Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.
There is a need for new treatment options for interstitial cystitis and bladder pain syndrome (IC/BPS). These conditions have a range of causes and symptoms, and symptoms can be very similar to other conditions. This variation adds complexity to testing new treatments. To meet the needs of patients, the FDA must hold the sponsors’ clinical trials to a high standard that ensures safe and effective treatments.
Criterion #1: We agree with FDA scientists that clinical trials will be much more informative to patients and physicians if they are 24 weeks rather than 12 weeks. While IC/BPS is chronic, the severity of symptoms can fluctuate over time. Patients may use a treatment for years. Longer studies are absolutely crucial because they provide more opportunity to observe long-term treatment outcomes and identify safety signals. Patients deserve that information as part of the process of informed consent so that they can make the medical decisions that are best for them.
#2 The evidence needs to be reproduced in at least two randomized, controlled trials in order to ensure the results are valid. Replication is the key to solid science, as we all know. When scientific studies cannot be replicated patients can be harmed or spend a considerable amount of money on a product that doesn’t help them, and might even harm them.
#3: It will be crucial to carefully clinically define and screen the patient population for the clinical trials, and make sure they are diverse enough to represent patients with these conditions.
In addition to clinical subgroups, consider the effects of demographics. Study participants should be demographically diverse. Major subgroups must have sufficient representation. Most patients diagnosed with bladder pain are women, but it would be inappropriate to test new treatments exclusively or primarily on women. Differences in treatment outcome may be related to age, so study sufficient numbers of older adults. Predefined analysis for demographic or clinical subgroups are important to determine whether effects are consistent across patients.
If the sponsors only demonstrate efficacy and safety in a particular demographic or clinical subset of patients, the indication on the label should be specific to that population. Once a treatment is available, it will likely be prescribed for patients with bladder pain regardless of the approved indication. Nevertheless, the FDA should not contribute to possibly ineffective uses by approving the product for patients who are very unlikely to benefit.
In addition, the clinical trials need to recruit patients from the U.S. and Canada because medical practice differs in European countries.
We support the FDA’s recent focus on patient-centered outcomes. This includes measures of quality of life in addition to specific pain/discomfort and urinary symptoms. All scales should be validated for IC/BPS and should be patient-focused. Of course, it is essential to control for placebo effects with double blind randomized clinical trials.
In conclusion, well-designed clinical trials with a diverse and well-defined patient population should help to determine if a new treatment provides a clinically meaningful improvement that outweighs the risks. Clinical trials should be designed to clearly identify the patient population for whom the treatment is safe and effective and where benefits are most likely to outweigh the risks. These are important data upon which the FDA should make approval decisions, and will enable medical professionals and patients to make well-informed treatment decisions.
The Bone, Reproductive, and Urologic Drugs Advisory Committee (BRUDAC) voted 15-0 in favor of including patients with both IC and BPS in clinical trials for new drugs. The committee provided discussion concerning clinical trial endpoints, patient selection, trial length, and other characteristics.