Monkeypox vaccine: a case study for real-world data

With health emergencies becoming more common, the world needs more efficient ways to test the safety and effectiveness of drugs, even if they haven’t yet completed the lengthy series of clinical trials the Food and Drug Administration usually requires. Data from the real-world use of new drugs offers an increasingly valuable and efficient way to do this.

That’s how authorities were able to determine that the initial vaccines for Covid-19 were safe and effective on a large scale in 2020. Because the virus was spreading so quickly, it took only a few months to begin to see the difference in outcomes between trial participants who received an actual vaccine versus those who received a placebo. Later, in 2021, when data showed that significant numbers of vaccinated people were becoming infected, health experts quickly instituted guidance for additional booster shots.

And now, in a welcome development that could have ramifications on future methods of drug approvals — and might even lead to more affordable drug prices — real-world data are positioned to play an essential role in evaluating the effectiveness of monkeypox vaccines.

Following last summer’s severe shortage of monkeypox vaccines, the FDA approved an emergency alternative dosing regimen for the Jynneos vaccine against monkeypox. This allows health officials to administer the shot intradermally, with each dose just one-fifth the size of the original approved dosage. The idea is to make sure as many people as possible get inoculated.

While such an approach, in which the vaccine is injected only into the outer layers of skin rather than into muscle or other deeper tissue, has not been tried with this or similar vaccines on a wide scale, there is research indicating that it could work — and has for other kinds of vaccines — as the skin contains many cells that defend the immune system.

With vaccine doses limited and no opportunity at any point in the past to test dosing changes, or even the clinical effectiveness of the vaccine against actual monkeypox exposure in humans, the only way to establish efficacy now, at least in the short term, will be to collect and analyze real-world data. In fact, the effectiveness of the original dose against actual monkeypox infection was tested only on animals while its safety, and the levels of antibodies produced in the bloodstream, are being tested on humans, meaning that scientists have little understanding of how well it works, how long it lasts, if it stops transmission, and other factors.

While the spread of monkeypox has slowed, the United States is still seeing about 200 new cases a day, and has been the location of one-third of all cases globally. It is against this backdrop that researchers at the Centers for Disease Control and Prevention and elsewhere are taking the opportunity to track data to see how well the Jynneos vaccine works at its lower dose amid actual exposure to the disease. The National Institutes of Health, in cooperation with the FDA, will also gather and study data on the intradermal injections to determine their effectiveness. In the face of real risk of infection as the virus continues to spread, being able to see whether or not those who get vaccinated also get infected will show how well the vaccine works (or doesn’t work) in its new dosing form.

Real-world data (and real-world evidence) can also play roles outside of public health emergencies like Covid and monkeypox. They can help determine the long-term effectiveness of many treatments, especially those subject to the expedited approval process, such as those used for rare diseases, and can help determine the value of drugs in general. In many cases, clinical trials are not enough to understand how well drugs really work. Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, has said that the clinical trial system is “broken” and that more use of real-world evidence could be an effective addition to the approval process.

The FDA has been taking steps toward using more real-world data outside of public health emergencies like Covid and monkeypox. In 2018, the agency issued guidance for use of such evidence in approving drugs. By 2021, when the FDA issued enhanced guidance on the topic, real-world evidence had been used in approving 90 medical devices and the new use of a drug, Prograf. But this is not happening enough in practice.

Failing to use real-world data means missing out not just on better understanding of the effectiveness of individual drugs but also on a chance to improve the entire pharmaceutical sector, including addressing issues like rising costs. The availability of more data on real-world outcomes from using drugs, especially gene therapies and other innovative and often very expensive treatments, would pave the way for pricing to take patient outcomes into account through approaches like value-based contracting, when health insurers base drug prices on how well drugs work in the people who take them, rather than just in premarket clinical trials.

Former FDA commissioner Scott Gottlieb has said that the ideal approach would be a hybrid system that uses both clinical trials and real-world evidence, with the real-world evidence serving as a way to further validate clinical trials, which are often limited to a small number of people and include only those participants likely to respond positively to the therapy.

Drugs will always need to go through supervised levels of lab tests and clinical trials. But real-world data can and should play a bigger role. Although changing the dose of the monkeypox vaccine due to a shortage is not ideal, if officials leverage this opportunity to collect and study data on its effectiveness amid an ongoing outbreak, they can show the important role that such data can play in evaluating drug effectiveness. Real-world data and evidence, when used in the right ways, can help better determine the effectiveness and value of a drug or vaccine, ensuring a more efficient approval process. This, in turn, could lead to a better and more fair health care system.

Girisha Fernando is the founder and CEO of Lyfegen, a Switzerland-based company focused on software analytics for value-based contracting in health care.