What’s in a Clinical Trial? – Dr. John Antonucci’s Primer

by Rick Davis | Mar 21, 2024 | Active Surveillance PCa, Blood Cancers, Brain Tumors, Cancer Resources, Pancreatic Cancer, Prostate Cancer, Recent News

What’s in a Clinical Trial? – Dr. John Antonucci’s Primer

On Tuesday, February 27 a squadron of AnCan specialists attempted the impossible: to condense the essence of arguably the best scientific meeting on genitourinary cancer research in the world into 1 hour of intelligible, useful information. A couple of hundred scientific poster and oral research presentations from the American Society of Clinical Oncologists annual GU meeting (GU ASCO24), made available and understandable to us AnCan’rs? You can view their attempt as well as the slides  at https://ancan.org/patient-highlights-from-the-2024-asco-gu-conference/ and judge how they managed.

To prepare for the session, a basic understanding of research is very helpful. It starts when scientists comes up with a question. For example, “Does Lupron do any good?” They then design a study to answer the question.

Types of studies:
Not every study is an experiment. In an experiment, the scientist does something to the subjects, such as try a new drug, and compare them to a control group, which doesn’t get manipulated. In observational research, the scientist studies the subjects but doesn’t do anything to them.

     Randomized controlled trials (RCT) are a type of experiment that are highly thought of. If you want to find out if Lupron is any good, you can find 2 groups of subjects with prostate cancer, give one group Lupron, and the other group a placebo (ie no medicine, although you still administer the fake dose). You have to be careful that the 2 groups match, because if you accidentally put most of the healthy patients in group A, they will do better but mess up your conclusion. This is the controlled part: you have to make sure both groups match except for the experimental manipulation. This is partly done by randomizing, assigning the subjects at random to the groups. At the end, you find out how long each group lived (or some other pre-established endpoint) and make a conclusion. This type of study is an experiment. It is also prospective: you create data as you go along which makes it a good study.

One of the several types of observational studies is the cohort study. Cohort studies follow groups to see how they do. For example, you could follow 1000 men over time, and see if the smokers get more prostate cancer than the nonsmokers. This could give a clue into what contributes to prostate cancer and how to prevent it. These studies are often prospective (looking into the future) but can also be look-back, or retrospective as well. A well-known cohort study in prostate cancer is the Canary Cohort that looks at low/intermediate Active Surveillance; or the Framingham Heart Cohort.

A cross-sectional study can answer questions like, what percentage of 50-year-old men have had a PSA test? You have 500 fifty year old men answer the question, and get your conclusion. It’s at one point in time. (The opposite is a longitudinal study, following subjects over time.)

Qualitative studies don’t collect numerical data like the others. If you want to find out what life is like on Lupron, you interview lots of men on the drug and get the big picture. The opposite is quantitative, where numerical data is collected.

Naturally, it makes sense to have lots of subjects in any study so you don’t get fooled by chance. For instance, you could flip a coin twice, get heads twice, and wrongly conclude that all coin flips will be heads. So big studies are better than small ones. The number of subjects in a study is known as n. Small ‘n’s make results suspect.

The chosen study type depends on the question, the ethics, and the resources.  Only an experiment, like an RCT, can make a cause-and-effect conclusion, because it’s randomized and has a control group. Other studies can discover correlation; that’s when two phenomena occur together but causation is unclear.

There are studies of studies as well: A Meta-analysis will review and combine several similar studies to make the results even more convincing. A Literature review will review many studies, pick the best, and create a summary for us.

Basic science research uses instruments like petri dishes and microscopes to study molecules or cells or tissues; these are in-vitro studies. Lupron started in basic science research. Then it progressed to animal or in-vivo studies. Treatments that look promising at this stage progress to human clinical studies.

Clinical Trial Phases
You will hear human clinical studies presented as Phase I, Phase II, or Phase III studies. According to the FDA, Phase 1 has 20 to 100 healthy volunteers or people with the disease/condition. It lasts several months and is to test for safety and dosage. About 70% of drugs move to the Phase 2, where up to several hundred people with the disease/condition are studied for several months to 2 years looking at efficacy and side effects. Approximately 33% of drugs move to phase 3, where 300 to 3,000 volunteers who have the disease or condition are studies for 1 to 4 years to deeply look at efficacy and monitoring of adverse reactions.  

A drug like Lupron, when it did well at all these phases, was then submitted to the FDA for approval. After approval it was still followed, in phase IV or post-marketing research, as it was given to thousand of patients. Keep the phases in mind if you volunteer to be a research subject.

Clinical tests
One last thing. How do you measure if a test is any good? What if someone asks, “Is PSA any good as a test for prostate cancer?” There are two key measures to consider: sensitivity and specificity. Sensitivity asks, “If prostate cancer is present, how good is the test at detecting it?” This measures the test’s ability to identify those with the disease correctly. Specificity, on the other hand, asks, “If prostate cancer is absent, how good is the test at correctly identifying those without the disease?” This measures the test’s ability to identify those who don’t have the condition correctly. Both measures are crucial in evaluating the effectiveness of a diagnostic test.

Clinical tests can be either predictive–A predictive test is designed to predict the likelihood of a specific outcome or response to a particular treatment or intervention.  –or prognostic–a prognostic test is used to estimate the likely course or outcome of a disease, regardless of treatment.

Your AnCan team looked at all those ASCO meeting presentations with an eye toward good study design, importance, whether it’s an experiment or not and if so what phase it is, is it prospective, does it have a large-n, and is it of interest to men in our group. Hopefully reading this will make it easier to understand the ramblings of our AnCan Mods.

 John Antonucci MD   dr.john@ancan.org

(Editor’s Note: AnCan is planning a webinar on clinical trials in 2024.)