Early phase oncology trials: Pandemic-shaped protocols
The global pandemic has made its presence felt in the world of clinical trials, not least in Phase 1 oncology trials. Vanessa Dekou, Managing Director at CSI, offers her perspective on how COVID-19 is shaping future protocols and challenging conventional wisdom.
Patients in self-isolation or quarantine, relocated hospital staff and reduced trial site access are just some of the complications currently facing sponsors of both ongoing and new clinical trials. The need to adapt and innovate quickly has become the top priority and the EMA,1 MHRA2 and FDA,3 along with many other regulatory agencies, have released specific COVID-related guidance to steer sponsors through the complexities and deviations from the protocol. The temporary changes that have enabled these trials to continue through the pandemic have revealed areas for improvement and may well establish themselves as the default in protocols in the months and years to come.
Patient safety remains of paramount importance, and the obvious first consideration is ‘whether [a patient’s] net clinical benefit (clinical benefit minus toxicity) [is] sufficient to expose them to the risk of contracting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) while on an investigational medicinal product (IMP)’.4 The vast majority of cancer patients are immunocompromised and many trial sites are located in urban centres where there are typically higher infection rates. The pandemic has turned a routine hospital visit into a potentially life-threatening outing, raising concerns about the ability to truly separate cancer patients from the other trial site areas where COVID-19 is being treated.
The centrality of patient safety has naturally led to remote monitoring, video calls over in-person consultations, and increased digitisation – the process of converting information from a physical format into a digital one – in clinical trials. The pandemic has forced many companies, including our own, to adopt remote working by default, challenging assumptions about how things must be done and accelerating the adoption of new technologies and ways of working. It is inevitable that wet-ink signatures for trial documents will be replaced by digital alternatives – a much-needed change! There are also discussions around ways that increasing digitisation in the sector can streamline the clinical trial process and deliver higher efficiency. For example, ‘duplicate requests by different sponsors for investigator credentials, site feasibility, and declaration of conflicts may be circumvented using an open online database containing accessible information for all’.5
[If we retain and implement all the recent adaptations, it is possible that we may prefer the ‘new normal’ of clinical trials for both patients and clinical trial sponsors.]
We proposed in our previous blog post that direct to patient trials [link] are likely to be on the rise in the future and, in its most recent COVID-19 guidance, the MHRA recommended the following: ‘If a trial participant cannot attend a trial site, then delivery of IMP to a participant’s home is acceptable and no substantial amendment notification to the MHRA will be required. This applies to supply from the trial site or directly from the sponsor’.2 It’s possible that these guidelines will merely accelerate the adoption of direct-to-patient trials to the point where they become common place. The pandemic has also raised questions about the necessity and frequency of in-person contact, and ‘dosing schedules of cancer drugs have been modified where acceptable, and oral treatments, where available, have been leveraged to limit hospital visits. Administration of treatment in local satellite centers [sic] has also been explored, as well as the feasibility of local or even home-based blood draw services and treatment infusions’.
Towards a better future
The pandemic has challenged the notion of what is essential to the clinical trials process, from recruitment procedures through to dosage frequencies. While we shouldn’t look to put a positive spin on the long-term health impact of many oncology trials being delayed or put on hold, the best outcome for the sector is to ensure that we learn and improve in response to this crisis. The pandemic has created the impetus to question unchallenged conventions – such as the exclusion of certain patient populations from immune-oncology trials – and reflect critically on best practice. A recent Cancer Research UK blog cites Stephen Nabarro, Head of Clinical Operations and Data Management, as commenting: “It is important that we find a positive legacy from this difficult time… And one that will come, or we’re certainly hoping will, is a shift in our trials becoming more patient-centric. So much of what we do has historically been focussed around the idea that patients must go into the clinic regularly.”6
It’s hard to predict the future, but we can be sure that it will be a future shaped by the pandemic and hopefully for the better. If we retain and implement all the recent adaptations, it is possible that we may prefer the ‘new normal’ of clinical trials for both patients and clinical trial sponsors. If nothing else, that is an outcome worth aiming for.
We are excited to support you in your ongoing or future oncology trials, whether its updating or developing a protocol, or finding flexible comparator sourcing solutions. CSI delivers medicines on a global scale consistently and with care, and we want to be your next clinical trial supply partner.
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It would be great to catch up with you virtually