Earlier this month, PPMD announced a partnership with BIO to develop a set of general guidelines and recommendations that stakeholders can use to design and execute disease-specific patient preference studies. With PPMD's history designing and conducting patient preferences studies in Duchenne, we believe strongly that our experience will help other diseases capture patient preferences in their communities.
By Erin McCallister, Senior Editor
Published on Monday, December 21, 2015
Facing calls from its members and patient groups for a framework on how patient preference studies for drugs should be designed and executed, BIO enlisted Parent Project Muscular Dystrophy to help create a set of general guidelines and recommendations that stakeholders can use to design and execute disease-specific patient preference studies.
Patient preference research is grounded in the notion that patients have distinct preferences about the trade-offs and risks inherent in medical decisions, which are frequently different from the choices physicians would make.
The research methods are well-established and have been applied in healthcare settings for 25 years, but their use to inform medical product development and regulation is quite new.
Only one medical product has been approved based on data from patient preference studies. The Maestro Rechargeable System from EnteroMedics Inc. missed the primary endpoint in a trial to treat obesity. But FDA's Center for Devices and Radiological Health (CDRH) was able to approve the device after a preference study conducted by CDRH showed that a group of patients would accept the risks associated with the device for the amount of weight loss it was expected to provide.
CDRH later issued a draft patient preference guidance outlining qualities of patient preference studies, recommendations for collecting patient preference data, necessary steps to get patient preference data included on a device's label and hypothetical examples that illustrate how patient preference information may inform the center's regulatory decision making.
BIO and PPMD will draw upon the CDRH's work and other successful patient preference studies to identify what practices are exportable to drugs.
The group's recommendations are expected to be available in a white paper early next year, and there are already patient groups and companies eager to use the tools.
Formal patient preference studies can provide hard data on the specific benefits, risks and harms patients care about and quantify both the relative importance of these factors, and the willingness of patients to make trade-offs among them.
Preference studies also can identify and characterize subpopulations that might benefit from a product — and populations for whom no amount of benefit would outweigh the risks.
The data can also help companies and regulators understand the clinical need, and the product characteristics and data benchmarks necessary for success.
In the majority of preference studies, patients are offered a series of hypothetical choices to elucidate and quantify their trade-offs. For example, a study could offer patients a set of hypothetical product profiles that have varying levels of benefit and toxicity. Based on patient responses related to their preferred regimens, the study can elucidate how much toxicity patients are willing to tolerate for a given benefit.
The CDRH guidance notes that patient preference studies can be used throughout a device's life cycle (from discovery to launch and beyond) and outlines when such studies are most appropriate: when multiple treatment options exist but no one option is clearly superior for all preferences; when the evidence supporting one option over others is considerably uncertain or variable; and/or when patients' views about the most important benefits and acceptable risks of a technology vary considerably within a population.
There are some obvious differences between the ways devices and drugs are developed, which would be expected to translate into differences in the ways preference research should be designed and used. But PPMD doesn't think it will be a "heavy lift" to translate the CDRH guidance into something that could also be applicable to drugs.
"There may be slight differences, but nothing substantial," said Ryan Fischer, SVP of community engagement at PPMD.
PPMD designed and conducted patient preferences studies in Duchenne muscular dystrophy (DMD) that helped to inform draft guidance written by PPMD and eventually adopted, almost in its entirety, by FDA this year.
Based on input from a handful of caregivers, doctors, academics and drug companies, PPMD and academic collaborators designed a study to assess the six attributes of a drug most important to patients: effects on muscle function and life span, knowledge about the drug, nausea, risk of bleeds and risk of arrhythmia.
The study used a best-worst study design in which caregivers were asked to pick the "best" and "worst" attribute of a hypothetical treatment. The study found that the 124 participating caregivers ranked the ability of a drug to slow or stop disease progression as being the most important (28.7%) followed by the risk of arrhythmia (22.4%). Results were published in 2014 in Clinical Therapeutics.
"They prioritized slowing disease progression over adding years to life," said PPMD President and CEO Pat Furlong.
A subsequent study in adult patients with limited arm function found that the highest priority for these patients was resolution of cough. "This can lead to infection, and if your chest is full of secretions, you can't call out for help. So cough is a critical factor in terms of communication," Furlong said. The study results have yet to be published.
The DMD guidance FDA issued includes endpoints that are measures of disease progression like timed function tests and respiratory endpoints.
PPMD is now working with patients and caregivers to assess their preferences over the course of the patient's disease "to see if it changes with progressive disease," Furlong said.
"PPMD has paved a path to elevate the patient voice, and we believe other stakeholders can learn from their incredible efforts," said Lauren Neff, BIO's managing director for alliance development.
Based on PPMD's preference studies and other examples, the patient group and BIO will assemble a list of considerations and processes stakeholders can use to design and execute patient preference studies.
"The idea is to provide best practices for studies that could be used by FDA in a consistent and rigorous way that is the same across divisions. So while it won't be the exact same as CDRH's guidance, because drugs and devices are different, we will take some learnings from what they have done and what is different in the devices and drugs area," Furlong said.
The best practices will include recommendations for how to include stakeholders in the design of studies and the validation of survey tools through an iterative process.
"You have to be sure that you're reflecting what is meaningful to the patients, so you have to have all of these checks and balances throughout the process," Furlong said.
The best practices also will address how to conduct scientifically rigorous analyses that can quantitatively assess things like risk tolerance.
"One of the things the best practices will explore is what methodologies to use to arrive at quantitative results. It is much different than market research, and we want to make sure that the best practices acknowledge this," Furlong said.
The document also will provide recommendations on how to identify social scientists who have the skills to conduct these analyses, and it will include questions companies or other stakeholders might consider before designing a preference study.
"The questions that will need to be asked are going to vary considerably depending on what the disease is," Neff said. "There is no one-size-fits-all model and that in some instances, a patient preference study may not be necessary."
BIO and PPMD will seek input into the best practices from FDA.
"Our intention is for this to be an iterative process with FDA, and they have been very receptive and encouraged by the development," Neff said.
Furlong added: "We can't develop these if FDA doesn't agree that these are the best practices. So we'll share what we know and are learning with FDA and get their input. We don't want to spend our time doing one-offs of everything and not meeting a standard that FDA can integrate into the review."
PPMD and BIO plan to meet with Center for Drug Evaluation and Research (CDER) Director Janet Woodcock next month.
The partners expect swift uptake of the recommendations among companies and patient groups.
"We're seeing a lot of patient groups that would like to replicate what PPMD has done," said National Health Council CEO Marc Boutin. "From the company perspective, the document will provide opportunities on the best ways to go and gather data that would be more specific to a product or disease area."
Boutin is a member of the initiative's expert review committee.
"We anticipate that there will be a series of guidances around preference studies — making them, how do you present them to FDA, whether they make it into the benefit-risk framework — and then there will also probably be guidance that will evolve on the methods used and in specific disease areas. All of which will be informed by BIO and PPMD's activities," said Boutin.
Companies and Institutions Mentioned
Biotechnology Industry Organization (BIO), Washington, D.C.
EnteroMedics Inc. (NASDAQ:ETRM), St. Paul, Minn.
National Health Council (NHC), Washington, D.C.
Parent Project Muscular Dystrophy (PPMD), Hackensack, N.J.
U.S. Food and Drug Administration (FDA), Silver Spring, Md.
Cukier-Meisner, E. "Patients lead the way." BioCentury (2015)
FDA Center for Devices and Radiological Health. "Patient preference information — submission, review in PMAs, HDE applications, and de novo requests, and inclusion in device labeling." (2015)
Peay, H., et al. "A community-engaged approach to quantifying caregiver preferences for the benefits and risks of emerging therapies for Duchenne muscular dystrophy." Clinical Therapeutics (2014)
Unsigned commentary. "Back to school: Changing the subject." BioCentury (2015)
Usdin, S. "Would you rather?" BioCentury (2015)