n February 6th, representatives from across the healthcare industry came to Bethesda, Maryland, to attend the 10th Anniversary Symposium of the Clinical Trials Transformation Initiative (CTTI). Speakers and panelists from industry, patient organizations, academia, the US Food and Drug Administration (FDA), and others discussed examples of how CTTI practices have been successfully adopted, their broader impact on the regulatory environment, and the future of clinical trials. Here are some key takeaways:

• CTTI has overcome inefficiencies in the clinical trial system by bringing together key stakeholders to address critical issues impacting clinical development collaboratively.
• Incorporating CTTI’s Quality by Design (QbD) principles has allowed study teams to reduce the volume of data collected during study visits and to implement strategies to help patients complete electronic diaries that provided critical data for study evaluation.
• With its Patient Groups and Clinical Trial Project, CTTI has demonstrated that meaningful patient engagement can enrich research and drive improvements in clinical care. Part of CTTI’s ongoing work is to develop a tool to identify high-value engagement opportunities.
• CTTI’s Central Institutional Review Board (IRB) Recommendations have helped organizations implement a single IRB of Record by providing tools and templates that speed implementation while maintaining proper ethical oversight of a study. Template agreements to operationalize a single IRB are now among the wealth of tools available to researchers, sponsors, and IRBs.

Looking Back and Moving Forward

In his reflections on the partnership’s impact over the past decade, former FDA Commissioner and CTTI Co-Founder Robert Califf described how CTTI had originated out of a shared concern about the substantial inefficiencies in the clinical trial system. Success in combatting these challenges hinged on bringing together all key stakeholders, including patients, to work together on the various critical issues that impact clinical development.

Including patients as full partners on CTTI’s steering committee and projects has provided an important and increasingly appreciated perspective on the many topics that the partnership has addressed in the past decade, including quality by design, trial recruitment, and electronic health data. CTTI continues to influence how patients are engaged, most recently through supporting FDA’s Patient Engagement Collaborative (PEC), which brings together members of the patient community to discuss best ways for patients to participate in the FDA’s regulatory discussions about medical products.

Much of CTTI’s 10th Anniversary celebration reviewed CTTI’s impact on the clinical trial enterprise through projects like Quality by Design, Patient Groups and Clinical Trials, and Single Institutional Review Board (IRB) of Record. But participants also discussed CTTI’s potential future role in developing models for robust evidence generation in an age of big data, artificial intelligence, and transparency.

External trends, in particular, could upend drug development, including a “home inversion” in which data collection sites are shifted from hospitals to the homes of patients. Patients and healthcare systems are increasingly aligning to produce needed evidence, and the growing co-mingling of biomedical, clinical, behavioral, and biological data may provide better predictive value than traditional trials. Project Baseline, for example, maps human health in real time, similar to online navigation systems that provide drivers with real-time navigational data based on streets maps.

The final panel discussed the future of clinical trials, touching on topics like positive publication bias and the importance of negative results, data sharing barriers, guidelines for measuring value, and the need for more innovative trial platforms and flexible designs in rare diseases. Panelists pointed out that some therapeutic areas are advancing clinical trial improvements more rapidly than others, showing greater flexibility and translatability, and that real-world evidence won’t be the magic bullet solving everything, especially with a fragmented healthcare industry complicating data collection.

As the day closed, the consensus was that CTTI, as a public-private partnership, is uniquely positioned to build upon its decade-long success to help shape the clinical trials of the future. Executive Director Pamela Tenaerts encouraged others to share their experiences with CTTI recommendations to contribute to its databank of case studies and inform the clinical trial enterprise.

Project Examples

Quality by Design (QbD)

The featured QbD project provided symposium attendees with a model for proactively building quality into trial design. Implemented by a range of industry, academic, and other non-profit organizations, the model streamlines trial execution and focuses trial oversight on preventing “errors that matter.”

The project’s recommendations have shown to reduce complexity and burden on patients, ensuring that finite resources are funneled into activities that significantly impact study outcomes. It was pointed out that encouraging trial sponsors to compare trial design and oversight “before and after” applying the QbD principles may be one means of demonstrating the effectiveness of this approach. This would also alleviate concerns that trial complexity and cost may discourage study conduct, leading to fewer important questions being answered.

Incorporating CTTI’s Quality by Design (QbD) principles into the design of a phase 2 study at Amgen, has allowed the study team to reduce the volume of data collected during study visits and to implement strategies to help patients complete electronic diaries that provided critical data for study evaluation.

Patient Groups and Clinical Trials

Over the past 10 years, CTTI has truly transformed patient involvement in research and development. With its Patient Groups and Clinical Trials project, CTTI demonstrated that meaningful patient engagement can enrich research and drive tangible improvements in clinical care by de-risking early stage development efforts and enabling more effective and efficient trial designs. In fact, involving patients early has been critical in the success of the Friedrich’s Ataxia Research Alliance, a case study featured in the symposium.

CTTI has recommendations and tools for patient groups, sponsors, and other involved stakeholders to ensure that research organizations better leverage the wealth of patient expertise. Since the unique value of patient engagement can also be measured in terms of financial impact for an organization, CTTI is currently developing a tool to identify high-value engagement opportunities.

Single Institutional Review Board (IRB) of Record

Supported by strong evidence of its efficiencies, CTTI recommends the use of a Single IRB of Record for multi-centered trials. In fact, there’s no compelling evidence suggesting that using multiple IRBs reviewing a protocol provides better ethical oversight than to use just one. Any appropriately convened IRB could serve as a single IRB of Record for all sites involved in a trial.

The featured case study exemplified how CTTI’s Central IRB Recommendations have helped organizations implement a single IRB of Record by providing tools and templates for researchers, sponsors, and IRBs to speed implementation while maintaining proper ethical oversight. Template agreements to operationalize a single IRB are now among the wealth of tools provided by CTTI.

In November 2007, the U.S. Food and Drug Administration (FDA) and Duke University co-founded a public-private partnership, the Clinical Trials Transformation Initiative (CTTI), to identify practices that increase the quality and efficiency of clinical trials. Today, CTTI’s mission goes beyond simply identifying practices; it now delivers and drives such practices with recommendations and tools to expedite adoption.