The National Organization for Rare Diseases reports that 90% of rare diseases lack an FDA-approved treatment [1]. Globally, that number increases even further, as 95% of rare diseases lack an approved treatment [2]. Patient recruitment for pharmaceutical clinical trials is challenging, especially for newer therapies targeting rare diseases like cell and gene therapy.
Cell and gene therapies have the potential to improve patients’ quality and length of life drastically, however, these therapies cannot be developed or approved without clinical trial participants. Addressing the issues with patient recruitment for cell and gene therapies is necessary for their advancement.
What are the challenges?
Around 400 million people globally have been diagnosed with a rare disease, or 3.6% of the global population [3]. Experts estimate there are roughly 7,000 rare diseases in existence, means that each disease affects about 57,100 people worldwide [4].
A primary challenge of recruiting patients with rare diseases for cell and gene therapy is that the number of eligible patients is quite small. Additionally, cell and gene therapy clinical trials have very specific genetic or disease-level requirements, such as patients needing to express specific genes or be in certain stage of a disease for study qualification. This decreases the already limited pool of potential participants in a study. Finally, many patients with rare diseases are not aware of clinical trials to even consider participating, usually due to lack of communication from healthcare providers [5].
Given that the pool of possible participants in a clinical study for cell and gene therapies is already small, geographical location is another principal barrier to participation. If a patient with a rare disease participates in a clinical trial, they will more than likely have to travel a great distance. One survey found that 23% of patients choosing not to participate in a clinical trial cited that the trial site was not close enough to where they live or work as their main barrier to participation [6].
Phase 1 clinical trials should have between 20 and 80 patients at least for the study to be effective, phase 2 between 100 and 300, and phrase 3 between 1,000 and 3,000 [7]. Recruiting that many people to come to one location is no easy task. Between the general life disruption, the inconvenience, the travel, the cost of travel, and thinking about managing the disease makes the idea of going to a clinical trial a lot less appealing for many people.
On top of that, as cell and gene therapies are innovative treatments, not all medical professionals have the resources to provide them. This makes them less available to patients dispersed around the globe, as they will likely have to travel to a major city to receive the treatment.
Furthermore, trial recruitment is difficult and time-consuming. Drug developers recruiting for any trial face issues with few eligible participants, difficulty identifying the correct patient population for the trial, obtaining comprehensive informed consent, and trial patients drop out before the trial even begins [8]. Each of challenges are amplified for trial recruitment for cell and gene therapies for rare diseases.
Participation can also mean giving up a current treatment that is providing relief and replace t with a new therapy that may or may not provide the same or better results. This can be a barrier to patient recruitment as well.
Many people with rare diseases experience depression, anxiety, and stress which can stem from living with a rare disease as well as a lack of knowledge about the disease and how to treat it. Some rare disease patients are doubted by their healthcare providers, wrongly diagnosed, or incorrectly treated. All of this can lead to additional suffering beyond the disease itself, which can also cause an inherent distrust in healthcare providers and the healthcare system at large.
Patients who lack trust in the healthcare system are much less likely to feel safe or comfortable trying a new treatment or participating in a clinical trial. They may also worry about the potentially negative side effect that could result from the trial.
Improving patient participation in cell and gene therapies
Attracting more patients with rare diseases to participate in cell and gene therapies, including clinical trials of these treatments, requires evaluating what prevents these patients from participating to begin with. Nothing can be done about the number of patients available to volunteer for clinical trials. But getting more rare disease patients interested in new treatment options will involve making them as accessible as possible.
Patients might be more willing to participate if they are offered money for travel and other expenses. Researchers could also utilise technology. Decentralised clinical trials (DCTs) are more feasible using things like apps to track symptoms or remote monitoring devices to collect data. DCTs will likely lead to an increase in patient participation, as they eliminate the need for travel, making the trial more convenient and comfortable [9].
Researchers should ensure they are communicating with patients that trials are available. They should provide clear information that patients can understand, including a risk-benefit profile to reduce their hesitation toward new drugs cell and gene therapies. They can provide facts and help patients understand why the research is worthwhile. They can also explain to the patients the specifics of the trial, so they don’t have any doubts. This can help build much-needed trust between rare disease patients and medical professionals.
Along the same lines, crafting clinical trials that are patient-centred and providing patient-centred care, in general, could also be useful in attracting rare disease patients to cell and gene therapies. Researchers should ask patients questions about their experiences and let them know the information they provide is considered essential. They can also consider their mental health and involve them in all decisions regarding their health.
Finally, researchers should remind patients of the value of their participation. Without clinical research, advances in medicine would be slow going at best or nearly impossible at worst. Cell and gene therapies have the potential to improve the quality of life and lifespan of both study participants and others with the same or similar conditions. The data recorded in these studies can be game-changing for rare disease patients, especially when trials are robust with lots of participants.
Participation should be as easy as possible on all fronts, including expenses, travel, mental health, and overall care. Listening to patients’ perspectives and letting them guide the study structure or treatment will help to create a more attractive trial.
References
1. https://rarediseases.org/orphan-drug-act-resolution-introduced-in-the-house-of-representatives/
2. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30006-3/fulltext\
3. https://www.who.int/medicines/areas/priority_medicines/Ch6_19Rare.pdf
Jess Lakritz 