How COVID-19 clinical trials are planned and what we can learn
Yesterday, the National Institute for Health Research (NIHR) announced that 30 hospitals across the UK are to trial 5 new drugs in the coming weeks. The compounds under the microscope have been disclosed for the first time, they include:
Heparin - a blood-thinning drug that has been shown to not only combat lung viruses by stopping the disease entering the cells, but also to act as an anti-inflammatory. The drug is also already widely-used in hospitals across the country, and so will be efficient if results can prove its effectiveness.
Zilucoplan - a potential treatment of myasthenia gravis, a skeleto-muscular disorder, developed by the Belgian biopharma company UCB. Zilucoplan is thought to help stabilize activity in the immune system that can kill cells and lead to potentially fatal lung and tissue damage.
Bemcentinib - developed by BerGenBio, a tablet used to treat blood disorders that has been shown to have a potent antiviral effect. It works to protect healthy cells from viruses such as Ebola and Sars by keeping the immunity created by type 1 interferon proteins active.
Calquence - currently used to treat lymphoma, a cancer of the immune system. The drug was chosen for a formal trial after anecdotal evidence revealed a significantly reduced incidence of complications from Covid infection or severe lung injuries.
Medi3506 - tackling skin disorders and trialed by AstraZeneca as a treatment for asthma, an anti-inflammatory injection that acts to control a phenomenon in the body targeting the immune system. As a result, the drug controls fever, inflammation, and fatigue all associated with the condition.
These trials mark another step forward for the industry that was, only months prior, at a complete standstill. It appears, with a boom in research at the moment, that clinical studies are truly back up and running, and so begs the question: how has such a dramatic change been possible in so little time?
The answer lies in how research everywhere has responded to, and is now successfully operating under, government guidance. In the US, while details published by the FDA makes clear that anything written in their March 2020 document is recommended and not required, how the industry has responded to this advice appears to have triggered current activity. According to Healthgrades COVID-19 Patient Confidence Study, that's results were published only last week, around 86% of patients surveyed are now comfortable visiting health care providers. Chief Medical Officer at Healthgrades, Brad Bowman, MD, has also gone on record to state his optimism for the industry in the coming months:
“As the country emerges from COVID-19, we’re watching consumer confidence shift back to where it was prior to the onset of this crisis.”
Today, we set out some of the key points of the guidance given by our top health regulators that are guaranteed to help any researcher restart or start-up their clinical trial. Whether you are finalizing the plans on your own study or interested in joining a clinical trial yourself, here are some of the guidelines that studies are now successfully implementing to ensure safety and security in a time of high external dangers.
First and foremost, it has been established that any changes in trial protocol typically are not implemented until they are presented to and approved by the Institutional Review Boards (IRBs) and the Independent Ethics Committees (IECs). Not all trials will need to implement alternative protocol as some studies already follow strict hygiene and social-distancing regulations, i.e. research and treatment for fatal or infectious diseases; but for those in our other areas, the need to put new processes in place or to modify existing processes will vary by the protocol and local situation.
As part of the recommended assessment that will determine if any changes need to be made, researchers should consider whether it is appropriate to delay some assessments for ongoing trials, or, if the study cannot be properly conducted under the existing protocol whether to stop ongoing recruitment, or even withdraw trial participants. A further recommendation considers the employment of third-party health care providers in carrying out daily COVID screenings. Lexology provides an excellent resource for researchers concerned about the intricate mechanisms of a procedure of this nature; check out their guide here.
Robust efforts by sponsors, investigators, and IRBs/IECs to maintain the safety of trial participants and study data integrity are expected, and all efforts should be documented. As stated in their report, the FDA recognizes that protocol modifications may be required, including unavoidable protocol deviations. Ultimately, efforts to minimize impacts on trial integrity, and to document the reasons for protocol deviations, is paramount to running research today.
While sponsors have always been influential over the running of a trial, the FDA’s report places more of an emphasis on stakeholders in ensuring the safety of trial operators and participants. The document states:
"Sponsors, in consultation with clinical investigators and IRB/IECs, may determine that the protection of a participant’s safety, welfare, and rights is best served by continuing a study participant in the trial as per the protocol or by discontinuing the administration or use of the investigational product or even participation in the trial. Such decisions will depend on specific circumstances, including the nature of the investigational product, the ability to conduct appropriate safety monitoring, the potential impact on the investigational product supply chain, and the nature of the disease under study in the trial.”
There is a real emphasis on the responsibility of the sponsor being pushed here, with companies now being urged to take a hands-on approach in organizing alternatives for safety assessments (e.g. phone contact, virtual visits, alternative location for assessments, including local labs or imaging centers) and additional safety monitoring for patients on withdrawal of an active investigational treatment. The result: patients can feel secure knowing that their safety is being monitored and constantly considered by a committed third party.
With all this change, it is important that how data is recorded is appropriately modified also. Changes in study visit schedules, missed visits, or patient discontinuations may lead to missing information. It’s important that companies capture specific information in the case report form that explains the basis of the missing data, including the relationship to COVID-19 for missing protocol-specified information (e.g., from missed study visits or study discontinuations due to COVID-19). This information, summarized in the clinical study report, will be helpful to the sponsor and FDA in determining the efficiency of the trial as a whole.
In addition, COVID-19 screening procedures that may be mandated by the health care system in which a clinical trial is being conducted do not need to be reported as an amendment to the protocol even if done during clinical study visits, unless the sponsor is incorporating the data collected as part of a new research objective. These guidelines are put in place to ensure maximum clarity on the presentation of trial data that, ultimately, determines the tested product's efficacy and safety in further studies and in potential public use.
Here at Citruslabs, we are dedicated to keeping you up-to-date on the latest clinical trial news and developments. As a company we have a wealth of experience in the field; with the success of our #1 health app, Mindmate, in 17 countries and a trial database with over 3 million patients on record. Not only this, we are proud to offer all COVID-19 clinical trials free access to our patient-recruitment dashboard.
Interested in finding out more? Get in touch with one of our team here, and check out our archives for all our top tips and tricks on running a successful clinical trial in today's constantly changing industry.