How to Work with Patient Advocacy Groups & Patients

It’s been awhile since I posted anything – sorry about that. Between excessive travel, new projects with new partners, and unexpected foot surgery, time marched on without me! I actually wrote 2 guest posts that I haven’t mentioned, though. Here is the first one:

Get Real with Patients and Their Advocacy Groups at Clinical Trials Arena. It summarizes a talk I gave at their April 2016 Clinical Operations in Oncology Conference.

People ask me how to work with patients and patient advocacy groups all the time.

Short answer: it depends on the disease, and what type of input is desired at different times. The post listed above offers some ideas.

Two more opportunities are also coming up quickly with eyeforpharma:

  1. Join Jamie Roberts from CTTI, Victoria Dibiaso from Genzyme and I on August 4th at 11a EST as we discuss how to Drive Value and make the Patient-Centric Trial a Reality. It’s free!
  2. I’ll also be speaking with many other patient advocates and companies at the Patient-Centered Clinical Trials conference October 10-11th. Be sure to say hi if you see me there.

There are more happenings in this area – look for future posts here on this topic!

Happy Summer…

Patients Want Their Data Shared

Patients also want to be:

  • Respected for their contributions to science and medical advances. Those contributions include samples from their bodies (biospecimens), information (data), experiences (input), and sometimes their very lives.
  • Protected from harm and misuse of sensitive data about themselves, their family, and/or their culture or ethnicity.

As long as we are respected and protected, we will participate in clinical research and learning healthcare systems so researchers can find better ways to treat and prevent diseases and medical conditions.

What & Who

This post focuses on data from past “legacy” cancer clinical trials. The Patient AdvocateProtectionCommittee in the Alliance for Clinical Trials in Oncology drafted a resolution to add the patient voice to the groundswell of support for data sharing.

Why?

  1. People who join cancer clinical trials are often asked to donate their tissue and data for future research.
  2. When patients give consent for research, they expect their information to be shared.
  3. Unfortunately, many hospitals, clinics, academic centers, or research groups will not release information to other researchers, even though patients gave their consent.
  4. This does not honor or respect patients who want to contribute to research.

Your Call to Action

  • Please read the resolution, sign on, and share it with your networks and organizations. While this resolution deals with cancer, its intent is to help all medical conditions.
  • Include patients in data sharing activities.

“Today, oncologists and cancer researchers realize that they can’t [advance cancer progress] alone… What’s required today extends beyond any individual or any individual discipline, beyond medicine itself… It requires somewhat of a change in mindset. It requires a lot more openness – open data, open collaboration and above all, open minds.

– Vice President Joe Biden, ASCO Speech

Thank you!

Esserman & Hwang: TIME’s Top 100 — (And My Top 10!)

Donna Pinto wrote this great post after our meeting last week with other patient advocates, researchers and clinical trial staff to discuss the new PCORI DCIS COMET study that is in development. Thanks to Shelley Hwang, Ann Partridge, Alastair Thompson, and Jennifer Gierisch for including us in the Study Leadership Team!

More DCIS info here.

DCIS 411

Highlights-Esserman-Hwang-TIME100-Blog-270x85What a major milestone this is!

Laura Esserman and Shelley Hwang — named to the 2016TIME 100 Most Influential People in the World!

Why are These Doctors in My Top 10?

From the day I received a DCIS diagnosis and I was told of the very drastic and aggressive treatments, I began to investigate what intuitively felt seriously wrong. I was scared, confused and overwhelmed, but thankfully I soon discovered two breast surgeons leading a “controversial” call for change and discussing the problem of “over-treatment” of DCIS.

Laura Esserman and  Shelley Hwang became my heroes.  They were both boldly taking a stance — challenging the medical status quo when it came to DCIS and calling for radical change. I have been following and promoting their important messages for over six years.

Up until recently the mainstream media didn’t pay much attention to them. Celebrities with DCIS choosing double mastectomies…

View original post 668 more words

How to Solve Diseases with Existing Drugs

My blog guests this week are Amy Conn, Bruce Bloom, and Clare Thibodeaux from Cures Within Reach. Disclosure: I am a member of their Advisory Board, and think that testing older drugs for rare diseases is brilliant!

The power of repurposing

What if the latest treatment for cancer, diabetes or thousands of other unsolved diseases was already available?

Although this might sound too good to be true, “repurposing” existing drugs could make this a reality. Repurposing takes any drug, device or nutriceutical, already approved in one disease, and tests it in a different disease to quickly and affordably improve more patients’ lives.

cures within reach infographicCurrently more than 500 million people worldwide suffer from diseases that lack effective treatments. As a result, global health care costs are growing and patients are suffering. Yet new drug discovery can take 10-15 years and can cost over $2 billion. This process is too long and costly for many patients who needs a solution today.

Instead, repurposing leverages prior investments by finding new uses for “old” drugs. This means repurposed treatments can reach patients in about 3 years and for less than $500,000.

Testing for repurposing sometimes means they are first tested in tissue samples or animal models in laboratories to find accurate dosing. If this pre-clinical research is done, the drug can quickly move into human trials. In some cases, it moves into human trials immediately.

How do repurposing ideas happen?

Repurposing is not a new concept. Doctors often prescribe medications ‘off-label’ when they think the patient may benefit. This happens when there is no approved treatment for a specific medical condition.

  • In fact, 1 in 5 prescriptions (21.3%) written in the United States are for off-label use. The range varies widely, based on the medical condition or patient group. For instance off-label use can be as high as 7 in 10 children for pediatric illnesses, because sponsors don’t typically focus on them. Here is a table with common off-label prescriptions.

Repurposing research can take off-label prescribing a step further by confirming clinical observations through a clinical trial. The data from these trials can then be published in scientific journals, and shared with other doctors to become part of standard treatment.

Other sources

  • Patients also contribute insights when they describe how a drug or supplement that they are taking for one issue impacts a different disease or diagnosis (i.e. “my asthma drug seems to be helping my eczema”).
  • Ideas also come from laboratory scientists, who connect the dots between newly discovered disease information and existing compounds.
  • And in our emerging world of big data, informatics engines can comb through scientific literature to find existing ideas and generate new ideas suitable for immediate testing.

Who pays for repurposing research?

Sometimes, pharmaceutical companies finance repurposing projects.

A case in point: ViagraViagra_in_Pack

Originally tested as a drug for angina, sildenafil failed. Instead, it was repositioned into the Pfizer blockbuster Viagra for erectile dysfunction after patients mentioned this side effect. Sildenafil was still under patent protection and the market was huge, making it a lucrative endeavor. This drug was later repurposed by Pfizer a second time in a different dosage under the name Revatio for pulmonary arterial hypertension.

Too many are orphans

Many repurposed opportunities are based on generic drugs that are often inexpensive and widely available. These characteristics make them ideal candidates for repurposing for patients, but industry doesn’t often pursue them, since there is no clear path to profit. This is where philanthropy plays an important role.

Cures Within Reach (CWR) is a global non-profit dedicated to repurposing research

CWR focuses on improving patient outcomes in any disease with repurposed treatments, while addressing larger needs around global collaboration, and the creation of alternative financial incentives for repurposing.

Successful repurposing

Key In Lock Showing Forbidden Information And Privacy

Since 2010, 13 repurposing projects that Cures Within Reach supported have made a clinical impact. One such project involved repurposing sirolimus, a generic drug originally used to reduce organ transplant rejection, to treat a rare and deadly childhood disease called autoimmune lymphoproliferative syndrome (ALPS).

Children with ALPS carry a genetic mutation that causes some of their white blood cells to multiply and crowd out other types of blood cells. They suffer from enlarged lymph nodes and spleens, increased infections and anemia. Some patients can spend up to 10 days a month in the hospital receiving treatment, placing physical, emotional and financial burdens on patients and their family.

CWR funded research that helped prove that sirolimus produced a lasting positive response in patients, leading to fewer hospitalizations, greatly lowered medical costs and improved quality of life. This result happened in 3 years for about $250,000. Sirolimus has since been repurposed in 5 more childhood autoimmune diseases with similar results.

Ready for more successes with CureAcceleratorTM

Philanthropic funding was critical to this high-impact repurposing research. There are many more opportunities like this one, in which a small “investment” can create a life-saving repurposed treatment.

To find important repurposing opportunities CWR asks:cure accelerator logo

  • How can we help repurposing researchers connect with strong funding streams?
  • Are there financial models other than traditional philanthropy that can help scale this research?

To answer these questions, CWR created an online crowd-sourced platform in 2015 called CureAccelerator.™ Check us out, and watch for another post soon about CureAccelerator.

Repurposing is an important healthcare strategy, both in terms of patient impact and cost savings. As scientists and clinicians learn more about the mechanisms and molecular targets of diseases, repurposing will play an even larger role. The key stakeholders in repurposing, from funders to researchers to patient advocates to industry, all need to work together to drive new “old” treatments to patients.

Learn more about repurposing drugs here.

Make Clinical Trials Better for Patients

There are many reasons why clinical trials don’t work well. A major one is not making them useful or interesting to patients.

I had high hopes when I heard about the recent clinical trial protocol (plan) template from the U.S. Food & Drug Administration (FDA) and the National Institutes of Health (NIHJoint Leadership Council (JLC). Unfortunately, it looks like they just took the traditional clinical trial approaches and set up a template for them.

We can insert PATIENT-centered research now!scales-research-patients

This is OUR CHANCE to include patient-oriented recommendations, not just assistance for researchers and regulators. Please read this post, and make your own comments by 11:59p Eastern on April 17th.

Change the clinical trial protocol template

The template covers phase 2 or phase 3 protocols with investigational new drug (IND) or investigational device exemption (IDE) applications. Here is some background information, in case you’re interested.

“Our goal is to provide an organized way for creative investigators to describe their plans so that others can understand them.”

– Dr. Pamela McInnes, Deputy Director, NIH NCATS

While the FDA/NIH want better organized and consistent plans from researchers so they can review them faster, there is no discussion on how to create BETTER trials for PATIENTS. Since everyone else is focusing on their own interests, we need to bring up PATIENT NEEDS!

Belmont triangleHere are my submitted comments. Please, please, PLEASE take ~30 minutes RIGHT NOW to make your own points (or use mine) and send them in.

My comments – make yours by midnight, April 17!

There are broader issues to discuss, but this is not the place. For now, here is the information I sent to the NIH and FDA Request for Public Comment on Draft Clinical Trial Protocol Template for Phase 2 and 3 IND/IDE Studies on April 16th:

As President of Patient Advocates In Research (PAIR), I have worked with translational, clinical, epidemiological, and healthcare delivery researchers for over 20 years. I offer these comments, based on that experience. These suggestions only touch the surface of far-reaching changes that should be taken to change to a patient-focused clinical trial system. I would be happy to discuss them in more detail with your Joint Leadership Council.

After reading the proposed template, I am not sure how it supports newer approaches to clinical trials, such as those that combine phase 2 with other phases. There is also no discussion about how to make clinical trials more patient-focused. This is an opportunity to actually change the way clinical trials are developed so that they address PATIENT needs, not just those of researchers and regulators. Please consider how this template can satisfy your requirements, focus on patient population needs, and support new approaches to study design as science advances. For example, including explanations or encouraging examples of bucket trials and other newer designs would be useful.

Rather than separate my comments into your categories, I have created a list of overall suggestions, and have indicated when my comments apply to certain protocol sections.

  • First, PLEASE STOP using the words “subject” and “subjects” when referring to people who may or may not be study participants. It should be replaced by “human research participant,” “trial participant,” or another less derogatory term through the entire template. As an example, this term is actually used incorrectly in the Statement of Compliance (p.vi), since the association that conducts the accreditation (AAHRPP) calls it “Human Research Protection Programs,” NOT “Human Subjects Protection Programs.”
  • Include a required, numbered section for some type of Patient Reported Outcomes (PRO) with the study population. This should be included in the Schematic of Study Design (p.viii) and as a complete explanation of the type of PRO that will be implemented. If it is determined this is not possible for some reason, an explanation should be included in the protocol that will be formally reviewed by NIH/FDA.
  • The template is oriented almost exclusively toward drugs. Where applicable, additional information for devices and behavioral interventions should also be included.
  • Good references (pp.a-b) are included to point investigators to useful resources for protocol development, but it might help to categorize them by type of information.
  • A statement should be added to the List of Abbreviations (p.v) so that any and all acronyms used in the protocol will be added to this list.
  • Consider a limit on the number of secondary endpoints allowed. Many secondary endpoints add no value whatsoever for patients, and often add complexity to clinical trials in an attempt to salvage an uninteresting agent or device that will not improve patient outcomes. Your designation on the Protocol Summary (p.vii) of “Important Secondary Endpoints” illustrates this point. No ‘unimportant’ secondary endpoints should be included in a protocol!
  • In the Protocol Summary (p. viii), please add any diagnostics that will be used and whether or not these are being developed concurrently, or are commercially available.
  • Again, replace the word “subject” on the Schematic of Study Design (pp.viii-xi) with a more appropriate and accurate term, such as “research participant.” Examples of biologic testing procedures for concurrent development and/or for eligibility should also be listed, as well as PRO parameters and timing, as mentioned above.
  • Under Key Roles (p.1), there are sometimes designated patient advocates/representatives who play a formal role in the leadership of the protocol. This role should also be mentioned on this page to encourage investigators to include patient advocates. The research nurse assigned to the protocol for the sponsor and site should also be listed  since they are critical not only to the protocol, but also to study participants.
  • A required section in 2.1 Background Information (p.1) of the protocol template should include information about the patient population being studied. Examples that include patient needs and issues will help investigators think more about how to meet patient needs. It should also include what treatment options patients normally have.
  • In 2.2 Rationale, please state that investigators should include a statement on how patient outcomes may be improved by their intervention or study hypotheses.
  • In 3 Objectives and Responses and 4 Study Design and Endpoints (p.3), please require a clear explanation of why a non-inferiority design might have been chosen, that it fits the ethical constructs of studying the appropriate population (e.g. sicker patients instead of healthier), and describes how they will minimize the percentage allowed to be worse than standard treatment. A concern is that non-inferiority designs are misunderstood, and can lower the accepted standard over time without sufficient vigilance by FDA and NIH. Superiority trials should be encouraged and preferred. If a superiority trial is not be possible,  an explanation should be included for formal FDA/NIH review before accepting the clinical trial design.
  • In 4.1 Description of the Study Design (p.3), please add “adaptive design” and other newer design methods in the ‘description (e.g.)’ to encourage investigators to include these designs in their trials. It is also important to encourage crossover and treatment switching for patients where possible. The Center for Medical Technology Policy (CMTP) and its international working group are publishing guidelines in May 2016 to help investigators include appropriate treatment switching. It would also be useful to encourage dose escalation in the same patient when possible if this study design is being used.
  • In 4.2 Study Endpoints (p.3), please add PRO to the ‘e.g. examples’ so investigators will use them in appropriate situations to help determine study endpoints.
  • In 5 Study Enrollment and Withdrawal (p.4), please remind investigators to be as inclusive as possible to better reflect the general population, and to limit test and trial procedures to those that are required to reach study endpoints, rather than traditional convention. Many eligibility criteria become boilerplate items, rather than appropriate criteria for each specific clinical trial. Also, please state that an explanation to justify a limit on reproductive status is required, so that it is treated appropriately, rather than as a traditional exclusion criteria.
  • In 5.3 Strategies for Recruitment and Retention (p.6), please add a section that encourages the return of results to trial participants. This could include how incidental or individual results may be returned, as well as how aggregate results will be disseminated to study participants, their doctors, and the general public. In addition, it is worthwhile to develop plans for the targeted patient population(s), site staff, and referral physicians. This presents a more comprehensive approach to recruitment that has a better chance of succeeding than past approaches.
  • In 5.5 Premature Termination or Suspension of Study (p.7), please add a section that describes how this information will be disseminated to all study participants and their doctors.
  • In 6.2 Study Agent Accountability Procedures (p.10), please include a requirement that explains how study participants will receive the agent/device after the trial has been completed.
  • In 7 Study Procedures and Schedule (p.11), there should also be a statement of how study data will be associated with the study participant’s medical records (both paper or electronic) during the trial and in the future, and if any medical records will be used in data collection. Procedures should include safeguards and privacy protections for all data, biospecimens, images, and other procedures. Data sharing procedures and policies should also be stated explicitly.
  • In 7.3.1 Screening (p.13), it is also important to have investigators describe how they will inform potential participants of their eligibility, including how any test results that determine eligibility will be shared.
  • In 7.3.3 Follow-up (p.14), procedures to update study participants on the trial status and findings should also be included in addition to an expectation of what follow-up visits will entail. It would also be useful to show how they can describe the ability to use local labs and clinics for procedures to make follow-up visits more convenient for study participants.
  • In 7.3.4 Final Study Visit (p.15), the investigator should also describe the information that will be given to the study participant, along with resources that will be available to them. Some of these can be collected and distributed by FDA/NIH so investigators won’t have to re-invent them for each trial.
  • In 7.5 Concomitant Medications, Treatments, and Procedures (p.16), investigators should also ask study participants about any supplements or other complementary/alternative therapies they may use since these have the potential to confound clinical trial data. This should be included on case report forms and tracked throughout the trial.
  • 8.1 Specification of Safety Parameters (p.18) should also include the way that study participants and others will be alerted to SAEs and Unanticipated Problems (UP). It should also require the collection of PROs to ensure comprehensive data collection.
  • In 10.4 Description of Statistical Methods (p.31), please include adaptive and Bayesian statistical examples to encourage their use. Methods for treatment switching should also be described.
  • 11 Source Documents and Access to Source Data/Documents (p.36) should include a description of how study participants’ medical records (all of them) will be validated since multiple records may exist and/or not include comprehensive information. It should also list how study participants will be updated about data sources, and how trial data will be shared with others.
  • 13.3 Informed Consent Process (p.38) should also include the description of plain language and a resource list for health literacy and numeracy principles. It would also be useful for FDA/NIH to create a repository of good informed consent examples of processes and forms for investigators.
  • 14.5 Publication and Data Sharing (p.45) should include a section on how data will be shared, and when types of data will be available to multiple stakeholders, including the trial participants.