Around the Globe: Japan

Impact of COVID-19 on Clinical Trials & Research in Japan: Identifying Issues at Clinical Sites, Pharmaceutical Companies, and CROs

Hajime Saijo
DIA Japan

The first reported case of COVID-19 in Japan was confirmed on January 16, 2020. The number of cases increased steadily thereafter and by mid-March more than 1,000 cases had been reported. In early April, the infection rate began to increase rapidly with several hundred new cases confirmed daily. By April 17, more than 10,000 cases had been reported.

As the crisis evolved, clinical trials and research at medical institutions in Japan began to be greatly affected. In April and May, DIA Japan convened a series of online workshops that brought together industry, government, and academia to share the following insights.

Key Takeaways:

Different interpretations of risk caused by COVID-19 among sponsors have resulted in inconsistency in decisions to continue or suspend clinical trials in Japan.
Source data verification and monitoring are among the aspects of clinical trials most negatively impacted by COVID-19, but some of these impacts have been and may continue to be ameliorated by the growing application of remote and digital tools.
This pandemic has also highlighted the importance of crisis management strategies and skills that require further examination and improvement to ensure a better response to future crises.

Risk Perception Among Sponsors

The differences in risk perception among clinical sponsors during the COVID-19 crisis have been clear. Clinical trial monitors who have visited clinical sites seem to have had a low level of awareness regarding the risk of being infected, and even the risk that they themselves may spread the virus to clinical sites, during the COVID-19 crisis. With such different risk perception among sponsors, decisions to continue or to suspend clinical trials have been inconsistent. As a result, medical institutions have had difficulty managing clinical trials and clinical research during the crisis.

Challenges for SDV and IRBs

Challenges in conducting clinical trials during COVID-19 such as effective use of remote monitoring and Source Data Verification (SDV), Institutional Review Board (IRB) management, protocol deviations, investigational product supply, and continued use of paper-based documentation, have emerged in this pandemic.

Where facility visits are restricted by the Japanese government’s declaration of emergency, clinical monitors have been relying on digital means for remote monitoring and SDV. The number of medical institutions that can directly access electronic medical records is still limited; institutions that do not have such access must follow a time-intensive process of checking original documents online or by telephone. This lack of access to electronic medical records highlights the delay in healthcare digitalization and computerization, and industry’s continuing reliance on paper-based documentation, in Japan.

One panelist, a physician with an extensive knowledge of clinical trials, suggested that SDV may not actually be necessary because medical institutions can be trusted to proceed without it. A panelist from a pharmaceutical company concurred, noting that sponsors assess and select clinical sites through a thorough facility survey. It was clear from these discussions that further review of SDV in Japan is required.

Other panelists pointed out that in terms of IRB operations, the handling of deviations, and the delivery of investigational drugs, notifications from regulatory and other authorities have been issued in a timely manner according to relevant needs. A representative of PMDA also described how information on COVID-19 has been disseminated in Japan and overseas. Citing safety issues with anti-cancer drugs, another panelist stressed that the delivery of investigational drugs must be carefully planned and implemented to ensure patient safety.

Audience Polls and Responses

The audience were asked to respond to real-time polling questions throughout these webinars.

One question asked the audience whether they felt the countermeasures employed in response to COVID-19 could become standard practice in the future. In terms of IRB reviews carried out via eMail, 76% of attendees felt this countermeasure could become standard while 24% did not. In the ensuing discussion, some institutions favored eMail-based deliberations while others stressed the importance of gaining consensus through in-person or web-based meetings.

When asked who should decide whether to suspend or resume a clinical trial during a pandemic, 60% of the audience answered that it should be decided together by the investigator, the director of the facility, and the sponsor. During the COVID-19 pandemic, there have been instances of sponsors asking the clinical site IRB to determine whether new patients should be registered or the trial should be discontinued. There have also been instances in which sponsors made this decision themselves. This inconsistency has resulted in confusion that could have been avoided had the investigator, the facility director, and the sponsor all been involved in this decision.

Another panelist suggested that during emergencies such as COVID-19, we should return to fundamental concepts, guidance and law such as the Helsinki Declaration and the Medical Practitioners Act to ensure that risks can be appropriately evaluated and adequately managed at clinical sites.

The author and editor also wish to thank workshop chairs Hironobu Saito (Daiichi Sankyo Co. Ltd.), Eri Sekine (Novartis Pharma K.K.), and Atsushi Tsukamoto (Daiichi Sankyo Co. Ltd.).

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