5 min read

February Pulse Check on Decentralized Clinical Trials: Entry Points to DCT’s

By David Swanger on Mar 2, 2021 11:43:35 AM

Throughout 2021 we’ll take a look at the latest developments in the realm of Decentralized Clinical Trials. Read this monthly roundup to discover the latest trends, insights, and modalities of decentralized clinical trials.

This past February, our blog focused on the various entry points involved in moving trials to a fully Decentralized Clinical Trial (DCT). Although our industry is gaining familiarity with this new approach to clinical development, several questions remain. One of the most important we find our customers asking is “Where do I start?”. 

In February we dug into a couple of key entry points. The first has to do with electronic clinical outcome assessments (eCOA’s). The second has to do with enabling the voice of the patient.

Before we look at our recap, let’s first define Decentralized Clinical Trials (DCT’s) for those who have found this blog as their entry point in education. DCTs differ from traditional clinical trials by bringing the trial to the patient through a combination of technologies (eConsent, eCOA, TeleVisits, Sensors & Wearables), mobile/local healthcare providers, and enabling the voice of the patient. Thus, there are a variety of modalities that can be used as an entry point in decentralizing a trial, whether through consent, outcomes reporting, or site visits. Regardless of the point of entry, the solution must be tailored in a flexible and modular manner to fit the unique needs of an indication, therapy, or patient population.

This past month we published two blogs on how to successfully operationalize eCOA’s.
 

Our own Dr. Ingrid Oakley-Girvan began the month by delving into:

 The Language of COA’s

In the blog, Dr. Oakley-Girvan dives into the four categories of Clinical Outcome Assessments spanning Patient Reported Outcomes (PRO), Performance Outcomes (PerfO), Clinician Reported Outcomes (ClinRO), and Observer Reported Outcomes (ObsRO). She also examines the suitability of each outcome assessment for decentralization and how each can be measured remotely through various technologies and processes.

Next, our own Dr. Reem Yunis took a deeper look into the most popular form of eCOAs, Electronic Patient Reported Outcomes (ePRO):

I Want To Tell You in My Own Words: Patient Reported Outcomes

In the blog, Dr. Yunis charts the path our industry has taken from paper based patient reported outcomes to electronic. Important factors she highlights for consideration in the blog include the modality and device type a PRO is presented on as well as the challenges presented in achieving compliance. Both are factors which are heavily influenced by patient engagement and compliance.

In February we also continued to expand how we can give voice to the patients and caregivers that are critical to DCT adoption.
 

Over the past year Medable has been expanding it’s Patient Advisory Council and this February we announced the following:

Medable Expands Patient Advisory Council to Drive Patient-Centered Improvements in Clinical Trials

Our four new PAC members include:

Sumaira Ahmed: a marketing director at Brigham & Women’s Hospital in Boston. Shortly after being diagnosed with sero-negative Neuromyelitis Optica Spectrum Disorder (NMOSD) in 2014, she founded The Sumaira Foundation to raise global awareness and find a cure for NMO. 

Gaurav Dave, MD: an Associate Professor of Medicine, Associate Director of the Center for Health Equity Research, and Director of Abacus Evaluation Consulting at the University of North Carolina at Chapel Hill. 

Allison Kalloo, MPH: a patient recruitment specialist and the founder of Clinical Ambassador, iParticipate and CliniVIVRE aimed at expanding minority access and impacting diversity, equity and inclusion in clinical research. 

Paul Kidwell: a Boston-based public relations and patient advocacy consultant, providing media relations and patient engagement support for biopharmaceutical companies, and a rare disease podcaster. 

Additionally, several of our PAC members made important contributions to expanding the voice of the patient this past February including:
 

Wither the Caregiver. Phama and Healthcare’s New Best Friend 

In this blog Mr. Kidwell highlights some of the unsung heroes of our healthcare system: caregivers. He shares his personal experience of being thrust into the role. Just as “nobody expects to get sick until they do, for caregivers, this sentiment is exactly the same. The role and its inherent demands are never part of a person’s thinking”

Our own Sumaira Ahmed was also featured on a podcast:

Illuminating NMO: The Power of the Patient Voice

During the podcast, Ms Ahmed shares her story around Neuromyelitis optica and how she started a foundation that's mission is to amplify NMO patient voices and raise money for researching a cure.

Finally, February marked Black History Month and with it two of our patient advocates commemorated the life and legacy of Henrietta Lacks:

Getting Her Say: The Immortal Legacy of Henrietta Lacks

Allison Kalloo and Sumaira Ahmed investigated the legacy of Henrietta Lacks through different prisms, one focused on her impact on medical research and the other on how betraying public trust can have far-reaching and longstanding implications that we will continue to confront for some time.

Giving voice to the patient perspective will be critical to the ongoing success of Decentralized Clinical Trials (DCT’s). And we at Medable are honored and humbled by the work members of the Patient Advisory Council do every day to make these voices heard. Doing so is critical to entering DCT’s with the right perspective. 

As February turns to March, we at Medable will continue to look forward to how we can continue to operationalize DCT’s and help patients, sites, CRO’s, and sponsors to realize the full benefits of this powerful new modality of clinical research. In March we’ll turn our attention to overcoming implementation and planning obstacles related to DCT’s. 

Next week on March 8th, Medable is proud to participate in a Reuters webinar that will highlight how to:
 

Overcome Perceived DCT and eCOA Adoption Hurdles

 

Topics: decentralized trials PAC eCOA
4 min read

I Want To Tell You In My Own Words: Patient Reported Outcomes

By Dr. Reem Yunis, PhD on Feb 25, 2021 1:17:09 PM

As patient's health and quality of life became an increasingly important component of treatment response, clinical outcome assessments, or COAs, became an important part of evaluating the safety and efficacy of medical products. In January we covered COAs and their use in general. This post will focus on patient reported outcomes (PROs).

What patients report directly about their health condition and disease symptoms (i.e., without the interpretation of a clinician) is very important and could influence the course and outcome of their treatment. In clinical trials, PROs can be utilized to determine the safety and efficacy of medical products. Because they are subjective in nature and are influenced by the patient’s perception of their own disease, PRO measures must be well defined and collected in a consistent and robust manner. Instruments intended to capture health outcomes directly from patients can be developed and validated with appropriate sample sizes and rigorous study design. Once tested in the population of interest, or multiple populations in some cases, and adequately validated according to scientific rigor, they can then be used alone or in combination with biomarkers in research studies or clinical trials.  PROs combined with biospecimens or digital biomarkers from connected devices can provide direct or indirect evidence not only for medical safety but also for efficacy in clinical trials in support of labeling claims.

The Road From Paper to Electronic Mode

The digital revolution wave extended how healthcare is captured and delivered. Clinical trial processes were no exception, and many remember the transition to EDC platforms to capture patient data in clinical trials. Naturally, paper-based health assessments rode the tide and electronic COA (eCOA) have become a mainstay in clinical trial operations.

The FDA encourages the use of electronic PROs (ePROs) whenever possible for the simple fact that paper PROs lack the timestamp and thus an inability to confirm when the data are entered by the patient. As we enable more remote clinical trial engagement, ePROs take on even greater significance.  However, there is much more to the migration of a PRO to an ePRO than simply making a digital copy. The transition must ensure that the patient responses are equivalent between paper and electronic formats. This is not a straight line as the equivalency may need to be tested in multiple populations and the extent of changes impact the work needed to switch to the electronic road.

According to the ISPOR task force guidance, when a paper PRO is delivered in a new modality such as in a mobile app and only minor modifications are needed (things like spacing, font, etc.) small groups of 5-10 patients may undergo cognitive debriefing and usability testing interviews. However, when more significant modifications are made to PROs (when digitizing them), the process of migration necessitates robust clinical study designs and statistical analyses. This guidance was published by the ISPOR task force in response to the release of the FDA guidance “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims” and is likely key to follow if pharma is to adopt these electronic measures in clinical trials knowing the FDA will require a certain level of rigor. The ISPOR task force indicates when moderate changes are made to a PRO, equivalency testing is required which subsequently turns into a full-fledged psychometric testing protocol when substantial changes are implemented. In a nutshell, equivalency is measured by comparing the psychometric properties of the data collected from the device to that from the paper, and under the psychometric testing. It is assumed that the substantial changes may render the ePRO as a new measure and thus should be subjected to the same original process of development and validation before this new ePRO can be utilized in clinical trials.

In all modification levels usability testing is required, which is completed in the target patient population where it examines the ability of the participants to use the device and software and complete the digital assessment as intended.

Factors to consider when optimizing and implementing ePROs are covered in a paper by Fleming and colleagues in the journal Therapeutic Innovation & Regulatory Science (2015). Among them is the modality and device type on which the ePRO is presented, that includes audio, computer, tablet, smartphone, touchscreen, keyboard and mouse. Although a meta-analysis of over 40 ePRO studies found that device type did not impact equivalency, it is still important to keep in mind user experience as a factor in compliance, accuracy and longitudinal data capture.

While site-based ePRO compliance is ensured by the clinical research team, capturing remote ePRO compliance is more challenging as it depends on the patient's engagement and adherence to the ePRO study protocol reporting schedule and requires continuous monitoring by the site. This adds a burden to an already overwhelmed research and clinical staff.

Alternative mechanisms to monitor patient engagement are needed. One possible solution is real time analysis of data and utilization of notification applications embedded in the ePRO delivery platform to help nudge and encourage action by patients.

When designed and developed appropriately with thoughtful implementation for engagement, patient-centered and clinically meaningful ePROs can make a significant difference in the approval of a new medical product and treatment.

References and Resources

Coons SJ, Gwaltney CJ, Hays RD, et al. Recommendations on Evidence Needed to Support Measurement Equivalence between Electronic and Paper-Based Patient-Reported Outcome (PRO) Measures: ISPOR ePRO Good Research Practices Task Force Report. 2009. Value in Health 12(4):419-429

Doward LC and McKenna SP. Defining Patient Reported Outcomes. 2004. Value in Health 7(1):S4-S8

Fleming S, Barsdorf AI, Howry C, et al. Optimizing electronic capture of clinical outcome assessment data in clinical trials: the case of patient-reported endpoints. 2015. Therapeutic Innovation & Regulatory Science 49:797–804

Food and Drug Administration. Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. 2009.

Powers JH, Patrick DL, Walton MK, et al. Clinician-Reported Outcome Assessments of Treatment Benefit: Report of the ISPOR Clinical Outcome Assessment Emerging Good Practices Task Force. 2017. Value in Health 20(1):2-14

Walton MK, Powers JH, Hobart J, et al. Clinical Outcome Assessments: Conceptual Foundation—Report of the ISPOR Clinical Outcomes Assessment – Emerging Good Practices for Outcomes Research Task Force. 2015. Value in Health 18(6):741-752

Weldring T and Smith SMS. Patient-Reported Outcomes (pROs) and patient-Reported Outcome Measures (pROMs). 2013. Health Services Insights 6:61–68

Topics: decentralized trials medable DCT eCOA ePRO
5 min read

January 2021 Pulse Check on Decentralized Clinical Trials: Looking back on 2020 and at What Lies Ahead in 2021

By David Swanger on Feb 5, 2021 11:10:12 AM

Throughout 2021 we’ll take a look at the latest developments in the realm of Decentralized Clinical Trials. Read this monthly roundup to discover the latest trends, insights, and modalities of decentralized clinical trials.

2020 was a pivotal year for those of us who work in clinical development. Covid-19 threw the ultimate curve ball to patients, investigators, CRA’s, and just about everyone else who contributes to ensuring that clinical trials are reliably executed. Suddenly the status quo of asking patients to visit a clinical site for the lion’s share of scheduled assessments was no longer tenable. And as a result our industry turned to Decentralized Clinical Trial (DCT) methodologies for both the continuity and rescue of existing studies as well as the design of new ones.

As we entered 2021 we’ve observed a subtle and important shift in the thinking of many of the stakeholders we interact with on a daily basis. Rather than asking “why” a DCT makes sense, individuals have moved beyond this, now asking “how” to implement one. 

Medable started the month by sharing lessons learned in how we successfully deployed DCT’s in 2020. We also started to look forward to how clinical trials could be reimagined with DCT’s serving as a new foundation. We covered these topics in depth at JPM’s Annual Healthcare conference by  leading five different sessions at the conference. You can view each of the sessions here:

The Digitalization of Clinical Trials

Michelle Longmire Founder and CEO,  Medable,  Maria Fotiu Executive VP of Decentralized Solutions, Syneos Health, Cathy Gao – VP, Sapphire Ventures, Juliet Moritz – COO, Illingworth Research - 

Hindsight is 2020: Lessons learned from DCTs and 2021 predictions

Alison Holland Head of Decentralized Trials, Medable and Craig Lipset Advisor & Founder, Clinical Innovation Partners 

Interview with Rasmus Hogreffe

VP Decentralized Clinical Trial Innovation at Medable 

 Rerouting: How Real-Time Patient Data Will Drive the Future of Healthcare Michelle Longmire with guests: Andy Coravos, CEO, Elektra Labs, Maria Fotiu, Executive VP of Decentralized Solutions, Syneos, Thomas Switzer, Digital Health Scientist, Genentech, Priyanka Agarwal, Director and Head of Digital Health, Myokardi

And finally, you can read VP of Decentralized Clinical Trial Innovation, Rasmus Hogreffe’s overall thoughts and reactions on this year’s JPM’s conference here, on his blog. 

In January of 2021 we also welcomed two important leaders to Team Medable:

Andrea Valente joined Medable as our new Chief Operating Officer to scale the global delivery of Medable Decentralized Clinical Trials. As research and patient care move from the controlled environment of the clinic to the home, focus on operational excellence is paramount. Valente is a proven expert in operationalizing patient technologies in clinical research. She played an early role driving adoption and scale of electronic Clinical Outcome Assessments (eCOAs), one of the first technology categories to interact directly with patients outside of clinical settings. She most recently led development and launch of Oracle’s public health platform to address COVID-19 pandemic response and vaccine trials in the U.S., UK and several developing nations. You can read more about Andrea joining Medable here. 

Parag Vaish joined Medable as our new Chief Product Officer to transform the clinical trial experience for patients and clinicians. As Medable continues to expand its product portfolio, Vaish brings valuable expertise creating products that are intuitive and enjoyable, removing friction from the user experience. During his tenure as head of digital product at Tesla, Vaish led a team of 43, dramatically changing how people buy the Tesla Model 3 through advance deposits, paperless transactions, and personalized home delivery. His team also built a payment system for in-car upgrades. At StubHub, Vaish and team led development of the award-winning StubHub mobile app, featuring a personalized, seamless experience that enabled users to buy tickets in just three taps. At Epocrates, Vaish evolved its mobile app from a 1.0 forms-based product to a modern 2.0 experience to help doctors minimize drug-to-drug interaction dangers. You can read more about Parag joining Medable here.

January 2021 also marked Martin Luther King day. And with this special day in mind, we partnered with Allison Kalloo of the Medable Patient Advisory council to explore the very real disparities in diversity and inclusion in clinical trials. 

Allison was kind enough to share her visceral experiences of growing up and coming of age in the healthcare field dating back to her mom’s experience as a participant in the Civil Rights Movement and her subsequent career as a virologist focused on infectious diseases. This shaped Allison’s experience and led to her becoming one of the foremost thinkers in how to improve Diversity and Inclusion in clinical development. 

You can read Allison’s posts and watch her video interview with Dr. Michelle Longmire here:

 

You Believe in Diversity, Equity and Inclusion? Okay. Show Us.

Blog from Medable PAC member Allison Kalloo

Fit for a King: Bending the Arc of Legacy Toward Action

Blog from Medable PAC member Allison Kalloo

Q&A With Medable PAC's Allison Kalloo On MLK Day 

Video interview with Michelle Longmire, Founder and CEO of Medable, and Medable PAC member Allison Kalloo

In the coming months Medable will be focusing on how to get started with a decentralized trial approach from both a strategic and operational perspective and then turn to looking at the benefits of launching a DCT platform that standardizes how systems, processes, people and data can come together in a predictable way to drive even greater efficiencies in this exciting new realm. 

Stay tuned!

Topics: decentralized trials remote trials PAC medable MLK eCOA
2 min read

The language of eCOAs

By Dr Ingrid Oakley-Girvan on Jan 28, 2021 2:41:06 PM

What do patient’s care about most and what do clinicians consider essential to assess regarding their patient’s health and wellbeing while participating in clinical trials? These are commonly referred to as clinical outcome assessments (COAs). 

The four categories of COA

In patient-centric clinical trials, COAs are essential to understand the impacts of a drug on certain endpoints, for example, whether it is improving or diminishing quality of life and everyday activities that matter to patients. The FDA, signaling the importance of COAs and the need to develop additional ones, has even created specific guidance and pathways for their development and validation.  

Fortunately, one of the lessons from COVID-19 is that we can be flexible and efficient and conduct a multitude of COAs remotely, or what we call eCOAs. No longer do patients need to come into the clinic for every assessment:

  • ClinROs can be measured over a televisit
  • PROs can be measured through patient directed surveys on a mobile app
  • ObsROs can be measured on mobile apps with care partners assistance at home
  • And device data can be used to generate PerfOs

Not only can we collect these at standard times as if patients were “in clinic” but we can collect them even more frequently adding critical new data to better assess health related quality of life impacts that patients often highly value. If the most important thing to a patient is being able to remain mobile, feel less foggy or fatigued, we can incorporate additional time points to better understand the effects of a trial medication or concomitant meds on outcomes and endpoints.

Furthermore, in many cases longitudinal data collection may be analyzed to monitor participants for simmering adverse events and provide early warning of declining health with which clinical teams can act quickly.

Technology enables this to now be done at scale in a modular fashion which not only helps protect patients but also prevents trial drop out and can encourage retention as patients may feel they are receiving better care.

There is a freedom created by these discoveries and solidification of approach. Patients are no longer tethered to a clinical site, this means patient travel burdens are reduced and distance is of diminishing importance when making a decision to participate or remain in a clinical trial. At the same time, in a decentralized clinical trial model, facilitating remote data capture that occurs at greater frequency in an easily scalable approach will enable statistical assessments that are reliable and allow for new COAs to be developed that can support labeling claims and improved patient health. In sum, the language of eCOAs is a win-win for pharma and patient health.

Learn more here: https://www.medable.com/products/ecoa-epro

Topics: decentralized trials Hybrid Trials TeleCOA clinical trials eCOA