What’s in a Clinical Trial? – Dr. John Antonucci’s Primer
On Tuesday, February 27 at 16:45 EST sharp, a highly-trained, elite squadron of AnCan specialists (Speak for yourself Dr. John -rd) 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 is 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 results. 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. As you’ll see on Tuesday, small ‘n’smake results suspect.
Which type of study is chosen 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 was given to thousand of patients. Keep the phases in mind if you volunteer to be a research subject.
Screening Test Evaluations
One last thing, which came up in last week’s group: How do you measure if a test is any good? For instance an experimental test for the feared neuroendocrine cancer might be evaluated. Or what if someone asks, “Can PSA test for prostate cancer?” Two ways: you ask, “If prostate cancer is present, how good is the test at detecting it?” This is sensitivity. And, “If the test is positive, how often is prostate cancer really there?” This is specificity.
Your AnCan team looked at all those ASCO meeting presentations from last month. They looked 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 reding this will make it easier to understand the ramblings of our AnCan Mods.
Bang your drum… it could make you smarter and healthier!
I don’t want to work I want to bang on the drum all day I don’t want to play I just want to bang on the drum all day
–Todd Rundgren
Twice in the last several months, the topic of drumming came up in our AnCan Men Speaking Freely group and it generated some excitement both times. So this month’s invite will be on that topic.In my former practice whenever I have given a non-verbal treatment there is a big relief that no talking is involved. In bypassing the verbal and left-brain systems we gain access to a typically unused part of ourselves. I wonder if we can use this approach to cope with our serious illnesses and have a better life?
Our brains have a characteristic called plasticity, the ability to change. You may have heard of this regarding the little finger brain circuit of violinists; it grows as they become proficient. Drummers also have different brains than the rest of us. They have fewer, thicker nerve fibers between the two halves of the brain. They have more efficiently organized motor cortices. (Schlaffke, 2019). Because of this, drummers can do things that we can’t. They can coordinate the two sides of the brain better, and perform motor tasks with greater efficiency. They can play different rhythms with each hand and foot at the same time.
Schlaffke’s subjects had drummed many hours per week for decades. But Bruchhage’s (2020) subjects trained for only 8 weeks and showed several changes in the cerebellum plus changes in the cortex, showing not only cerebellar plasticity but also communication and coordination between the cerebellum and brain sensorimotor areas as well as areas for cognitive control.
Drumming is very complicated, which is why it’s unfair that the lead guitar and vocal guy gets all the girls (Greenfield, J. 2022).
For some reason, there is a close association between beat synchronization (integrating auditory perception with motor activity) and reading ability in children (Bonacina, 2021). Higher synchronization ability predicts better literacy skills. Maybe early intervention involving drumming can improve literacy in kids?
Cahart et.al (2022) showed that drumming can improve behavioral outcomes for autistic adolescents and elucidated some of the neurology involved. Does this mean it could help us?
Drums have been used for millennia for healing, inducing trance, and even psyching up soldiers.
We have learned that drumming is not just about waking up the right brain, but also about connecting the sides of the brain, and the cerebellum with the cortex. It can induce alpha brain waves. It can release endorphins. Even T-cells respond to drumming (Bittman). It induces present-moment experience, which we often work toward to deal with death anxiety. Interpersonal connections are made when people drum together. Despite the effort involved, it induces relaxation. I have come across papers describing drumming and music therapy for a wide variety of emotional problems and currently, there are 8000 music therapists in the US.
How about for us? We see above the possibility of reductions in anxiety, tension, pain, isolation, depression, and over-thinking the past and future. There are many studies of music therapy in ICUs, with patients on ventilators, easing hemodialysis pain, with positive results. Also, helpful with narcotic use, social integration, and depression. MSKCC uses music therapy.
With terminal cancer, there is data showing that music helps breathing, QOL, psychospiritual integration, reducing pain in chemotherapy, radiation, and helps pediatric breast and lung Ca patients (Ramirez 2018, Hilliard 2003, Burns 2015 Tuinmann 2017, Barrera 2002, Li 2011, Lin 2011). Atkinson (2020) found improvement with fatigue. I couldn’t find any studies focused only on Prostate Cancer.
Well, all this scholarly stuff is really unnecessary to anyone who ever banged a pot with a wooden spoon. Kids love it. Adults love situations where it’s OK to be wild and make noise, such as drumming circles and Pound classes. It’s just fun and feels good.
Dr. John Antonucci
Editor: Dr. John wrote this for our Men Speaking Freely Reminder on Dec 7, 2023. It’s such a perceptive, helpful and instructive piece, AnCan wanted to share it widely.
Last month’s Under 60 Stage 3 & 4 Prostate Cancer meeting was small, intimate and produced a true gem from Down Under to benefit all AnCan’rs …
For the life of me, I forget what raised the topic … maybe a Death with Dignity discussion – but Aussie AnCan’r, Steve Cavill told us about the ICE “In Case of Emergency” Checklist Document that he and his wife Leonie, who occasionally attends our Care Partners Group, have both completed. Steve and Leonie reside in the suburbs of Melbourne and are currently heading towards mid-Winter.
This ICE Checklist takes much, if not all, the difficulty out of placing your key information in one place. Like your vital passwords to your laptop, phone or bank accounts; names of key individuals in your life and more. You know .. all that information making it possible for someone to piece your life together if you’re suddenly no longer with us.
Frankly it’s information we should all compile no matter how old. With this checklist guide at hand to march us through it, there can be few excuses. Just remember, this version of the ICE checklist was created in Oz, so it may not be fully applicable Stateside. If one of our US volunteers has time to ‘Americanize’ it, I feel sure it will be greatly appreciated – we have very few solicitors in the US and a few too many attorneys!
Here’s the checklist document in Word format ICE Document Template Now do your part …. and a BIG THANK YOU, Steve Cavill!!
I am writing with a very heavy heart to report the death of our dear Board Member, Advisory Board Member, Moderator, Participant and my good buddy, Herb Geller PhD G-d Rest His Soul.
The loss of dear Herb z”l is already reverberating around AnCan and will undoubtedly amplify as more learn of his demise. Herb touched many well beyond his Advanced Prostate Cancer ‘Brains Trust’, Moderators, Peers and Participants. The Blood Cancer group got to know him well when he attended regularly on behalf of his brother. The Pancreatic Cancer folks met him when he showed up for his next door neighbor. Our Men Speaking Freely Group loved and respected him for sharing his fears and concerns. Members of our Advisory Board got to interact with Herb as did Medical Academics and others who participated in AnCan’s research projects.
Here are a few of the words I already see bandied around –
“kind, smart, caring, thoughtful”
“My heart is heavy and I’m at a loss for words. There is something I’m feeling that I can’t express sufficiently”
“this is the deepest hurt since we lost Dominic (2015)”
“Thanks to each of you for your loving support of him and all of us for each other.”
Herb passed away from advanced prostate cancer that had evidently morphed into small cell/neuroendocrine like (NEC) disease. A late diagnosis just one day before he entered the NIH, his place of work, identified this. Herb was scheduled to undergo tests for his highly elevated endocrine markers, however the source was now evident on admission. The NIH never appeared to acknowledge or treat him for this diagnosis. It finally added a neuroendocrine oncologist to Herb’s team after 21 days after repeated AnCan prodding from the date of admission. Herb underwent research procedures related to Cushing’s Disease and its symptoms. In due course, AnCan will follow up as appropriate.
Never one to give up the opportunity to sail anything from a small dinghy to an ocean-going yacht, Dr. Herb Geller was a nationally recognized expert in neuro-biology; a profile is available on the NIH site. Herbie loved a a good Scotch, in Skye or anywhere else. On his request, AnCan did its best to sneak in a wee dram just to wet his lip in the final days but the ‘powers that be’ prevented us. I’ll have one for you tonight, Herb! And, we’ll make sure both your AnCan posters get written up for submission with credit to you.
Herb is survived by his wife of 55 years, Nancy, Director of the Office of Biostatistics for the National Heart, Lung and Blood Institute at the NIH. Also his younger brother, Ken, an eminent Supreme Court Advocate kennethsgeller@gmail.com. We wish Herb’s family and many friends, especially his “AnCan Family”, much comfort. May Herb’s memory always be a blessing – it certainly will be here at AnCan.
For our Jewish readers, Herb’s z”l Hebrew name is Chanan Moshe ben Aaron v’Sara; he died on 25th Nisan.
WEBINAR – ‘The Invasion of the Prostate Snatchers: 13 years Later’: An Evening with Dr. Mark Scholz
By Howard Wolinsky, Peter Kafka and Ben Nathanson
Dr. Mark Scholz, author of Invasion of the Prostate Snatchers, drew a record audience to his AnCan webinar on January 30, 2023.
Registration worldwide was close to 1,000 — nearly double the previous record — with more than 600 watching live.
Scholz’s talk, “Invasion of the Prostate Snatchers: 13 years later” discussed how prostate cancer treatment — and overtreatment — has progressed since the book’s original publication in 2010. The book took aim at a urological-industrial complex performing surgeries on hundreds of thousands of low-risk patients, leaving many impotent and incontinent.
Half those men, he argued, could safely have been followed without aggressive treatment. Scholz, a medical oncologist, coauthored the book with patient Ralph Blum. A new edition was issued in 2021.
While urologists today still unnecessarily “snatch” prostates, Scholz said, the number is far fewer since active surveillance was endorsed in 2007 as a safe and effective strategy. And he said radiation therapy, which he had criticized in the past, also has become safer and more effective.
Still, men come to him thinking they have only two options: surgery or radiation. In fact, they have more than a dozen options, based on the severity of their disease and their preferred balance of treatment and side effects. He urges patients to “obtain facts and apply principles” — replacing assumptions about cancer with informed decisions.
Even for the smaller, but significant segment of men diagnosed with more serious grades of prostate cancer including metastatic, Scholz explained that there has been so much progress in new treatment modalities with limited side effects that many men are living long productive lives living with their disease and not dying from prostate cancer. Dr. Scholz stressed that unlike other cancers, prostate cancer is much slower growing and the rush for treatment in most instances is not necessary.
After the talk, Scholz answered 40 minutes of audience questions.
AnCan moderator Joe Gallo produced the webinar, and moderators Peter Kafka, Howard Wolinsky, and Ben Nathanson relayed questions. Alexandra Scholz, CEO of Prostate Cancer Research Institute, the nonprofit education initiative run by Scholz, edited the video, and she and Peter Scholz lent production assistance.
Invasion of the Prostate Snatchers: An Essential Guide to Managing ProstateCancer for Patients and Their Families by Mark Scholz, MD & Ralph H. Blum (Other Press, New York; August 2021)
Summary: “Invasion of the Prostate Snatchers” is a guidebook for prostate cancer patients and their partners. It is of great interest to patients with low-risk to favorable intermediate-risk cancers considering early disease Active Surveillance (AS) since it critically evaluates types of treatment. AS is close monitoring of lower-risk prostate cancers. A patient with prostate cancer (Blum) and a medical oncologist (Scholz) present information patients can use in making key decisions in their care throughout the prostate cancer disease path.
My experience: This book was a just-in-time godsend for me. It was released in August 2010. I was in a holding pattern awaiting a follow-up biopsy at that time.I wasn’t diagnosed until Dec. 4, 2010. My cousin, Maxim Schrogin in Berkeley, California, who was diagnosed in January of that year and was on AS, told me the next day that the first thing I needed to do was get this book. I had it in hand within minutes via Kindle. I devoured “Prostate Snatchers” as I prepared for a second opinion on what, if anything, to do about this cancer.
I went against my first urologist’s advice to go on AS and avoid the side effects of active treatment because AS was not the mainstream approach then. My first urologist tried to rush me into the OR though I only had a single core of less than a millimeter of very low-risk Gleason 6 cancer. That’s the lowest level of prostate cancer,
What I liked about the book: This book helped give me the courage to consider AS and go off the then unbeaten path. It helped prepare me to see Scott Eggener, MD, at the University of Chicago, he told me I didn’t need surgery and was “the poster boy for AS.” A new edition of the book, which came out in August 2021, covers these changes and more. The world has changed since 2010 as reflected in the new edition.” Now,,
multiparametric MRIs have been accepted as the first step when PSAs rise, followed by targeted biopsies. The interval between biopsies is generally longer. Genetic and genomic testing has become more common in the U.S. to help determine whether biopsies are needed and which cancers are likely to become aggressive.
Authors Ralph and Mark plus my wife Judi and cousin Maxim were my “support group” as I became an “active surveillor.” There were no support groups devoted to AS then. I would not meet another patient on AS for seven years. We now have support and educational groups devoted to AS, including those from AnCan and Active Surveillance Patients International.
AS patients are not so rare anymore. We now make up the majority of low-risk patients.
Tips from the book: The book is chock full of background on prostate cancer and actionable information. For example, Scholz weighs in on prostate-specific antigen blood testing: “A PSA is considered a ‘cancer test.’ One savvy patient’s advice is to think of PSA as a nonspecific indicator, like the ‘check engine’ light on your dashboard. An elevated PSA may be due to harmless inflammation, recent sexual activity or even a laboratory error. The first step toward investigating the cause of a high PSA is to repeat the test. If the PSA remains high, the next item to consider is that the prostate may be enlarged (BPH).” The authors point out that if PSA is rising, patients should consider multiparametric MRI and targeted biopsy. Back in 2010, those weren’t quite on the table for discussion.
Nitpicks: No book is perfect. The authors, I think, missed an important discussion on the pros and cons of transperineal vs. transrectal biopsies. Transrectal biopsies can lead to sepsis or other
infections and can miss certain areas in the prostate that may harbor cancers. Also, the authors stressed that patients should seek out MRIs with 3-Tesla magnets. To get into the weeds, some new models with 1.5-Tesla magnets can work just as well and are used routinely at the National Cancer Institute. Discuss these matters with your doctor.
In conclusion:“The Invasion of the Prostate Snatchers” provides a critical look at the prostate cancer “industry” and serves as a bible for newbies considering AS and a reminder to those of us who have been on AS for many years of just why we took the now mainstream approach to low-risk prostate cancer. You can live with these “lame” cancers and not die from them. But you need to maintain
surveillance to detect if your cancer is becoming more aggressive.
Reviewed by Howard Wolinsky, editor of TheActiveSurveillor.com and AnCan moderator
With terminal cancer, there is data showing that music helps breathing, QOL, psychospiritual integration, reducing pain in chemotherapy, radiation, and helps pediatric breast and lung Ca patients (Ramirez 2018, Hilliard 2003, Burns 2015 Tuinmann 2017, Barrera 2002, Li 2011, Lin 2011). Atkinson (2020) found improvement with fatigue. I couldn’t find any studies focused only on Prostate Cancer.
