Challenges of Recruiting: Reflecting on Sham-Controlled Surgery Trials?

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By Danielle Buchanan

Double-blinded clinical trials are the main way we assess potential treatments. Over the last several years, we in the HD clinical trial space have been blessed to be involved in many different treatment trials, ranging from oral medications, intravenous infusions, intrathecal medications, and now neurosurgical treatments. These neurosurgical treatments are delivered directly into specific brain regions of an HD patient. This will be the first introduction of this type of treatment in HD patients, so we truly don’t know the clinical implications, but it is an exciting new opportunity.

One of the unique challenges that coordinators face is the need to explain to interested patients about the ‘placebo group.’ The placebo for these types of studies involves a sham (placebo) neurological surgery procedure. In this procedure, patients typically have burrholes in the skull, and may undergo anesthesia, but do not undergo brain surgery.

Over the last six months, my coworkers and I have been fielding questions from patients about this potential new therapy. Patients will express excitement for a possible cure, and want to know more about these clinical trials. In our recent experience, many patients express concerns about the invasiveness of the procedure, time commitment to these types of studies, the implications regarding the possibility of being in a sham group, and the relative lack of safety data. A coordinator must be proficient in how to answer these types of questions — so here are my top line reflections on this issue.

GREATER KNOWLEDGE, GREATER PARTICIPATION

As a clinical research coordinator, I often educate patients and their caregiver enough on the trial to aid them in deciding on participation, mindful that I must not persuade them unfairly. This can be a very difficult process and due to balancing potential reward versus the risk of procedure, a patient may or may not decline participation.

Based on a study by the Department of Neurology at Boston University, published by the Movement Disorder Society in 2008, it was found that their more educated patients were able to use “societal prospective rationales” to generate a more positive opinion about a sham-controlled surgical research study. Based on that data, as a coordinator, my job is to present the information clearly to all patients, regardless of their educational level. I do this by creating a consent form in clearly stated lay language about the drug and the study procedures. The level of complexity of neurosurgical trials is very high, so making sure the patient can understand is key, and can be a challenge. Overall, it takes time, and coordinators need to be educators and not feel rushed in reviewing the study with them.

THERE ARE BENEFITS OF A PLACEBO

Whether there is a sham or real surgery, the placebo effect is a real effect. A patient could perceive as much positive benefit from a surgery in the placebo group as if they received an experimental medication. One study found that up to 35 percent of patients demonstrated a therapeutic placebo response to the sham surgery in an internal mammary artery ligation surgical trial for angina pectoris.

These mimic responses found in other possible placebo therapeutic interventions, especially in Parkinson disease.

There are many controversies about the ethical precedent that sham surgical trials face, as well as blinded clinical trials in general. According to the Nuremberg Code, an experiment should avoid all unnecessary physical and mental suffering and injury. I believe many patients view clinical trials skeptically. Many are not aware that study protocols are carefully reviewed by the FDA, and at each individual site’s Institutional Review Board. IRBs must determine whether there is enough information to conduct a trial safely without any ethical concerns. As clinical coordinators, we need to discuss this with our patients thoroughly when talking about all clinical trials, but more specifically, more invasive trials.

When patient safety is carefully protected, sham surgery placebo groups improve the quality of end results in clinical trials across the disease spectrum. Sham surgery is the only means we have to prevent procedure bias.

DECIDING TO PARTICIPATE

As our patients come in to learn about the various clinical trials, their responses vary across the board. The idea of ASO injections stops many people in their tracks. I remember one patient who simply said she did not want to endure a brain surgery, regardless of whether the drug could be a positive treatment for HD. Particularly patients whose disease has not progressed far may express safety concerns about being a part of any phase 1 trial, saying they do not want to be one of the first humans to receive the drug. Some patients want to participate, but only in oral or intravenous infusion trials.

Others, across various stages of the disease, are eager to get on board. We have many patients who have said, “I am willing to do everything it takes to participate in research to help the future generation,” or “I want to get every ounce of hope that I can get, even if I have to get a sham surgery before getting the drug.”

The HD community is one of the most hopeful and inspiring groups of people I have ever met. They are so eager to hear about a potential cure because this disease has affected their family over many generations. As a coordinator, it is a privilege to take this journey with them.

 

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