The sheer scale and impact of the coronavirus pandemic has been unprecedented. So too has the response of pharmaceutical and life science companies, scientists, researchers and regulators. I have watched with optimism as insights have been shared, collaborations formed, and candidates accelerated into clinical trials in a bid to find an effective set of preventative and therapeutic tools to combat the virus.
Away from the focus of Covid-19, there are also thousands of clinical trials developing future treatments for other life threatening and debilitating diseases. The impact of lockdown measures and social distancing has challenged the continuity and integrity of these trials. Over 1,000 trials have been suspended or stopped as a result of Covid-19 but this is only a small subset of the 46,800 active trials currently listed on ClinicalTrials.gov.
What have those companies who have managed to maintain their clinical trials done so well?
These companies have crucially shown flexibility, decisive thinking and an openness to adopt innovative approaches in maintaining clinical trial continuity, as well as protecting patient safety. There are five areas where we are seeing trial Sponsors taking on these approaches.
Virtualising the trial
To facilitate patient visits and reduce pressure on a health system straining to tackle the pandemic, companies have looked to digital mechanisms.
Phone and video visits and the adoption of telemedicine platforms have been pursued by pharma companies to enable follow-ups on clinical measures and safety reporting. Where urgent changes to trial conduct have been made, digital re-consenting has been deployed. After many years debating this step, necessity has delivered a decision and confidence in a solution for the future.
Whilst in March, Johnson & Johnson (through their Janssen subsidiary) started a virtual trial in heart failure. The CHIEF-HF trial was launched 16 March as lockdowns began but still recruited 44 patients in the first week and is on track to recruit a total of 2,000 patients at a tenth of the cost and up to 50% faster than a traditional trial.
Virtualising trials is also something patient advocacy groups have proposed as a mechanism for improving patient recruitment and retention for clinical trials. The recruitment and retention of patients has historically been slow, expensive and unpredictable for sponsors, but developing a digital platform to enable the trial could be an opportunity for significant improvements in many disease areas, e.g. asthma, diabetes and haematological cancers.
These examples of virtual tools have allowed patients to start and continue taking part in these important trials from their home. When combined with direct to patient medicinal supply, they can deliver a fully virtual trial setup. This is a win for patients and pharma companies.
The impact of trial changes on patient experience, their wellbeing and the anxiety and emotional stress should not be dismissed lightly.
Whether it has been temporary halts, transfers to clinical sites away from Covid-19 facilities or closer to their home, for treatment administration or laboratory and diagnostic testing, the ability to communicate the required changes clearly with empathy and understanding, is paramount to keeping these patients participating. An integrated digital platform can provide this seamless engagement with the patient. For example, send an update on a visit location, offer online booking, detail the switch to virtual visits or capture an electronic clinical outcome assessment.
I recognise that many of the changes for patients have been necessitated due to the circumstances, but I would hope that a greater emphasis on an improved patient experience will remain high on the agenda for all companies in the post-Covid world. The modernisation of ICH E8 - General Considerations for Clinical Trials - ready for implementation in 2021 will strengthen this potential.
From the perspective of the trial Sponsors, they have had to alter how they deliver their oversight for trials.
Many Sponsors have suspended their routine monitoring visits at investigator sites and implemented changes to the mechanisms used for follow-up.
Remote monitoring and a higher proportion of centralised activities, e.g. data review, has enabled companies to meet their regulatory commitments and remain confident in the quality of their trials.
The investigator sites too have had to alter their on-site monitoring plans, again relying on the same remote and central activities to provide assurance of the quality and compliance of on-site clinical activities.
All changes to monitoring must be well documented in order to not constitute a serious breach.
Logistics of medicinal supply
We have all seen the disturbances to global supply chains caused by the pandemic and restrictions on people’s movement. This can present a fundamental risk for running trials as the supply of investigational medicine to trial participants must be continuous.
It is clear that strong business continuity plans and rapid decision making have enabled companies to extend supplies into investigator sites and utilise direct-to-patient delivery, which have been a key success factor in maintaining trial continuity. Putting in place appropriate processes to account for the use of Investigational Medicinal Product (IMP) and ensure patient adherence has closed the compliance loop.
As I stated at the beginning, the response of regulators in providing rapid and clear guidance to industry on the available options has been impressive.
This guidance does not lessen the burden faced by Sponsors in ensuring compliance of protocol amendments and deviations etc (many of these changes are being made in real time to maintain trial feasibility), but reconciling and documenting these into a timeline of approved decisions and trial changes has been key to maintaining integrity later down the line when seeking regulatory approval.
In summary, the flexibility, willingness to try innovative ideas and speed of decision making in response to this crisis is in stark contrast to the industry that has previously been extremely slow to change. From my perspective this response has been a silver lining to the pandemic, it forced the industry to try new routes and has proven that they work. As we move through (and hopefully out of) this crisis, I urge pharma companies to continue with, and even accelerate, the adoption of the innovative approaches we have seen used so successfully during the pandemic and remain open to new ideas. Patient engagement through digital channels and remote and more virtual elements embedded into clinical trials can be a catalyst for faster and lower cost drug development across all disease areas. The future could now feasibly mean we can get more treatments to patients at a reduced cost to society.
If you would like to talk to Baringa about how you can respond to the challenges of Covid-19 within your clinical development programmes, or how to best accelerate changes to your digital trial capabilities, please contact Chris Maxted or Kate Moss.
About the author:
Chris Maxted is a Director in Baringa’s Pharma and Lifesciences practice and is based out of our London office.