Mitchell Warren is AVAC’s Executive Director. This piece first appeared on Alan Whiteside’s blog.
Science, not politics, must lead to COVID vaccine approvals and delivery
COVID-19 has devastated communities and health systems around the world – but has created an historic global effort, leading to the unprecedented development of more than 165 potential vaccines against COVID-19. Equally impressive innovations are speeding vaccine testing within a rigorous scientific framework. Manufacturing and transportation capacity are being scaled up to distribute millions of doses of future COVID vaccines to those who need them most.
But developing COVID-19 vaccines at “pandemic speed” depends both on an unprecedented global research effort, and on innovative strategies to shorten the vaccine testing and distribution timeline. Each strategy should be weighed against relative risks and benefits, along with its potential to speed vaccine research. Speed is important, but not at the expense of ethics, safety, robust engagement, equitable access, and scientific rigor, including independent peer and regulatory review.
It seems every day brings an update – another vaccine enters into large-scale phase 3 trials; confusion about regulatory processes; concern about growing vaccine nationalism; and ever-present worry that politics will push researchers, developers, policy makers and regulators to move not just fast, but recklessly. Here is my list of key questions to try and make sense of it all:
1. Is one vaccine enough?
Simultaneous testing of large numbers of candidates across multiple vaccine platforms increases the chances of quickly finding a safe and efficacious vaccine. The current pipeline of COVID vaccines includes well over 150 candidates, with over 40 already in human clinical trials. Because of the extraordinary global interest in developing safe, effective and easy-to-manufacture COVID-19 vaccines as quickly as possible, the candidates represent a broad array of approaches – DNA, RNA, live-attenuated, inactivated, subunit and viral vector vaccines – some have been used for common current vaccines, while others are novel approaches. My organization, AVAC, created a COVID-19 Vaccine Pipeline Cheat Sheet. It offers advocates an at-a-glance view of the products, funders, research phase and considerations for some of the front-runner candidates, as well as refresher on the different platforms. (Editor’s note: this cheat sheet is highly recommended, it gives the basic information in an easy format).
2. How is vaccine development going so fast?
The traditional approach to vaccine testing runs preclinical and then Phase I, II and III studies in sequence, sometimes with gaps between each study. To speed timelines, some COVID-19 vaccine studies are advancing to the next phase of research as soon as data show the vaccine is promising and safe, even while the previous study phase is still underway. This accelerated approach has long been championed by AIDS and TB vaccine advocates – but those processes remain much slower with far fewer financial resources and much less pharmaceutical company involvement.
The COVID-19 vaccine response has ushered in a new era of collaboration in research and research funding. Based on models developed in HIV research, collaboratives such as the WHO-led ACT Accelerator, the US government’s ACTIV consortium and Operation Warp Speed and others are pursuing different approaches to speed COVID-19 vaccine development, by collaborating on COVID-19 vaccine science and funding. This includes advance purchase commitments, where public-sector and philanthropic funders negotiate a price and plan to purchase and distribute vaccines, before the vaccine testing process is completed. There are both risks and benefits to this expedited research – check out our guide here.
3. But is it safe?
Going fast cannot mean a license to go recklessly – the safety of those people receiving a vaccine at any point must be the primary priority, for any and every vaccine, and especially given the high political profile of COVID-19. Every trial has an independent Data Safety and Monitoring Board (DSMB) that reviews the data on an ongoing basis. Given the current politicization, the nine leading pharmaceutical companies recently signed a pledge to follow the science in development of COVID-19 vaccines, and promise to prioritize safety. But don’t just believe the companies – at least two of the most promising vaccine candidates in large-scale trials have paused their trials to investigate serious adverse events seen by the DSMB – these pauses are not uncommon and actually give us confidence that safety is, indeed, being put first.
4. Can I trust the process?
Regulatory review by agencies such as the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) is traditionally a methodical, rigorous process that can take many months. HIV advocates played a vital role in speeding review of new treatment and prevention options for HIV and AIDS. This created the compassionate use and emergency access systems being used today to help ensure rapid access to potential prevention and treatments for COVID-19. But regulatory review can only be accelerated to a point; it must be based on adequate data and allow for the thoughtful, informed and unbiased decision-making that is central to the product approval process. The FDA is currently under the most scrutiny given US politics, and here is our Regulatory Approval Primer for Vaccine Advocates. And my colleague Uché Blackstock of Advancing Health Equity and I recently wrote this commentary about Science, not politics, must lead to COVID vaccine approvals.
5. If we build it, will they come?
In our commentary, Dr. Blackstock and I argued why undue political pressure to speed the introduction of COVID vaccines is bad news, and threatens scientifically proven systems to protect public safety and research integrity – for COVID vaccines and for the vaccine enterprise generally. The consequences of any vaccine approval that appears to have been influenced by politics would be particularly grave for Black and Latinx communities in the US and marginalized populations around the world, who have real reasons to distrust both politicians and drug testing processes, and who are also at significantly increased risk for COVID infection and illness.
The rapid development of safe and effective COVID vaccines could help end this pandemic and strengthen worldwide faith in vaccines. But that can’t happen unless we take the signals of diminishing public faith in the process seriously and eliminate any sign of political interference in vaccine testing or approval. To protect health around the world, and advance health equity, we must insist on a COVID vaccine effort that is fast, transparent, thorough and safe, and guided by science, not politics.
6. Will the first one be the best one
The world will undoubtedly need more than one COVID-19 vaccine, especially to ensure enough manufacturing capacity. Plus, the first product to have a regulatory approval may not be the best – or the easiest to manufacture, the cheapest, or the easiest to deliver. But the first approval may challenge how to design and conduct future trials, as a placebo-control may not be ethical once we have an initial approval. Again, HIV researchers and advocates have grappled with these challenges for decades, so this is not new, nor a bad thing, but adds a degree of complexity to our future.
7. Who should get the vaccine? And who decides?
As complex as vaccine research and development is, vaccine delivery is even more so. In many respects, any regulatory approval is not the beginning of the end, but, rather, the end of the beginning. This is especially true for a vaccine that will be needed by billions of people. There many logistics questions: Are there enough glass vials and needles? Can companies make such large volumes in a matter of months? But who will buy these vaccines? And, most importantly, who will ensure that there is equitable distribution?
Already, many wealthy countries have made advanced market commitments to buy billions of doses. This buying power has led to concerns of “vaccine nationalism” and crowded out any potential for equity and public health strategy. As we know too well, COVID anywhere can quickly become COVID everywhere. WHO, GAVI and CEPI have joined efforts to create the COVAX Facility to, hopefully, mitigate against these risks and ensure global equitable access.
8. A vaccine is essential, but not sufficient
Even as we look towards a safe, effective, affordable and accessible COVID-19 vaccine sometime in 2021 (we hope), we already have critically important public health measures available today can help reduce the global burden – wear a mask; wash your hands; remain physically distant (while socially connected); and contact tracing. These measures will be just as important even when we have a safe and effective vaccine, while the world grapples with delivery challenges.
This is not unique to COVID-19; we have important lessons from 40 years of HIV – we need a comprehensive, integrated and sustained response, even if we had a vaccine (which, sadly, we still don’t) and especially when we don’t. We must act with urgency to develop vaccines because they are essential; and we must act comprehensively since a vaccine alone won’t be enough.