By Deborah Borfitz

July 24, 2019 | The nonprofit collaborative TransCelerate BioPharma is making strides on multiple fronts to improve site-sponsor relationships and the clinical trial experience. It has even designed a Clinical Registry of the Future (RotF)—with and for patients—in hopes of influencing change to government-sponsored registries that many have found confusing and unfriendly.

TransCelerate-related initiatives were the subject of no fewer than five presentations made by industry leaders at the 10th Annual Summit for Clinical Ops Executives (SCOPE) in February. Jeneen Donadeo, program director of TransCelerate's patient portfolio, and Denise Reyes, director of its value and implementation portfolio, recently spoke to Clinical Research News to provide the latest updates.

Investigator Registry

Fourteen of 20 member companies now participate in TransCelerate's Investigator Registry (IR) via a data-sharing agreement that benefits both sites and sponsors, says Reyes. "By participating in the registry, sites increase their visibility to participating sponsors for potential site selection."

Editor's Note: Several TransCelerate speakers will be presenting at SCOPE Europe in Barcelona in September. Speakers will be covering the Investigator Registry and several other TransCelerate initiatives.

The IR gives sponsors five fields of objective, site-level data, says Reyes. Other site profile information is blinded, aggregated, and summarized as country-level statistics. Site details include equipment and training, and sponsors can run queries based on factors such as therapeutic area, indication, and location. "Member companies can also share site enrollment data, including statistics on how many patients were recruited for prior trials and how long recruitment took," she adds.

Profile data on investigators is available only if they consent to sharing the information through the IR or TransCelerate's site-facing Shared Investigator Platform (SIP), says Reyes. If consent is not obtained, only sponsors already working with those investigators would have those details.

Shared Investigator Platform

The Shared Investigator Platform is designed to reduce the administrative burden of trial execution for sites, says Reyes. During a single sign-on session, investigators can work with multiple sponsors and, potentially, their systems. Sponsors are working with vendors (e.g., electronic data capture, laboratory, interactive web response system) to allow seamless pass-through to all the systems sites would need to execute a trial, she explains.

The SIP "provides a unified homepage and dashboard of trial activities across all participating studies and allows users a central place to manage key information," Reyes continues. User and facility profile information are entered once and shared across participating sponsors. The information is owned and maintained by the sites and, whenever possible, reused across participating sponsors (e.g., curriculum vitae, study site information, Form FDA 1572-Statement of Investigator) to reduce rework.

Sites can, for example, upload GCP training certificates to potentially avoid additional, redundant training, Reyes says. Information from the facility profile also now replaces common questions on site feasibility surveys about site equipment, such as the availability of an EKG machine or ultra-low-temperature freezer. Feasibility questionnaires are therefore being shortened to include only protocol-specific questions.

"With the unified dashboard, surveys are electronic and become part of a task/notification workflow," notes Reyes. Emails are automatically generated when surveys are assigned, to remind sites when they're due and to inform sponsors once they've been completed. Some companies have reported a 50% reduction in survey response time, she says.

The SIP's functionality continues to expand. For the last release, Cognizant developed an open public API for investigator payments that works no matter what system a sponsor may be using. "This is a core aspect of the platform," says Reyes, "to be an open, interoperable platform to allow for flexibility and scale of functionality."

Although the SIP and IR work together, sponsors can elect to use the IR without participating in the SIP, says Reyes. "As investigators join the SIP, they are presented with a consent that unlocks data sharing within both the SIP and IR, allowing them access to the benefits of both systems." Profile information in the SIP is "de-duplicated and mastered" with the IR. "This is a one-way push as part of master data management activities," she says. "In addition, the combined solution opens for broader industry adoption in 2019."

Campaign Lessons

For much of last year, TransCelerate had a "One Person Closer" campaign actively underway to raise awareness about the value and need for clinical trials among healthcare professionals (HCP)—and to "better understand their attitudes about barriers to participation," says Donadeo. "The initial goals of the campaign were focused on sentiment change."

The campaign began by raising awareness through social media channels using video-recorded interviews with patients, researchers, and physicians about their personal experiences with clinical trials, Donadeo says. A dedicated Facebook and Twitter presence, and online polls conducted by SERMO, also provided insights from HCPs.

"What has been learned from the campaign is invaluable," Donadeo says. This includes "a significant need for ongoing awareness and educational programs to help HCPs access clinical trial information and effectively engage and inform their patients about trials from which they could benefit." TransCelerate has a work group devoted to helping HCPs "engage in more frequent and… fulfilling conversations with patients" toward that end.

Registry of the Future

The Clinical Research Access & Information Exchange initiative is another way TransCelerate aims to facilitate "improved touchpoints" for understanding and exploring clinical trial opportunities, Donadeo says. Materials and tools are being developed for patients, caregivers, and HCPs, and a mock-up of the more patient-friendly Clinical Registry of the Future has been shared with the National Institutes of Health (NIH) and other government agencies and nonprofit organizations.

Videos and the vision proposal are available on the TransCelerate website. Key envisioned functionality includes the ability for users to bookmark trials, as well as make and retain personal notes about them, and a visual indicator of new trials that have posted since their last search.

While the NIH continues to make improvements to the usability of clinicaltrials.gov, Donadeo says, "there are additional improvements highlighted in the RotF concept that we hope will be part of future releases." One condition is that industry first "resolve the data quality problem with registry submissions," she adds, so TransCelerate is now undertaking development of a clinical registry data packet.

A central feature of the packet is a self-scoring tool that sponsors can use to ensure they're submitting complete, consistent, timely, and plain-language data to clinical trial registries. Donadeo adds that TransCelerate also published a pair of position papers two years ago, one on the rationale for providing site contact information directly on trial registries and another making the case for improving information exchange with trial participants.

Additionally, three communication templates were developed for use by sponsors when communicating with patients throughout the clinical trial process: a thank you letter for when they join the trial, another for when they've completed it and a post-trial letter providing individual summary results.

Data Quality

In response to the growing demand for qualified and skilled individuals to serve on clinical trial data monitoring committees (DMCs), another TransCelerate work group is developing the concept of a publicly available DMC Registry, says Donadeo. It would provide a central repository of relevant data on clinical research professionals who wish to take on this role, including "whether they previously served as a DMC member or are interested in doing so but lack prior DMC experience."

The initiative is also developing an "apprenticeship model" for enhancing the skill set of DMC members to nurture their effectiveness in the role, Donadeo adds. "The proposed concept would focus on fostering relationships via mentor-mentee networks."

Separately, as part of its Interpretation of Guidances and Regulations initiative, TransCelerate looks to improve the quality of clinical research through the implementation of quality tolerance limits "in a way that facilitates compliance, efficiency and minimizes confusion and duplication of effort," says Donadeo. The objective is to meet the intent of "ambiguous regulations/guidances and operational expectations around the world" per ICH E6 R2.

Tackling Protocol Deviations

Protocol deviations are an industry-wide problem and TransCelerate has a team that has initiated discussions with the US Food and Drug Administration (FDA) and will be relying on the agency's guidance and expertise to develop a protocol deviation toolkit, says Donadeo. Lack of clarity regarding the definition of "important" protocol deviations has negatively impacted the ability to plan, collect, analyze, and report them.

Initial conversations with the FDA will seek to validate identified problems and the impact of protocol deviation management for stakeholders, Donadeo says. The team will also obtain feedback on proposed classification of "important" protocol deviations and recommendations for further stakeholder engagement strategies.

Over- and under-interpretation of important protocol deviations can delay the identification of important patient safety information, as well as influence the reliability of trial results and human subject protections, she continues. The objectives of the initiative are to "reduce the noise" and increase process efficiencies by improving interpretation of guidelines and management of protocol deviation processes.

Among the principles steering efforts of the initiative team:

• Build on definition of "protocol deviation" in ICH E3 Q&A R1
• The event occurred (i.e., not theoretical) and related to a data point or process identified in the protocol or documents referenced in the protocol
• Protocol deviations are independent of fault, blame, or circumstance
• Incorporate ICH E6 R2 into proposed definition of "important protocol deviations"
• Important protocol deviations are a subset of protocol deviations and may significantly impact "key or critical" study data

New Patient Engagement Toolkits

TransCelerate has several new projects underway to help sponsors better engage patients in the design and execution of clinical studies, says Donadeo, which can potentially improve participants' experience with and interest in enrolling in trials. Their involvement on the front end might also reduce protocol amendments and study participant dropout rates, and support development of more "fit-for-patient" drugs.

This month, TransCelerate will introduce a Patient Protocol Engagement Toolkit (P-PET) providing tools and resources to engage patients during the study design phase—as early as protocol concept—to create more patient-centric clinical trials, she says. P-PET includes a sponsor-facing operational user guide with case studies, a resource guide with sample questions and visual aids, and communication templates to use with patient advisory boards during the study design process.

TransCelerate will also be releasing a Study Participant Feedback Questionnaire (SPFQ) Toolkit, a key feature being a set of questionnaires given to patients at the beginning, during, and end of a clinical study. Sponsors can use their real-time feedback to reduce burdens of participation in future studies, says Donadeo. The SPFQ Toolkit, "inspired by patients and developed with patient input," includes a socialization deck for initial sponsor discussions and a sponsor-facing operational user guide, in addition to the three questionnaires.

The toolkit will leverage aggregated SPFQ data across a given sponsor's studies to inform actions to improve trials, Donadeo says. Both the SPFQ Toolkit and P-PET are expected to contribute to an improved partnership between sponsors and patients in clinical studies.