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’smake 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. About70% 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 atefficacy 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.
Hi-Risk/Recurrent/Advanced PCa Video Chat, Mar 4, 2024
AnCan is grateful to the following sponsors for making this recording possible: Bayer, Foundation Medicine, Janssen, Myriad Genetics, Myovant, Telix & Blue Earth Diagnostics.
View AnCan’s patient-centered selection of papers and presentations from ASCO GU 2024, one of the top conferences on prostate cancer treatment: • ASCO GU 2024 conference highlights https://www.youtube.com/watch?v=YweU8hjA0Lw&t=2s
AnCan respectfully notes that it does not accept sponsored promotion. Any drugs, protocols or devices recommended in our discussions are based solely on anecdotal peer experience or clinical evidence.
AnCan cannot and does not provide medical advice. We encourage you to discuss anything you hear in our sessions with your own medical team.
AnCan reminds all Participants that Adverse Events experienced from prescribed drugs or protocols should be reported to the pharmaceutical manufacturer or the FDA Adverse Event Reporting System (FAERS). To do so call 1-800-332-1066 or download interactive FDA Form 3500 https://www.fda.gov/media/76299/download
AnCan’s Prostate Cancer Forum is back (https://ancan.org/forums). If you’d like to comment on anything you see in our Recordings or read in our Reminders, just sign up and go right ahead. You can also click on the Forum icon at the top right of the webpage.
All AnCan’s groups are free and drop-in … join us in person sometime! You can find out more about our 12 monthly prostate cancer meetings at https://ancan.org/prostate-cancer/ Sign up to receive a weekly Reminder/Newsletter for this Group or others at https://ancan.org/contact-us/
Editor’s Pick: Here’s how to investigate if there’s a personalized/precision treatment for you (rd)
Topics Discussed
Exhaustive personalized/precision treatment pursuit; two successive Gents show us opposite sides of how a GU med onc beats a community practitioner; monotherapy enzalutamide; two more Gents manage their prostate cancer but not their heart issues; Dr. E is frank with an advanced patient but doesn’t reveal her cards just yet; our Gent thinks Guardant shows ‘weird’ results… or maybe they’re not so weird?; Pluvicto trumps olaparib in research and in practice; should spot RT metastatic directed therapy yield to systemic hormone treatment?; understanding the FDG scan
Chat Log
Jimmy Greenfield
sent: 6:22 PM
Mitoxantrone plus prednisone was previously accepted as standard chemotherapy for this stage of disease; however, docetaxel-based regimens have been shown to both palliate symptoms and prolong survival in hormone refractory prostate cancer.t.net
sent: 7:20 PM
Thank you, Rick, Dr. Bob, Len, and all, for a helpful discussion
Hi-Risk/Recurrent/Advanced PCa Video Chat, Feb 19, 2024
AnCan is grateful to the following sponsors for making this recording possible: Bayer, Foundation Medicine, Janssen, Myriad Genetics, Myovant, Telix & Blue Earth Diagnostics.
AnCan respectfully notes that it does not accept sponsored promotion. Any drugs, protocols or devices recommended in our discussions are based solely on anecdotal peer experience or clinical evidence.
AnCan cannot and does not provide medical advice. We encourage you to discuss anything you hear in our sessions with your own medical team.
AnCan reminds all Participants that Adverse Events experienced from prescribed drugs or protocols should be reported to the pharmaceutical manufacturer or the FDA Adverse Event Reporting System (FAERS). To do so call 1-800-332-1066 or download interactive FDA Form 3500 https://www.fda.gov/media/76299/download
AnCan’s Prostate Cancer Forum is back (https://ancan.org/forums). If you’d like to comment on anything you see in our Recordings or read in our Reminders, just sign up and go right ahead. You can also click on the Forum icon at the top right of the webpage.
All AnCan’s groups are free and drop-in … join us in person sometime! You can find out more about our 12 monthly prostate cancer meetings at https://ancan.org/prostate-cancer/ Sign up to receive a weekly Reminder/Newsletter for this Group or others at https://ancan.org/contact-us/
darolutamide achieves undetectable status after many years; should he radiate L4 – ask his QB!; PSMA scans at low PSA levels; intermittent hormone therapy requires active surveillance… and anxiety for some; Ac225 Tx in Austria followed by Ac225+Lu177 and a PARP with no HRR mutation; another Gent remains undetectable; no evidence of PCa from scans but inferior blood counts; Newbie at the back end – 20 year survivor finally requires 2nd line anti-androgen
Even though I have been on Treatment Holiday for 21 months I still get my PSA and testosterone blood test every month. I feel like I am then proactive. jim Marshall
Jerry Grimes, Brighton, MI
sent: 6:55 PM
Hey all, gotta run. All the best!
Peter Kafka – Maui
sent: 7:08 PM
With all this movement in the nuclear medicine field, are there specialized Nuclear Oncologists now working at Centers of Excellence or is much of this being managed by GU Med Oncs or Radiation Oncs?
Len Sierra
sent: 7:09 PM
Peter, in many instances, nuclear medicine specialists are used.
Len Sierra
sent: 7:19 PM
The European Medicines Agency (EMA) is the European Union’s (EU) equivalent to the FDA. The EMA is a decentralized agency located in Amsterdam, Netherlands, that evaluates, supervises, and monitors the safety of medicines for humans and animals in the EU and the European Economic Area (EEA). The FDA and the EMA work together to streamline efforts, share best practices, and promote human and animal health.
Len Sierra
sent: 7:40 PM
From Johns Hopkins: Blood cells are made in the bone marrow. The bone marrow is the soft, spongy material in the center of the bones. It produces about 95% of the body’s blood cells. Most of the adult body’s bone marrow is in the pelvic bones, breast bone, and the bones of the spine.
Hi-Risk/Recurrent/Advanced PCa Video Chat, Feb 13, 2024
AnCan is grateful to the following sponsors for making this recording possible: Bayer, Foundation Medicine, Janssen, Myriad Genetics, Myovant, Telix & Blue Earth Diagnostics.
AnCan respectfully notes that it does not accept sponsored promotion. Any drugs, protocols or devices recommended in our discussions are based solely on anecdotal peer experience or clinical evidence.
AnCan cannot and does not provide medical advice. We encourage you to discuss anything you hear in our sessions with your own medical team.
AnCan reminds all Participants that Adverse Events experienced from prescribed drugs or protocols should be reported to the pharmaceutical manufacturer or the FDA Adverse Event Reporting System (FAERS). To do so call 1-800-332-1066 or download interactive FDA Form 3500 https://www.fda.gov/media/76299/download
AnCan’s Prostate Cancer Forum is back (https://ancan.org/forums). If you’d like to comment on anything you see in our Recordings or read in our Reminders, just sign up and go right ahead. You can also click on the Forum icon at the top right of the webpage.
All AnCan’s groups are free and drop-in … join us in person sometime! You can find out more about our 12 monthly prostate cancer meetings at https://ancan.org/prostate-cancer/ Sign up to receive a weekly Reminder/Newsletter for this Group or others at https://ancan.org/contact-us/
Editor’s Pick: A penile prosthesis, and a lot of new hips. (bn)
Topics Discussed
Back on ADT, and now clobbered by fatigue — we suspect enzalutamide; exercise when walking’s too tough; he’s considering Pluvicto — but where’s the concordance scan?; FDG PET at low PSA?; when scanned, get the image CDs; new medonc OK’s ADT drug holiday at two years; more good reports on Dr. Bilusic; when dropping abi, taper prednisone cautiously; penile prosthesis surgery a success; insurance for yearly DEXA scans; urologists who don’t counsel on sexual dysfunction; making radiation a day at the beach; getting the word out on AnCan; hip issues and radiation; concerned about blood counts; shortness of breath and Flomax; drop abi, keep Lupron — or vice versa?; Peter K’s next move.
Chat Log
Alan Babcock · 7:21 PM
I have another meeting I have to attend. Hope to see everyone on Thursday.
Frank Fabish Columbus OH · 7:29 PM
has any read any information about the test trial of Anvirzel?
AnCan – rick · 7:35 PM
I know nothing about Anvirzel – but hopefully the Brains Trust can follow up
Frank Fabish Columbus OH · 7:37 PM
right. I think it is in Phase 1. not sure about PC trial. Hope to find out more info.
Len Sierra · 8:02 PM
For Frank Fabish: Anvirzel is a brand name for an aqueous extract of the plant Nerium oleander. Anvirzel contains two toxic cardiac glycosides, oleandrin and oleandrigenin. oleander is likely unsafe to take by mouth. It can cause a burning sensation in the mouth, nausea, vomiting, diarrhea, weakness, headache, stomach pain, serious heart problems, and many other side effects. Taking the oleander leaf, oleander leaf tea, or oleander seeds has led to deadly poisoning.
Frank Fabish Columbus OH · 8:03 PM
so I read about the extract
Frank Fabish Columbus OH · 8:14 PM
a friend of mine who had stage 4 metastatic PC with lesions on the brain. a brain bleed killed him Sunday. he was approved for this drug.
Hi-Risk/Recurrent/Advanced PCa Video Chat, Feb 5, 2024
AnCan is grateful to the following sponsors for making this recording possible: Bayer, Foundation Medicine, Janssen, Myriad Genetics, Myovant, Telix & Blue Earth Diagnostics.
AnCan respectfully notes that it does not accept sponsored promotion. Any drugs, protocols or devices recommended in our discussions are based solely on anecdotal peer experience or clinical evidence.
AnCan cannot and does not provide medical advice. We encourage you to discuss anything you hear in our sessions with your own medical team.
AnCan reminds all Participants that Adverse Events experienced from prescribed drugs or protocols should be reported to the pharmaceutical manufacturer or the FDA Adverse Event Reporting System (FAERS). To do so call 1-800-332-1066 or download interactive FDA Form 3500 https://www.fda.gov/media/76299/download
AnCan’s Prostate Cancer Forum is back (https://ancan.org/forums). If you’d like to comment on anything you see in our Recordings or read in our Reminders, just sign up and go right ahead. You can also click on the Forum icon at the top right of the webpage.
All AnCan’s groups are free and drop-in … join us in person sometime! You can find out more about our 12 monthly prostate cancer meetings at https://ancan.org/prostate-cancer/ Sign up to receive a weekly Reminder/Newsletter for this Group or others at https://ancan.org/contact-us/
Join our other free and drop in groups: Men (Only) Speaking Freely…1st & 3rd Thursdays @ 8.00 pm Eastern https://ancan.org/men-speaking-freely/ Veterans Healthcare Navigation… 4th Thursday @ 8.00 pm Eastern https://ancan.org/veterans/
Are eye issues related to hormone therapy?; Orgovyx AND Lupron vs Orgovyx OR Lupron?; Pluvicto may be in his future; time for PSMA scan and possible end to 6 yrs HT free; exercise guidance; awaiting PSA; next steps post chemo; monotherapy darolutamide; somatic testing; bulging disc gets in the way of exercise