ADAPTABLE: Answering an Important Clinical Question while Testing a New Approach to Conducting Pragmatic Clinical Trials

In April, Ty Rorick and Lisa G Berdan of the ADAPTABLE Coordinating Center at Duke Clinical Research Institute (DCRI) visited the Research Action for Health Network (REACHnet) team. “REACHnet has developed a very clever way of using tablets in some of their clinics to help reach potential participants previously identified using the computable phenotype. They have just enrolled their first ADAPTABLE patient and we’re very excited to see how tablet technology can help engage participants early in the screening process” said Lisa G Berdan, Director, DCRI Global Cardiovascular Outcomes Trials.

In this feature of Ask ADAPTABLE, Beth Nauman, Research Director at REACHnet, shares the network’s role in the National Patient-Centered Clinical Research Network (PCORnet) and ADAPTABLE.

BACK ROW FROM LEFT: Rahul Jain, Thomas Markey, Prasad Patil, Kyle Bradford, Tom Carton, Beth Nauman FRONT FROM LEFT: Lindsey Rudov, Lindsay Hendryx, Elizabeth Crull, Iben McCormick-Ricket, Autumn Coleman
BACK ROW FROM LEFT: Rahul Jain, Thomas Markey, Prasad Patil, Kyle Bradford, Tom Carton, Beth Nauman FRONT FROM LEFT: Lindsey Rudov, Lindsay Hendryx, Elizabeth Crull, Iben McCormick-Ricket, Autumn Coleman

What inspired REACHnet to join PCORnet?

At the Louisiana Public Health Institute, we had already established community partnerships that we engaged in our public health programming and research, so when we heard about PCORnet, we were excited about the opportunity to work with partners throughout the country on a national-level, innovative health research initiative. Our mission aligns well with PCORnet in that the primary objective of REACHnet is to make research more efficient, more informative, and less costly by harnessing the power of large amounts of health data and patient partnerships.

We began with an initial 18-month project period building health system partnerships, information technology solutions, network governance, and streamlined regulatory processes (e.g., human subjects’ protection) to establish a functioning clinical data research network (CDRN). The network was first called Louisiana Clinical Data Research Network (LaCDRN), and then we expanded into Texas and changed our name to Research Action for Health Network (REACHnet).

 Why do you think the ADAPTABLE study is important?

I believe ADAPTABLE is important for three main reasons:

  1. Direct impact on health care—results of the ADAPTABLE study will directly impact the health care of millions of Americans and provide evidence to answer a simple question: Which dose of aspirin is more effective for preventing heart attacks and strokes in people with heart disease, a leading cause of morbidity and mortality in the U.S.? Moreover, daily aspirin therapy is a highly cost-effective clinical intervention for preventing cardiovascular disease related events.
  2. Demonstrate the capacity of PCORnet —In ADAPTABLE, we will be answering an important clinical question while simultaneously testing a new approach to conducting pragmatic clinical trials. We will leverage a national research infrastructure to test streamlined and innovative processes for identifying and recruiting eligible patients, obtaining informed consent electronically, and collecting data directly from participants through an online portal. ADAPTABLE also provides an opportunity to put our partnerships into practice and learn from one another. The CDRNs involved communicate and share tips, resources, and best practices. We can also learn from each other on what does not work and what challenges we encounter and possible solutions. Learnings from ADAPTABLE will ultimately be used to strengthen the PCORnet infrastructure for future large-scale trials.
  3. A classic example of patient-centered comparative effectiveness research (CER). In ADAPTABLE, we have a head-to-head comparison of two doses of aspirin, a medicine that people are familiar with and a design that can be used to easily conceptualize CER for both scientific and lay audiences. What makes CER different from other clinical research is that we are not using a placebo, we are studying the effectiveness, risks, and benefits of two doses of a currently available treatment. ADAPTABLE provides a relatively simple model that we can use to illustrate the potential impact of CER on health care decision-making by clinicians as well as patients.

How does clinical research benefit from patient partnerships?

Patient partners are invaluable in the research process. Their perspectives are really the most important of all involved, because clinical research relies on patients’ willingness to participate as research subjects, which requires generosity of time, information, and their bodies—these are no small things to voluntarily lend to research for the greater good of other patients and to the overall healthcare field. Patient partners ensure that scientists understand and incorporate patient preferences in the design and implementation of clinical research, which hopefully makes participating in studies seem more attractive and valuable to patients. Including patient partners in clinical research may also enhance the trustworthiness and utility of results that are then more likely to improve clinical practice and health outcomes.

In ADAPTABLE there is a team of people called the Adaptors who have coronary heart disease and are part of the research team and members of the executive and the steering committees. The Adaptors are supported by the Health eHeart Alliance and helped design the protocol, consent form, and website content. The Adaptors will provide ongoing review of study materials and will help disseminate study results to the community.

 How does REACHnet collaborate with their Adaptor?

We have met with our patient partner several times in-person and on conference calls, and we correspond regularly by email. He reviewed our recruitment materials for ADAPTABLE, including: 1) an informational video shown to eligible patients on tablets, 2) a postcard given to eligible patients in clinic, and 3) a recruitment letter that will be sent by post or email. He helped ensure that the information in these materials was clear, sufficient, and concise. He also helped select attractive graphics to use on the postcard and in the video. Most importantly, our Adaptor drafted a reminder email that will be sent to patients three days after the first recruitment email if they haven’t yet enrolled. The message is written personally from him and includes a short description of his experience as a patient with CVD and reasons why he thinks it’s important for patients to join ADAPTABLE. The email will include a photo of him. We hope that this personal touch will be of interest to our target patient population and convey that this study is meant to benefit millions of patients with heart disease.

What did you and your team do to prepare for institutional review board (IRB) review and approval?

Preparing our partner IRBs for involvement in PCORnet studies and establishing good relationships are our keys to success in receiving IRB approval quickly for ADAPTABLE. Early on, we convened an IRB workgroup where we were able to establish relationships with representatives from our partner IRBs. We proactively introduced ADAPTABLE to the workgroup and learned early on what questions and concerns the IRBs had about the study. We asked: “What information do you need from us?” What are your concerns?”

One of the concerns raised was patient understanding. Due to the use of self-directed electronic consent, the IRBs wanted assurance that participants would understand the study and what is expected of them if they decided to participate. Knowing this information upfront, we provided a “walk-through,” a demonstration of how a participant would learn about the study and how their comprehension would be assessed prior to signing consent. Our site and co-principal investigators are great champions of the study and were involved in these conversations with the IRB representatives. We were able to have face-to-face discussions and readily provide information that would address concerns and questions in advance of the IRB review.

What tips or information would you recommend for a smooth and quick contract execution?

Direct communication is the primary tip I would recommend to others. Instead of addressing issues via e-mail, I set up conference calls with our partners’ legal representatives, REACHnet’s contracts manager, and myself so we could efficiently address questions from all parties in order to execute the contract quickly. Without these calls, I would have had to relay information among those involved that would potentially result in further questions and delay the timeline. I wanted to reach an agreement on the terms quickly so we could keep working on plans for implementing the study.

The ADAPTABLE study is funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (Contract Number: ASP-1502-27079). ADAPTABLE is the first demonstration project to be conducted through PCORnet, the National Patient-Centered Clinical Research Network. PCORnet is a PCORI-funded initiative designed to improve the nation’s capacity to conduct comparative clinical effectiveness research. More information about PCORnet can be found here.

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