2020 began with a surprise for many people, industries and governments. The coronavirus outbreak turned the world upside down and became a global threat the likes of which we hadn’t experienced for ages. Unfortunately, the clinical research industry was also impacted severely mostly due to the social distancing measures recommended by national and global organisations and the risk of people getting infected when visiting a hospital, interacting with study teams and other patients or travelling in public transport. This resulted in halting many recruitment activities in the countries until further notice and cancelling patient visits while clinical trials are on hold.
It didn’t take much time until the regulatory agencies issued guidance with regards to the conduct of clinical trials during the COVID-19 pandemic. This prompt action taken by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) was in direct response to global concerns around assuring the safety of clinical trial participants, maintaining compliance with good clinical practice (GCP) and minimizing risks to trial integrity during this unprecedented time.
These latest regulatory guidelines permit sites, sponsors and CROs to adjust their study operations to navigate the crisis during the pandemic, however, there are conditions that must be met in order for new solutions to be considered.
Guidelines go in three main directions which we have summarized below: ongoing trials, new trials, and COVID-19 related trials. In all three categories, the utmost mandate is:
Ensuring the health and safety of trial participants is paramount. Sponsors should consider each circumstance, focusing on the potential impact on the safety of trial participants, and modify study conduct accordingly. In all cases, it is critical that trial participants are kept informed of changes to the study and monitoring plans that could impact them.
Ongoing Clinical Trials
The US and European regulatory agencies both recognize that global pandemic and local circumstances may lead to a change in the benefit-risk ratio. Sponsors should consider doing their risk assessment whether the following measures could be appropriate in mitigating the influence of COVID-19 on their clinical trial protocols. Measures and their implementation should be agreed with investigators and could be:
- Conversion of physical visits into phone/video visits;
- Postponement or complete cancellation of visits to ensure that only strictly necessary visits are performed at sites;
- A temporary halt of the trial at some or all trial sites;
- Suspension or slowing down of recruitment of new trial participants;
- Extension of the duration of the trial;
- Postponement of trial initiation and/or activation of sites that have not yet been opened;
- Closing of sites without compromising the safety and well-being of patients already participating and data validity;
- If unavoidable (it should be justified that this is a truly exceptional situation based on the personal risk-benefit ratio for the individual trial participant), transfer of participants to investigational sites away from the risk zones or closer to their home, either to sites already participating, to new ones. Initiation of new trial sites is generally not expected in the current situation unless no other solution exists for the trial participant. If there is an urgent need to open a new trial site for critical trial visits, for example, outside the hospital, this may be implemented as an urgent safety measure (USM) and then submitted as a substantial amendment (SA) application for the approval and initiation of an additional trial site.
New Clinical Trials
Initiation of new trial sites is generally not recommended in the current situation. It is suggested that new clinical trial applications are postponed.
New Trials Aiming to Test New Treatments for COVID-19
There is a call for large, multinational trial protocols for the investigation of new treatments for COVID-19. In addition, sponsors are encouraged to consider the submission of such applications for an accelerated assessment when possible (e.g. VHP for EU) in order to avoid delays in reviews.
Sponsors are also recommended to prospectively contact the authorities and include COVID-19 in the subject of their submissions so that these are prioritized by authorities.
For the summary of all key highlights of EMA and FDA and how national regulators respond to them, download our detailed report.
What are countries doing?
In order to see how different countries worldwide are responding to the regulatory agencies’ recommendations and what their national action plan is, we deep-dived into the various national guidelines.
Countries like the USA, Japan, Germany, France, Spain, UK, Italy, Belgium, Netherlands, Australia, Bulgaria, Canada act similarly and follow the above recommendations. We observed the following agreements in their local regulatory guidelines:
- Countries’ authorities are giving COVID-19 related activities top priority.
- All require that COVID-19 is included in the subject line of all submissions related to it. Some authorities have even dedicated a phone line so that they are contacted prospectively for advice, consultations, discussion on Coronavirus issues.
- Standard review and approval timelines are not being amended; however, given the priority to COVID-19 related issues, delays are possible.
- New patients are not currently being recruited. Participants already in a trial are being taken care of in a way that their health and safety is guaranteed, while at the same time, local isolation requirements are met (e.g. remote visits are introduced, self-testing by patients, other).
If you are interested in the specific recommendations for certain regions and/or countries, make sure you download our report which includes key highlights of local guidelines in English.
Ensuring that your patients remain safe while still enrolled in your study is pivotal, and we’re committed to doing our part to help you meet your goals. Because #ClinicalResearchMustGoOn!