Pharmaceutical regulators around the world tend to speed through drug applications in December and before major national holidays, according to new research that might raise questions about COVID-19 vaccines and other treatments under review.
A study by Lauren H. Cohen, the L.E. Simmons Professor of Business Administration at Harvard Business School, finds that 19 percent of all drugs approved worldwide are reviewed in December, twice the percentage of a typical month. However, drugs passed before an informal “desk-clearing” deadline, such as right before a major holiday, are more likely to cause serious adverse effects, including more hospitalizations, life-threatening incidents, and deaths.
The findings come at a time when regulatory agencies around the world are considering end-of-the-year emergency applications for COVID-19 vaccines developed with unparalleled speed. Could the risks uncovered by Cohen’s team apply to the coronavirus vaccines? The short answer: Yes, and the more rushed the approval process, the more likely patients will experience side effects from these drugs, Cohen says.
We asked Cohen to discuss how consumers—particularly vulnerable populations with other medical conditions—should assess the potential risks of COVID-19 vaccines and other drugs approved in December, and how regulators can build more trust with the public.
He teamed with University of Texas at Dallas Professor Umit Gurun and Danielle Li, a professor at the Massachusetts Institute of Technology, on the working paper Internal Deadlines, Drug Approvals, and Safety Programs, released by the National Bureau of Economic Research in November.
Danielle Kost: How should people interpret your research as they watch the COVID-19 vaccine process unfold?
Lauren Cohen: I would say two things. Number one, understand that this vaccine that's being approved is not like other approved drugs from the US Food and Drug Administration. Usually [drugmakers] have months and months to run trials, yielding much more data and evidence. This is important as the companies need this time to conduct all aspects of the drug trial and approval process, including allowing time for potential issues to materialize.
When you see an FDA emergency approval for a COVID-19 vaccine, don't interpret this as a normal “FDA approval.” I understand that the FDA is under pressure to say, “Our approval is our approval. There won't be any issues with this,” to keep confidence among consumers. But consumers need to go in with eyes wide open and understand that this approval is not equal to an approval of a drug that had 36 months or more and detailed phases of trials. This is a different kind of approval.
"Understand that this vaccine that's being approved is not like other approved drugs."
Expect side effects. That’s going to happen with this wave of drug approvals. They simply have higher risk. Now, are the benefits worth that risk? They might be. You’re going to have to make that choice as an individual. But consumers can make that choice more thoughtfully understanding the risk and benefit.
Number two, keep in mind that other drugs approved around this time likely got less mindshare from the FDA—the cancer drugs and drugs for other types of ailments. Those also are different kinds of approvals.
Even drugs that might be approved a month or two months from now, they should have been getting the amount of incremental time a drug applicant usually gets in its, for instance, seventh months in the FDA regulatory cycle. They're now not getting it because of the concerted push of resources toward these vaccines.
Kost: How can regulators maintain confidence in the drug review process, especially during such a politically polarized time?
Cohen: That is probably the hardest question. I don't know the right answer. They’re between a rock and a hard place. I would love for them to say what I’m saying; “Look, everyone should understand that this is risky.” And yet, as I mentioned above, I don’t think this is going to happen.
This AstraZeneca hiccup isn’t going to be the last one. I can all but assure you of that. Once we start implementing these [vaccines], we're going to find many other hiccups, and we all have to gird ourselves and be ready. If you think this is going to be like flu shots, it’s not. It’s simply not.
Relatedly, I would love if there were more straightforward communication, pointedly saying, “We intentionally did this. We understand that emergency use approvals have shortened review processes. We did this in the interest of public health and because we think that's the best thing for the world. However, make no mistake, this is a different ‘product’ than the typical FDA approval and has different expected attributes, including side effects.”
I understand from their regulatory standpoint that might be expected to be sufficiently confusing or nerve-inducing that they then don't do this.
And yet, I think [the FDA] should set up a system around these types of communications, so that following the pandemic they can say:
"I hope that we learn from both our missteps and what we're doing right ... I hope that the entire world can efficiently 'crowdsource' from each other."
“The next time this happens, we want you to know that emergency approvals might have to happen. And if they have to happen, what you saw happening during the COVID-19 pandemic was that we approved drugs quickly and there were significantly more side effects with those emergency approvals. We want you to know, going forward, we should all expect the side effects to go up by N times—two times, three times, four times, whatever it is. But we should all understand that the upside is still greater than that downside, justifying our potential need for emergency approvals.”
Maybe even those emergency approvals could then be gradated by risk scale. So, for these types of people [of a certain age or with particular medical conditions], this particular FDA emergency approval is even more risky. But for a different class of individuals, an FDA emergency looks just like a normal FDA approval from an expected risk perspective. That's where the difference is really important. The higher-risk population should understand that they are going to have four times the side effects, whereas the lower-risk population, fewer side effects.
Kost: How do you think COVID-19 might change how drugs are reviewed, post-pandemic, especially in emergencies?
Cohen: Look, I hope that we don't have pandemics often, but when we do, I hope we learn something about how to do this and the optimal logistics behind it.
Pre-purchasing things along the supply chain, like vials, and preparing dosages pre-approval—those seem like some reasonable things we can do in these situations.
We are tripping over certain parts of that now. Transportation components such as dry ice; we might be running into shortages because vaccines have to be kept at a certain temperature and kept for quite a while. So, if we run out of dry ice, it turns out that we could have done everything else right along the chain, and yet if we don’t have the dry ice, we can’t deliver and administer. These vaccines are then no longer functionally effective.
I hope that we learn from both our missteps and what we're doing right, and also the same from the experiences of other countries. I hope that the entire world can efficiently “crowdsource” from each other where we can: “Germany did this aspect especially well, while Canada did this well, China did this well, etc.”
If we all learn from each other’s innovations, failed and successful, the world will be in a better position to confront an event we all hope we never have to.
About the Author
Danielle Kost is the editor-in-chief of Harvard Business School Working Knowledge.
[Image: aleksejplatonov]
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