How Clinical Science Works: What You Need to Know if You Are Pregnant

If it is possible to see any kind of silver lining in the dark cloud of the COVID-19 pandemic, one possible one is that many people are getting a glimpse of how science works, how it is supposed to work, or how it sometimes falls short. Our ongoing discussions of the clinical trials of the handful of vaccines against SARS-CoV2 (the virus that causes COVID-19) and issues relevant to pregnancy, constitute one such example. From those discussions, let’s review the basic process for testing a candidate vaccine, which is as follows and is roughly the same for other new treatments, such as medications:

In the preclinical phase, the vaccine is tested at various doses in laboratory animals and typically some of the animals intentionally are given the disease that the treatment is designed to confront. If a candidate vaccine proves effective in generating an immune response and proves safe in the preclinical studies, the vaccine then can be tested in human volunteers, beginning with what researchers call a phase 1 clinical trial. In a phase 1 trial, a small number (such as a few dozen) healthy human subjects (volunteers) are given the treatment in order to confirm that the treatment is indeed safe. Based on a window of dosages and dosing schedules that has been calculated based on the pre-clinical studies and experience with other treatments, some of the volunteers are given a range of dosages, with a range of dosing schedules, while other volunteers are given a placebo, meaning not the actual treatment. In teasing out the data, researchers establish the limits on adverse effects in relation to dosing and dosing schedule, and determine whether it is safe to proceed to the next level of testing, phase 2.

In phase 2, a larger number of volunteers (such as several dozen to a few hundred) are tested, with the treatment or a placebo and researchers study how effective the treatment is. In the case of vaccines, one important way to look for an effect is to test the reaction of the volunteers’ immune systems, such as by measuring levels of antibodies produced against the infective agent against which the vaccine is supposed to protect. If the disease is a widely spreading pandemic, as in the case of COVID-19, the effectiveness of the vaccine can also be measured by using statistical methods to compare the rate that volunteers receiving the vaccine become infected in the community compared with the rate that volunteers receiving the placebo become infected. This second way of measuring vaccine effectiveness gets to be much more important in a phase 3 trial, during which the number of volunteers is expanded considerably.

With respect to the handful of COVID-19 vaccines that either are approved for emergency use in the population (Pfizer/BionTech, Moderna) or are close to being approved for such use (AstraZeneca, Johnson & Johnson), generally you first heard about them when the companies released information from the phase 3 trials. In each case, there was a press release in which the company or companies announced that company data from phase 3 trials were extremely promising, that the vaccine showed such and such percentage effectiveness. Information from the press release was read by journalists and used as the basis for articles and television broadcasts created for public consumption. Known as “science by press release”, this quick release of information has become the normal way of operating during the pandemic, but it actually represents a dissemination to the public of information earlier than the public has been accustomed to receiving it. In a very real sense, such information is premature, because the scientific process requires something called peer-review in which data from a study are presented in a scientific manuscript that is reviewed and critiqued by researchers who did not work on the study before. Only after such critique is the manuscript published and read, not only by other scientists, but also by science journalists, who then explain the significance of the study to the public, and to other journalists.

Meanwhile, in order for a medication or vaccine to be approved for administration outside of a clinical trial, government health authorities must review data that are published in peer-review articles. If the companies want to accelerate the approval process, also those data to which the companies were referring in any press releases that they have issued ahead of the scientific peer-review process have to be evaluated before a treatment, such as a vaccine, moves from a phase 3 trial into clinical use.

Whenever you hear about a new discovery or treatment, you should remember that it could have entered the news cycle at any point in the long, rigorous scientific process. Particularly when information on some development entered the news cycle prior to being peer-reviewed, you should view the information with a grain of salt. Often, when it comes to health topics, the temptation to make something into news for public consumption is great and people are talking about the thing with a greater level of confidence than perhaps they ought to be at the time.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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