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PWS Clinical Trials Consortium: 2017 Update

This blog highlights the 2017 work of the PWS-Clinical Trial Consortium in addressing unmet needs regarding PWS clinical trials.

pws-clinical-trials-consortium-2017-update.jpgThe PWS-Clinical Trial Consortium (PWS-CTC) combines the expertise and perspective from multiple disciplines and stakeholders, bringing together members of academia, industry, and patient organizations from around the world in order to address the unmet needs of clinical trials. PWS-CTC was launched in 2015. This blog describes highlights of the consortium's work to date.

While the increasing number of therapeutic agents currently being tested in clinical trials for PWS opens avenues for effective therapies in the near future, several key challenges need to be resolved ensure the success of upcoming and future trials for PWS:

  • Better understanding the evolution and variability of symptoms between individuals with PWS (the natural history of PWS)
  • Developing new meaningful outcome measures of treatment efficacy (clinical trial endpoints)
  • Developing a structured approach to measure the level of risks caregivers and individuals with PWS are willing to take with new therapeutics (benefit / risk assessment)

To address the needs of clinical trials, working groups have been developed around two main goals:

  1. Develop new measures to assess the efficacy of a treatment against hyperphagia and behavioral challenges
  2. Incorporate the voice of patients and caregivers in the decision-making process for new treatments for PWS

The Challenge of Measuring Hyperphagia

Measuring a treatment’s effect on hyperphagia within the limited time-frame of clinical trials is challenging. While body max index (BMI), DEXA and weight are useful as proxy measures for obese individuals, they do not directly measure hyperphagia and they are inefficient measures for individuals whose weight is under control. Additionally, these measures do not capture food-seeking behaviors that are characteristic of individuals with PWS.

The hyperphagia questionnaire developed by the Dykens team in 2007 is currently the most used outcome measure in clinical trials for hyperphagia in PWS. Although it provides a quantifiable measure of hyperphagia, it does not capture all the challenges that are associated with food-related behaviors. For example, the strategies that are used by caregivers to control the food-environment of individuals with PWS are not well documented and may mask the degree of hyperphagia and other food-related behaviors.

In this context, a PWS-CTC working group on trial endpoints (Dr. Lauren Schwartz Roth, Dr. Nathalie Kayadjanian, Dr. Anastasia Dimitropoulos, Dr. Jessica Duis, Mr. Evan Farrar, Ms. Hailee Hunt, Ms. Elizabeth Roof, Dr. Parisa Salehi, and Dr. Theresa Strong) led by Elizabeth Roof has developed the Food Safety Zone Questionnaire to capture strategies developed by caregivers to control food behaviors. The questionnaire was developed based on the input of caregivers, tested amongst 128 families, and is currently being analyzed. The goal is to validate the questionnaire, so it can be used in conjunction with the HQ to better assess food-related behaviors in a clinical trial.

Incorporating the Patient and Caregiver’s Perspective

A major focus of the PWS-CTC is to include the patient and caregiver`s perspective into the development of new therapies for PWS. The voice of the patient community is critical to understand the unmet medical needs of our population, establish priorities and value assessments, and frame the benefit-risk analysis of new drugs. Two exciting projects have been launched by the PWS-CTC to document the views of caregivers on how PWS impacts their lives and how they weigh the benefits and risks of new treatments for their loved ones. These studies will guide pharmaceutical companies, regulatory agencies (such as the FDA), and insurance companies in addressing the needs of the PWS community.

Last year, a PWS-CTC working group on incorporating patients' and caregivers' voices (Dr. Lauren Roth, FPWR; Mr.Evan Farrar, PWSA-USA; Dr. Theresa Strong, FPWR; and Dr. Nathalie Kayadjanian, FPWR) performed a study to measure the levels of burden in caregivers of individuals with PWS. Using the Zarit Burden Interview (ZBI), a questionnaire that is widely used to measure the burden of caring for individuals with a disability or chronic illness, we found impressively high levels of caregiver burden in PWS. Based on the responses of 142 caregivers, it appears the caregiver burden is highest as the person with PWS ages into the teenage and younger adult age groups. The burden of PWS adversely affected marriage or romantic relationships, caregiver’s ability to work, caregiver`s sleep and mood.

This study which has been submitted to an international peer-reviewed journal, drew the interest of our industry partners to incorporate the ZBI as an exploratory outcome measure in clinical trials for individuals with PWS. The underlying assumption is that a new drug that would improve the health of individuals with PWS would also reduce the burden on caregivers. Several questions, however, need to be addressed before caregiver burden measurement can be tested as a part of future clinical trials. These include: How does caregiver burden vary over time?, What aspects of PWS contribute to the caregiver burden? and Is there a relationship between caregiver burden and hyperphagia (excessive hunger)? To address these questions, we launched a new survey, “Impact of PWS on Caregiver." The survey is still open and we are seeking your help to fill the survey. The results of this survey will help our industry partners to incorporate the ZBI as an exploratory trial endpoint in their upcoming clinical trials.

As part of the drug approval process, the FDA considers a structured Benefit-Risk Assessment to weigh the possible benefits of a drug compared to the risks (eg, possible side effects). The PWS- CTC is seeking to inform the FDA Benefit-Risk assessment for potential PWS treatments by documenting the patient and caregiver`s perspective on the need for treatments to improve PWS symptoms, and the level of risk that families are willing to accept (eg, what risk of side effects would be acceptable for a drug that is effective).

Dr. John Bridges at Johns Hopkins University is a pioneer in this area of research, and has worked collaboratively with many patient communities to provide the patient perspective on drug development. He and his team have been working with the PWS-CTC since its inception to develop an online assessment to capture the diversity of perceptions in the PWS community on treatment needs and risk tolerance. Recently, they launched a broad national Treatment Preferences survey. The results are being analyzed and will be shared with the FDA, the PWS community and other stakeholders, and will provide important guidance on the needs of the PWS community.

The diversity and complexity of the clinical manifestations of PWS along with the life-long impact of PWS on individuals with PWS and their caregivers are often difficult to convey to external healthcare stakeholders who are not familiar with PWS. The PWS-CTC has collaborated with Partner-Films to produce a short 20-minute film to illustrate the complexity and challenges of PWS on the individual with PWS and their caregivers. Because the characteristics of PWS change significantly over the lifetime of the person with PWS, the film portrays three families across different ages (infant, child, adult). The film has been developed for healthcare professionals and providers. These include: regulators (FDA, EMA) who will be evaluating risk / benefit of new drugs or devices for PWS; insurance providers when discussion about treatment reimbursement will take place; pharmaceutical companies seeking to understand the unmet medical needs in PWS; investors seeking to better understand PWS; those in the scientific and medical community interested in learning more about PWS.

The film`s main goal is to enhance the viewer’s understanding of PWS, including clinical complications, behavioral and mental health challenges, and the social, financial and emotional constraints that PWS places on individuals and their families. While it is not meant to reflect the story and specificities of each family impacted by PWS, the film aims to share a realistic representation of PWS that is neither overly dramatic nor downplays the real impacts and costs of the disorder. It was shown for the first time during the PWS-CTC annual conference in Orlando and was very well received by the audience. The film is being finalized and will be available soon.

Two years after its creation, the PWS-CTC is delivering its first important results that illustrate how a unique collaboration between experts from industry, academia and patient representatives can address effectively challenges of clinical trials. The internationalization of the consortium and sharing of information is also beneficial to the entire PWS community. We would like to thank our families and caregivers for their participation in our studies. The continuous involvement of families and caregivers has been and will be key to the success of the PWS-CTC.

For updated information on PWS clinical trial opportunities and to sign up for a monthly PWS Clinical Trial Alert, visit our PWS Clinical Trials page

PWS Clinical Trials

Topics: Research

Nathalie Kayadjanian


Nathalie Kayadjanian, Ph.D is an expert in translational biomedical research. A neuroscientist by training, she has extensive R&D experience in academia, biotech, and the pharmaceutical industry in Europe and the USA. Nathalie has occupied top management positions in patient-driven non-profit organizations, developing and implementing strategies to accelerate the development of innovative therapies for rare diseases.