Clinical News Roundup: China To Accept Foreign Clinical Trial Data
By Ed Miseta, Chief Editor, Clinical Leader
In a move likely to benefit Chinese citizens as well as foreign drug firms, the Chinese government has agreed to accept data from clinical trials conducted outside China for the approval of new drugs. “Applicants can directly apply for drug listing registration after the completion of the international multicenter drug clinical trials,” the China Food & Drug Administration (CFDA) disclosed in a statement.
Until now, China only approved drugs that had been tested on participants in China, and foreign firms could start testing in China only after they had demonstrated the safety of their drug with tests conducted overseas. This meant that Chinese people gained access to innovative new drugs years after they had been approved overseas. In the past, many major drug companies did not bother to launch their drugs in China because of the cost and delay involved. By the time foreign-developed drugs gained approval, competing versions were often already available from Chinese firms.
CFDA has been reforming its drug registration process for several years. The agency earlier hired more reviewers to reduce its drug approval backlog. It also warned companies registering drugs in China to withdraw their applications—or face administrative sanctions—if they had doubts about the authenticity of their clinical trial data. The warning helped to reduce the number of applications that the agency had to review.
Janssen Establishes Mobile Medication And Data Management Technology Platform
Janssen Research & Development announced it has established the Integrated Smart Trial & Engagement Platform (iSTEP), an information technology toolset developed to automate investigational product supply and data management in clinical trials. The approach is available for industry-use and is designed to replace the paper-based conventional processes of managing clinical supplies and tracking patient health data with a cohesive suite of digital technologies.
iSTEP is a platform that leverages mobile technology, “smart” packaging, and electronic labels in an effort to streamline and automate the investigational product management process in clinical trials. Smartphone apps are integrated to support patients in following their treatment schedule and interacting with their healthcare provider while participating in a clinical trial. iSTEP is designed to capture and deliver real-time, adherence-related data for patient and sponsor insight with the goal of eliminating paperwork and improving processes for all parties.
“As clinical trials grow in complexity, duration, and cost, we are adopting different technologies to optimize workflow, improve communication, and expedite data reporting, all critical success factors in clinical trials,” said Andreas Koester, VP, R&D Operations Innovation at Janssen. “The open innovation philosophy at Janssen led us to develop iSTEP in a way that allows the technology to be available to other pharmaceutical companies. We believe that having a consistent approach across the industry can accelerate the process of bringing medicines to patients.”
The iSTEP platform consists of four modular components, each designed to be used separately or together as an end-to-end solution:
• eTracking uses scanners to verify and register all medication kit activities at the study site, including receipt, dispense, and return of kits. The design allows information to become immediately available to physicians and the study sponsor via a web portal, in an effort to eliminate paper documents and manual data entry and to reduce dispensing errors.
• eCommunication provides information that can be tailored to patient needs, such as reminders, dosing instructions and tutorial videos via their smartphone to encourage medication adherence. It also is designed to collect certain data, such as adverse events.
• eLabel augments complex, multi-language booklets that are customarily distributed in clinical trials, with an electronic drug label, supplemented with other patient-specific data, in the patient’s native language. eLabel’s flexibility is conducive to adaptive trial designs, as updates to the protocol can be made after the trial has been initiated and efficiently communicated to patients.
• eAdherence includes smart medication blister packs that register each pill as it is removed, to help track medication adherence. Continuous monitoring of medication adherence may enable real-time intervention.
Janssen has conducted a technical pilot with iSTEP and is working with health authorities and ethics committees to implement a pilot assessment of iSTEP within a clinical trial by the end of 2017. Going forward, Janssen plans to progressively implement iSTEP into a variety of clinical trials in its portfolio.
FDA Holds First Patient Engagement Advisory Committee Meeting
The FDA Patient Engagement Advisory Committee (PEAC) met for the first time to give the agency input from patients on clinical trials for medical devices. The meeting, held the week of October 9, 2017, focused on a number of key issues related to clinical trials, with the goal of increasing patient input on trial design, patient recruitment/enrollment/retention, and communicating results back to patients.
FDA announced the creation of the PEAC in September 2015 as part of a broader effort under the 2012 FDA Safety and Innovation Act to bring patient perspectives to regulatory discussions. The agency also agreed to further advance the use of patient preference information (PPI) and patient reported outcomes (PROs) in its commitments under the recently reauthorized Medical Device User Fee Amendments (MDUFA IV).
At the meeting, Center for Devices and Radiological Health (CDRH) Director Jeffrey Shuren said the agency will be better equipped going forward in its patient engagement efforts as a result of MDUFA IV. "We're now—for the first time—getting resources to build out a patient engagement group at CDRH. Prior to that, believe it or not, there were never dollars that had been allocated to us specifically for this kind of work," Shuren said.
FDA recently indicated that it is interested in creating a new Office of Patient Affairs to better support and coordinate patient engagement activities across the agency. With these efforts, and the development of guidance documents on PROs and PPI, Shuren said the agency has witnessed a major increase in the number of submissions that include patient-focused data.
"Over a five-year period, we saw an over 500% increase in the number of pivotal clinical trials for [premarket approval applications] PMAs that used patient reported outcomes, and now over 50% of our PMAs include patient reported outcome data," Shuren said.
CTTI Issues Sponsor Recommendations To Halt Investigator Exodus
Patient recruitment in clinical trials is difficult for most sponsor companies, but getting qualified investigators involved with trials is also a challenge. Most physicians will never take part in clinical trials, and many of those that do serve as an investigator will never do so again. To alleviate this problem, the Clinical Trials Transformation Initiative (CTTI) has issued a set of recommendations for the industry. Some relate directly to sponsor companies.
First, CTTI recommends that sponsors recognize investigators and research coordinators as key contributors to product development. This may include approaches such as thanking site staff personally or recognizing contributions of site staff and study participants via websites, television ads, publications, or presentations. When appropriate, site investigators should also be offered the opportunity to participate as co-authors on publications.
Second, sponsors should provide opportunities for investigators and site staff to remain engaged between trials. Inactivity between trials presents both challenges and opportunities. Sponsors, CROs, and health systems/private practices should actively support investigators and site staff between trials by providing developmental opportunities via attendance at clinical trial-related conferences, continual medical education certified trainings, and engagement with professional society and trade associations.
Additionally, sponsors are encouraged to create enrollable study protocols and follow FDA safety reporting requirements. According to the CTTI Quality by Design and Recruitment Project recommendations, attention to minimizing recruitment challenges at the trial design and protocol development stages is essential. This can be achieved by engaging all stakeholders as equal partners in the process, ensuring the relevance of the scientific question to stakeholders, limiting protocol complexity to reduce the burden of participation, developing realistic eligibility criteria, and limiting collection of data to only those needed to maintain patient safety and answer scientific questions.
The FDA’s requirements for reporting safety issues and adverse events impose critically important obligations, as well as burdens, on site investigators. Creating, reviewing, and dispatching adverse event (AE) reports can require significant time and effort, despite FDA efforts to minimize sponsor and site burdens in this area. Following referenced federal guidance and CTTI recommendations will lessen associated regulatory safety reporting workload.