Thank you for your participation in the PSC Partners Patient Registry. We are happy to bring the second issue of The VIADUCT to you, in case you missed it when it was first emailed recently! Email us at any time with your feedback, input or questions at email@example.com.
In this issue:
From the Registry Director: Moving Research Forward
Clinical Trials: Stay informed with Registry Resources | Fred Sabernick Shares His First-Hand Experience
Boston: An Emerging Hub for PSC Research Home to the Resnek Family Center for PSC Research & the 2022 PSCP Conference
The ROADMAP Initiative: A Map for PSC Patient Engagement
Why We Ask You (Over and Over) How You're Feeling: The Value of Quality-of-Life Surveys
Your Patient File: The Why & How of Uploading a Confirmation of PSC Diagnosis
Registry Data Graphic: Age at PSC Diagnosis
From the Registry Director
Dear Registry Participants,
So much has happened at PSC Partners and in our pandemic world since our first newsletter. We hope that COVID-19 hasn't touched you or your family and that you are managing during this very difficult period. During this time, PSC Partners and the Registry Team have been at work virtually, bringing to life your de-identified data in research studies, moving research forward by assisting drug developers, and forging new collaborations to expedite PSC research.
Our hope is to make sure you feel engaged in the PSC activities PSC Partners is involved in. In this issue, we've included details on clinical trials with an interview with Fred Sabernik who shares his thoughts on his experience with clinical trials. You can read about the Patient Reported Outcome Measure (PROM) project, crucial for clinical trials and the drug approval process, and the ROADMAP Initiative (Research Opportunities And Development Meetings to Accelerate Progress).
The Registry is integral to the patient- and stakeholder-engagement webinars that PSC Partners has been holding since June. We hope that you are already participating in the ROADMAP webinar series. These are interconnected webinars with recordings you can find on the PSC Partners website. Each topic is divided into two parts: the 100 and 200 series webinars. The 100 series webinars are directed at the patient community, and the 200 series webinars are designed for both patients and the medical community.
The aim is to familiarize the patient community with the concepts and research projects that will move the whole PSC community, that is, PSC patients, researchers, clinicians, drug developers, and regulators, towards a collaborative international research network that requires the full engagement of patient representatives. This network will be launched at the PSC Partners Boston Conference next June. We want to emphasize that these webinars are meant to unify the PSC patient community with all stakeholders. This VIADUCT issue includes details on The Resnek Family Center for PSC Research at Brigham & Women's Hospital, Harvard University, in Boston, the location for the next PSC Partners Annual Conference.
By being in the Registry and updating your health information, you are already part of the solution. I hope you can join the ROADMAP webinars so that together, we can create a world where a PSC diagnosis comes with a cure.
Rachel Gomel, Registry Director
Clinical Trials: Stay Informed with Registry Resources | Fred Sabernick Shares His First-Hand Experience
The PSC Partners Registry keeps you informed about clinical trials and research studies, whether you are interested in joining one or are just keeping up with the latest advancements in PSC drug development research. The Registry, nearly 1900 participants strong and growing, is a valuable resource for researchers seeking PSC patients, and connecting patients and researchers is one of its important functions.
Finding Clinical Trials
As interest in PSC grows, so does the number of clinical trials. Researchers have been requesting help in recruiting PSC patients for trials or studies, and the Registry team contacts those participants who might be eligible by email. This in no way obligates a patient to participate, nor does it guarantee acceptance if one applies. Participants who are interested may then contact the research team directly for more information.
a listing of pharmaceutical trial sponsors with whom PSC Partners has worked
a link that is set up to search the clinicaltrials.gov site for all interventional trials for PSC that are recruiting, not-yet recruiting, active but not recruiting, or enrolling by invitation. This site is sponsored by the NIH (National Institutes of Health).
a link to an interactive map of trials (also from clinicaltrials.gov) to explore trial and study opportunities by location.
News releases and updates about clinical trials are posted in the NEWS section of the Registry site, found under the RESOURCES tab.
If you are thinking of applying for a study or trial, be sure to educate yourself. The NIH page mentioned above contains detailed information that patients may want to read before joining a study (click on ABOUT STUDIES).
Inclusion and Exclusion Criteria
Every trial or study has inclusion and exclusion criteria for participation. One reason is uniformity of the test group – the fewer differences among participants, the more confident the researchers will be in the interpretation of trial results. Another reason is safety. Growing children, elderly adults, and pregnant or lactating women are often excluded because the drug was not tested for safety in these populations in the earlier phase of drug development.
In addition, comorbidities (other health conditions), organ dysfunction (in an organ other than the one for which the drug is being tested) and other medications that a patient takes may be cause for exclusion.
Comorbidities and secondary organ dysfunction may put the patient at risk for adverse effects, or the patient may metabolize a trial drug differently, skewing trial results. The medications that a patient takes may influence the outcome or increase the risk of serious drug interactions. Post-transplant patients are often excluded from trials to prevent interactions with their life-sustaining anti-rejection medications.
These exclusion criteria may seem daunting or frustrating, but there has been some new thinking about trial exclusions in recent years. Since many of the trial drugs that come to market are eventually prescribed to the very patients that were excluded from the trials, the FDA has issued guidance encouraging "enrollment practices that would lead to clinical trials that better reflect the population most likely to use the drug if the drug is approved." We may possibly see studies including more heterogeneous populations and new trial models that address the difficulties in conducting rare disease research.
Fred Sabernick's First-Hand Experience with Clinical Trials
Why join trials?When asked why he joins trials, Fred said that the main reason he joins a trial is to see if a therapy that he has heard of may help him. He asks himself, "Can I get some improvement?" A close second, is a feeling of exerting some level of control over a disease that, to that point, had been uncontrolled." A third reason, he said, is "giving back, trying to improve the conditions that people are dealing with going forward. I have not yet said no to a clinical trial that's been offered to me."
Was Fred concerned about worsening his condition rather than improving it as a result of the clinical trial? "It was during the [second] trial," said Fred. "My doctor and I discussed that at some length. I can't say enough about the team that treats me...they treat me with respect; they treat me as an individual; and they recognize the fact that their pat answer is often something I don't accept. Sometimes they have to go a little bit deeper to help me understand some things so that I can actually make an informed decision."
What about other risks? Occasionally, clinical trials require invasive tests such as biopsies. Some patients elect not to accept the inconvenience and the risk that such tests carry. When asked about this, Fred said that he'd experienced only minor issues throughout his trial experiences.
"Medicine is not exact, I get that," he said. "I don't expect [the trial doctors] to be perfect. I expect them to do their best and be prepared for the potentially negative outcomes and be prepared to help me through those. I'm prepared for anything."
"I'm willing to accept a lot for a clinical trial ... I've never had any really negative experiences with them."
Was Fred concerned about getting a placebo instead of the drug being tested?Many people are hesitant to join a trial because of the chance that they might get placed in the placebo control group and not get the trial drug. Fred suspects that he got a placebo in his first clinical trial, but he never learned whether he did or not. He says he looks at the issue pragmatically and reflects that placebos are "an essential part of the science...It's just part of the 'game.'"
How was his communication with the research team?The most recent trial in which Fred was enrolled was run by one of his own doctors, who suggested the trial to Fred. He found that the communication with the team was excellent, and they took his needs and convenience into account. "I discussed side effects and possible conditions pretty much on a weekly basis," he said, "They actually accommodated me [and switched my treatment locations] to a suburban site pretty close to my house."
What would prevent Fred from joining a trial? Fred gave several reasons why he might not join a trial, "If I didn't think that it would have any benefit for me, then I don't know that I would join the trial," he said. "If I had [a less flexible job], that would certainly be a concern ... If the trial was not well-run ... I consider my time valuable." He said that video clinic visits and local lab draws make a trial more appealing. "Much of what is required to be done in clinic can be done virtually."
Closing thoughts from Fred: Choosing to join a trial is an individual decision. "Weigh the risks and benefits to you," said Fred. "But don't forget that you're also helping out your community, and that's not a responsibility to take lightly. We're not a huge patient population, and if we're going to get effective treatments or a cure, it's going to be through clinical trials."
"You get what you give, and in this case, I am happy I am able to give, and I am willing to give."
"Be informed. Learn the pros and cons and then make your decision. But don't be scared. Most of the trials that we [are offered] are past the safety testing stage."
"I am pragmatically realistic about the trial itself. I don't expect miracles. I expect process. That's what a trial is all about. It's about process. If something is found that can help my condition... And if not, maybe it can help somebody else, and if it can't, well, then that's one thing we've ruled out." After a pause, Fred said, "Joining a trial is a conscious, balanced act of self-interest."
But those of us who know and have worked with Fred at PSC Partners know that his definition of "self" includes all PSCers.
Boston: An Emerging Hub for PSC Research
In June 2022, PSC Partners will be holding its patient/caregiver conference in Boston, Massachusetts, a city that has gained special meaning for the PSC community with the recent establishment of the Resnek Family Center for PSC Research, a unique PSC-focused research center in the United States.
The Resnek Center is part of Harvard's Brigham and Women's Hospital (BWH) and was established with a generous gift from Barbara and Frank Resnek, who have a family member with PSC.
When the Resneks were searching for information about PSC treatments, they became discouraged by the limited treatment options available – until they talked to Dr. Joshua Korzenik and his research team at Harvard University. Dr. Korzenik, a member of the PSC Partners Scientific/Medical Advisory Committee, is the director of Harvard's Brigham and Women's Hospital Crohn's and Colitis Center and an assistant professor at Harvard Medical School.
Dr. Korzenik is a thought leader in inflammatory bowel disease (IBD) research, and his leading-edge work gave the Resneks hope that his team could tackle PSC with the same innovative approach. BWH announced the launch of the Resnek Family Center in November 2019, with Dr. Korzenik at the helm as director. He continues as director of the Crohn's and Colitis Center as well - a natural pairing of research interests, since about three-quarters of PSC patients also have IBD.
The Resnek Family Center's primary goal is to develop PSC therapies, and its vision includes establishing "a robust research pipeline" for those therapies. Current areas of investigation include genes, viruses, bacteria, metabolites, vascular causes, and environmental triggers.
The Center's team of clinical investigators and scientists have expertise in gastroenterology, neuroscience, immunology, pathology, and translational medicine. Their goal is "to improve understanding and diagnosis of PSC, build an expansive collection of tissue samples to analyze the disease, and identify existing treatments that could work for PSC."
Dr. Korzenik, principal investigator of an ongoing PSC dietary study, among many other PSC studies, is a Harvard alumnus, earning his bachelor's there before completing his medical degree from Albert Einstein College of Medicine in the Bronx, New York. His residency was at Beth Israel Deaconess Hospital, and he completed his fellowship in gastroenterology and clinical epidemiology at Yale University School of Medicine Hospital. He has authored or co-authored numerous scientific papers and has earned awards for his compassionate care as a clinician.
Dr. Korzenik, along with Dr. Dan Pratt of Harvard Medical School and Massachusetts General Hospital (MGH), will be hosting the PSC Partners annual conference June 2-5, 2022, in Boston. Dr. Pratt is an assistant professor of medicine at Harvard and serves MGH as clinical director of liver transplantation and director of the Autoimmune and Cholestatic Liver Center. Speakers will include experts from both institutions.
More details about the conference and related hotel arrangements will be released in the coming months. Watch for announcements on the PSC Partners main website and social media pages, as well as in mailings from the Registry and PSC Partners. If you haven't joined the PSC Partners mailing list, you can do so at www.pscpartners.org.
One of Boston's more aspirational nicknames is "The Hub of the Universe" – or simply, "The Hub," a name coined by 19th-century poet and physician Oliver Wendall Holmes in a humorous article. When it comes to PSC research, however, the aspiration is quickly becoming a realization. Join us in "The Hub" next year!
The ROADMAP Initiative: A Map for PSC Patient Engagement
With the goal of expanding the patient role in research and drug development, PSC Partners has developed the ROADMAP initiative, a map towards more effective patient engagement. "ROADMAP" is an acronym for "Research Objectives and Development Meetings to Accelerate Progress," and the initiative aims to build a foundation of knowledge and collaboration in preparation for the next PSC Partners annual conference, June 2-5, 2022. ROADMAP meetings, which are online in webinar and discussion format, bring everyone – patients, researchers, clinicians, and drug developers – together at the same table.
The ROADMAP initiative includes:
Educating the patient community on research tools and developments
Expanding the researcher base and strengthening multi-stakeholder communication
Creating opportunities for researchers and clinicians to engage in meaningful discussions with an informed patient community
PSC patients have much to offer researchers. They are the ones who can best describe their symptoms and quality of life; they know the endpoints and outcomes that would mean the most to them; they bring their trusted relationships with medical providers; and they bring a sense of urgency that only a patient truly understands.
Each of the main topics has at least two webinars/discussions, including a "101" session that focuses on the PSC community and a "201" session that includes all stakeholder groups. The first two webinars addressed the topic of a PSC-specific "patient-reported outcome measure" (PROM) and its importance to PSC research. Another article in this newsletter explains PROMs more fully, and you can watch recordings of these two webinars at ROADMAP Initiative 101 and ROADMAP Initiative 201 (live discussion portions are not included for privacy reasons). Past ROADMAP webinars can be found here.
It's an exciting time for the PSC community as the ROADMAP initiative maps out a promising new path for multi-stakeholder collaboration. The June 2022 conference, scheduled to be in person, will have an international collaborative component as it brings together the top international PSC researchers and clinicians. However, for this initiative to be successful, YOUR help is needed! By attending the ROADMAP meetings, you will learn about the latest in PSC research and you will have the opportunity to share your valuable experiences, which is so helpful to researchers.
Visit the PSC Partners website at pscpartners.orgto learn about the ROADMAP initiative and upcoming webinars, the next of which is Wednesday, Sept. 29. More details to be announced soon.
We hope you'll join in regardless of whether you plan to attend next June's conference in Boston. Your participation is valued, and all are welcome and encouraged to take part. Get on board - this train is going places!
Why We Ask You (Over and Over) How You're Feeling: The Value of Quality-of-Life Surveys
While blood and imaging tests play a big role in the study of a rare disease like PSC, researchers and clinicians are showing increased interest in the patient perspective of living with their disease. Such information about living with PSC can be obtained only from patients themselves.
When a patient reports on their own health without any input from a doctor or other expert by a clinician or other expert, this information is referred to as a "Patient-Reported Outcome," or "PRO." When such information is collected in a systematic way through a survey that is rigorously tested and validated, the resulting tool is called a "PROM," or "Patient-Reported Outcome Measure."
Why are PROMs important? In the research and clinical-trial setting, the inclusion of PROs, as measured by PROMs, can steer the direction of research priorities and help set clinical trial endpoints that matter to the patients. For example, with a robust PROM, decreased itching or improved energy levels may serve as clinical-trial endpoints.
In fact, the U.S. Food and Drug Administration (FDA) now expects researchers and industry to incorporate PROMs into clinical trials and have published guidance documents to ensure these PRO tools are acceptable. These efforts aim to ensure patient-focused drug development.
There is an urgent need for a validated, PSC-specific PROM, developed with PSC patient input that can be incorporated in all the phases of the PROM development. PSC Partners, along with experts in the field, is in the process of developing a PSC-specific PROM.
The Registry collects patient-reported outcomes through surveys such as Our Voices Survey and the SF-36 Survey, the latter of which was developed by quality-of-life experts. SF-36 is a general survey that measures a patient's quality of life and is widely used across an array of health conditions. This survey takes approximately five minutes to complete. It is a validated quality-of-life survey and provides important information. Although it is not PSC-specific and therefore cannot be used to support clinical-trials, by taking the SF-36 Survey regularly, you will be contributing data to research and helping experts to develop a PSC-specific PROM. A participant can use the SF-36 Survey to document their own quality-of-life changes over time.
The second quality-of-life survey that Registry participants are asked to complete is the Our Voices Survey, which was created last year in preparation for the PSC Partners October 2020 Patient-Focused Drug Development virtual meeting with the FDA. PSC patients and caregivers spoke about their PSC experience to FDA officials, researchers, clinicians, and drug-developers. Over 800 PSC patients completed the Our Voices Survey for the meeting, and many new registry participants have completed the survey since then. De-identified data informs PROM experts and researchers on what matters most to PSC patients.
A quality-of-life survey has the most value when it is updated regularly to create a record of changes over time. Therefore, we will remind you to update the Registry surveys annually – or when significant changes occur in your health status. A small time investment keeps Registry files current and helps researchers develop trials and studies that accurately address the needs of the PSC community.
PSC Partners hosted two webinars to address the topic of PSC-specific PROMs as part of the recently launched ROADMAP initiative. To watch recordings of these two webinars, please go to ROADMAP Initiative 101and ROADMAP Initiative 201.
Visit the ROADMAP page at the PSC Partners website to learn about this initiative and upcoming webinars.
Your Registry File: The Why & How of Uploading a Confirmation of PSC Diagnosis
A very important piece of your Registry file is your confirmation of PSC diagnosis in the form of an uploaded medical document. This is a very easy process. Each of you who has access to such a record is asked to upload it to your registry file account. If you don't have one, please request one at your next doctor's visit and add it to your existing Registry file.
Why is the confirmation needed? It is reviewed to verify with certainty that registry data represents patients with PSC. Researchers have requested that we do this. We do NOT share the document outside the Registry; it is for internal verification only.
Please take a moment to log in to your registry account at PSCPartnersRegistry.org and see if you have provided this. If you have, it will be listed on your profile dashboard in the Medical Records section.
What can serve as a confirmation of diagnosis? Any MRCP, ERCP, or doctor's report that has your name listed and states that you have or had PSC. The date does not matter; it can be an older document or a recent one.
What format? The file can be -
a screenshot of a document
a photograph of a document
a scan of a document
a document downloaded from an online health portal
To upload the document to the Registry, save your document image or file on your device. Log into the registry, click on the "Add Medical Records" in the attachment section of your profile dashboard, and upload your document file.
While you are welcome to upload multiple documents and use the Registry as a safe place to store your test results, one confirmation document is all that is requested. If you need more help, please email the Registry team at firstname.lastname@example.org.
Thank you for your help in ensuring the accuracy of the Patient Registry!
Don't forget that Registry participants can log into the Registry, click on the VIEW DATA tab, and explore the de-identified data at any time. For example, above we show the reported age at PSC diagnosis.
Established in collaboration with the Office of Rare Diseases Research (ORDR), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH)