Biostatistics and epidemiology
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A study is conducted to determine the long term effects of a novel vaccine against the SARS-CoV-2 virus, which causes coronavirus disease 19 (COVID-19). To do so, researchers followed individuals who had received the vaccine for one year. They discovered the vaccine is associated with an increased incidence of fever of unknown origin and new-onset heart failure with reduced ejection fraction in 25 patients out of the 1 million total patients who were followed. Based on these results, an additional warning about these adverse events is added to the investigator brochure for the vaccine. Which of the following clinical phases does this study most likely belong to?
Content Reviewers:Yifan Xiao, MD, Antonella Melani, MD
Contributors:Talia Ingram, MSMI, CMI, Tina Collins, Sam Gillespie, BSc
Clinical trials are scientific research studies that help determine the safety and effectiveness of an intervention.
This could be a new medication, vaccine, device, procedure, or anything with therapeutic purposes.
Clinical trials are done on humans, and are often the last step before an intervention is approved for use by the general public.
Now, the main goal of a clinical trial is to find out if the intervention actually works, and for that, there needs to be an experimental group that gets the new intervention and a control group that doesn’t.
In addition, researchers should eliminate as many external factors as possible, as they could affect the results.
Now, there are multiple ways to design a clinical trial, so let’s go over a couple of them.
The gold standard is the randomized, controlled clinical trial.
So as an example, let’s say there’s a new vaccine that’s being developed for a viral epidemic.
As the participants, we’ll need a group of people who tested positive for the infection.
Each person will be randomly assigned to either the experimental group who will receive the vaccine, or the control group who will usually receive a placebo.
Now, if there’s already an effective treatment available for a disease, it would be unethical to give a placebo, so the control group will receive the available treatment instead.
Now, to limit bias, both the people administering the intervention and the people receiving it won’t know who’s in the control group and who’s in the experimental group, and this is called “double blind.”
When the people assessing the data also don’t know who’s in what group, it’s a “triple blind”.
Having placebos and blinded studies will help ensure that any difference between the results of both groups is most likely due to the intervention that’s being tested and not external factors.
Another type of design is the pre-post study, where an individual will be their own control.
So for example, to test a medication for rheumatoid arthritis, we could measure the pain and joint mobility of the test subjects before giving the medication, and then again after they’ve been treated for a specific amount of time, to see if there’s any improvement.
A third type of design is a factorial design, which allows for the study of multiple interventions and their combinations.
So for a new antidepressant medication, you can compare the effect of the medication combined with psychotherapy, the effect of a placebo medication with psychotherapy, antidepressant medication and placebo psychotherapy, and the effect of a placebo medication combined with placebo psychotherapy.
Okay, so when it comes to medications and vaccines, clinical trials usually go through 4 phases.
Phase I is focused on assessing the safety of the new medication in humans.
So let’s say a group of researchers are developing a new antiviral medication for a new pandemic.
For phase I, the research team will need to find a small group of test subjects, which is often made up of healthy volunteers or patients with the disease being treated by the medication.
This is because people with other illnesses like gastrointestinal, liver, or kidney problems might absorb, metabolize, and eliminate the medication abnormally and give incorrect data.
Next, the research subjects will be given the medication and then be closely monitored in a hospital setting.
In general, an initial dose based on animal studies will be administered, and the dose will be gradually increased until a safe but potentially therapeutic level is found for use in phase II.
Phase II is done in a clinical setting with medical supervision for safety.
During this process, the pharmacokinetics and pharmacodynamics of the medication are also studied, and information like time to maximal plasma concentration, elimination half life, and bioavailability are collected.
Potential side effects are also identified and studied intensively.
For some medications with severe side effects, like chemotherapy agents, it’s unethical to test them on healthy subjects.
In these cases, people with the disease that exhausted all other options can volunteer to participate.
Clinical trials are research studies that test how well new medical treatments work in people, and they are used to determine whether a new treatment is safe and effective. In most cases, people participating in clinical trials do not receive any direct benefit from it.
Clinical trials usually involve two types of participants: the experimental group, the control group, and the placebo group. The experimental group receives the new treatment; the control group receives a standard treatment or placebo (a medicine or other preparation with no therapeutic effect).