing treatments or placebos make it to the market.

Cons

1. Ethical Concerns: The primary ethical concern involves potential harm to patients who receive a placebo instead of an available effective treatment. This raises questions about the balance between individual patient welfare and the pursuit of scientific knowledge.

2. Misplaced Trust: Patients entering clinical trials often do so with the hope of receiving a new and potentially better treatment. When they receive a placebo instead, it can feel like a breach of trust, possibly undermining their faith in the medical system.

3. Equity Issues: Placebo use can also raise equity issues, particularly if the trial excludes individuals who cannot afford the standard treatment. This can skew the trial population and potentially limit the applicability of the research findings to a wider patient population.

The use of placebos in clinical trials, while scientifically justifiable, is laden with ethical complexities. It necessitates a delicate balance between advancing medical science and ensuring patient safety and well-being. We must navigate these challenges thoughtfully, leveraging ethical frameworks to guide decision-making.

Give some thought to these issues.  As trials are developed we will ask you to help us by participating in occasional surveys.