An article in Infection in July 2024 summarises discussions held at a VACCELERATE Consortium workshop, which explored the applicability of adaptive platform trial (APT) methodology in vaccine trials for both non-pandemic and pandemic conditions. The authors suggest that an “ever-warm” APT could be “ideally suited to improve efficiency and speed” in vaccine research. The paper is particularly pertinent as APT methodology has not yet been “widely adopted” in vaccine clinical research.
VACCELERATE and the workshop
In 2021 the VACCELERATE Consortium was established as an “integral” element of the EU’s response to the COVID-19 pandemic. Led by University Hospital Cologne, the network provides a “research infrastructure for vaccine trials” and includes 31 national partners in 18 EU Member States and 5 countries associated with the EU Horizon 2020 research programme.
Earlier this year, University Hospital Cologne organised the VACCELERATE APT Workshop as a way of “aligning” APT stakeholders. It hosted attendees from a “wide range of disciplines and backgrounds” with the aim of understanding the potential that APT has for pandemic preparedness. The resulting paper reflects “core aspects” discussions that took place, including a call for a “paradigm shift” from the “traditional” two-arm randomised clinical trial (RCT) to a “continuously learning adaptive platform trial”.
APT
Platform trials can be considered “disease focussed” and offer flexibility and the potential to “speed up” the evaluation of products through the shared use of infrastructure. Furthermore, the standardised framework of a platform trail facilitates comparisons between arms and increases statistical efficiency through shared common control data.
“In the context of vaccine development, in both an interpandemic and pandemic context, platform technology needs to be tailored to the specifics of an infectious disease affecting potentially large populations, against the background of rapid evolution of both the mutating virus and the development of natural and vaccine-induced immunity.”
The authors state that an APT framework that is tailored to the specific context of infectious disease vaccine development is “ideally suited to improve efficiency and speed” of evaluation. An APT offers the “continual ability to learn and benefit” as data emerge, but “thorough” planning is required on adaptions based on beneficial data.
“An APT builds on the well-known features of “traditional” RCTs, in particular experimentation, randomisation, and blinding. In addition, an APT offers the flexibility of adaptation rules and the integration of information from other relevant data sources, such as sentinel surveys and other epidemiological studies.”
Various data can be integrated for “valuable enhancement” and mathematical modelling and health economics expertise will support the design, dynamic adaptation, and assessment of vaccination benefits.
Vaccine APTs should collect a “variety” of clinical endpoints and combine endpoints to “gauge efficacy”. Indeed, the choice of primary endpoint might “shift over time’. Alongside endpoints, markers should be collected for potential validation as correlates of protection, and both “classical – marginal – vaccine efficacy” and “conditional” vaccine efficacy will be relevant. Each development must take place in “continual dialogue” with regulators.
Transparency and co-creation between researchers and health authorities are emphasised. Furthermore, the authors suggest that the “complexity and flexibility” of a vaccine APT will demand “additional dedicated governing bodies”.
Pandemic and interpandemic context
“There is consensus that a vaccine APT set up in the context of pandemic preparedness should run perpetually, i.e, “ever-warm” or “warm-base” in the interpandemic interval, and have the built-in ability to pivot to pandemic mode at shortest notice.”
When not in a pandemic situation, a vaccine APT should be “constantly fed” relevant research questions to create an “uninterrupted flow of new evidence”. These will likely come from research gaps in industry trials and result in informed public health decision-making. Interpandemic vaccine APT trial activity should focus on pathogens causing acute respiratory infection (ARI), such as RSV, SARS-CoV-2, or avian influenza.
Investigations will “preferentially focus” on the most vulnerable populations, which are underrepresented in industry trials, but this does not preclude the enrolment of healthy all-comers in later trials on candidate vaccines. Approved vaccines should be investigated in vulnerable populations and research should target label extension/modification or “impactful practice change”.
“APT investigations in the interpandemic interval need to utilise a wide spectrum of clinical research activities to keep up quality at the trial sites, in terms of enrolment capacity, standards of documentation, workup of biosamples, and any related logistics.”
Key points from the workshop
The paper highlights a consensus that APT methodology can be applied to vaccine trials, supported by the existing blueprint of a large-scale vaccine APT prepared for a Marburg virus outbreak. Although APT designs are “more complex” they have the potential to “accelerate knowledge generation”. Workshop attendees agreed that, while designs may be complex, execution “must be simple and straightforward”. The authors note that workshop attendees assigned importance to the value of “soft factors” in maintaining a clinical research network, including trust and leadership.
Professor Oliver A. Cornely of the University of Cologne is coordinator of VACCELERATE and reflected that “COVID-19 made us realise how important it is to be able to react quickly to an emergency” and “adapt vaccine studies” as the situation changes.
“This can significantly speed up the time it takes to generate the data required for political decision-making. However, this requires a paradigm shift in the field of clinical vaccine research.”
Pandemic preparedness remains at the centre of many sessions on the agenda at the Congress in Barcelona this October, so do get your tickets to join these important discussions as we explore different elements of the challenge. Don’t forget to subscribe to our weekly newsletters here.
