Another Problematic Trial: What You Can Learn - Keynote - 564
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- čas přidán 30. 01. 2024
- Vinay Prasad, MD MPH; Physician & Professor
Hematologist/ Oncologist
Professor of Epidemiology, Biostatistics and Medicine
Author of 450+ Peer Reviewed papers, 2 Books, 2 Podcasts, 100+ op-eds.
If you want to contact me, do it here: www.vinayakkprasad.com/contact
Google Scholar: scholar.google.com/citations?...
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Personal Website: www.vinayakkprasad.com
Laboratory Website: www.vkprasadlab.com
Podcast Website: www.plenarysessionpodcast.com
Academic Publications: www.vinayakkprasad.com/papers
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Man, this guy is good! He has the skill set to call out these greed heads who must be aware of the fallacy of their study manipulation. Keep up the great work Vinay. I have learned so much from the way you evaluate the quality(or lack thereof) of clinical trial design.
Keep Science Honest! Thank you, Dr. Prasad!
Dr. Prasad, people like you give me hope for our future
As control patients did not get standard of care, can those patients sue the investigators, institutions, IRB, and safety committee involved. If they can, and they can win, then maybe these types of unethical studies would decline.
I am an ignoramus. I know nothing but the trades. But I can see that diseases with high mortality are very corrupting. And patients are cattle to the system.
This is why more and more people will think twice to donate to cancer-related charities who may fund similar studies.
As someone who works in clinical research, these videos are extremely informative! I do wonder what is the thought process of PI’s who accept trials with substandard control arms.
Money or fame. I used to work for one such corrupt PI.
@@DylanYoung ughhh I hate to hear that. When I worked on site they would have research meetings to get input from different departments and with other oncologists.
"So what am I to think"
Dr. Prasad, I appreciate your impassioned voice and the critical appraisal of clinical trials that you bring to the table. You have done and are doing a great job on showing us the pitfalls, how not to conduct trials and how to see the results with a clear lens. However, I have to mention that you should do some talks on examples of actual well conducted phase III landmark studies that you would praise for having been well done. It will be good to elucidate some of the ideals that we should strive for and give real-world examples showing us that they are not pie-in-the sky naive ideals but actual achievable goals for which we can strive. I can only recall 1 study which you praised, the phase II dostarlimab study in dMMR CRC, which I don't think counts, seeing as it's an anomaly of a study.
Agreed. I think the TRANSFORM trial on Lisocabtagene in DLBCL was a good trial. It did everything right that the ZUMA-7 trial on Axi in the same setting did wrong. It would be very interesting to see a head to head comparison of these two trials and to hear what that means for the treatments - is Liso really better than Axi, or was Axi just unlucky to have a shitty trial?
I am just a simple elementary school teacher and don't understand Vinay in much of his terminology but is he saying that if I was in the control arm, I could very well die earlier because they purposely may have given me a placebo that does NOTHING just to make their new product look better? If that is the case, shouldn't these people be in front of a court of law?
Yes, that's what he's saying. Not sure if it's a criminal level or just malpractice (a civil suit). The uncle of a good friend of mine stroked out and died because they took him off his blood pressure meds and put him on placebo, I believe the family was able to get a civil judgment. Might be tough to get an involuntary manslaughter or negligent homicide conviction against someone with the cultural prestige of a physician-researcher, though. But I'd love to see it! Not only the researchers, but anyone else knowledgeable about what the usual standard of care should be but who officially signed off on conducting that study anyway.
You understand completely
Yes - and no.
The problem (as I understand it) is that they didn't control for post-relapse treatment in the placebo arm.
So the set-up is this:
You have kidney cancer, it is operated on, and no cancer can be detected (let's say 3-8 weeks post-op. At this time you are randomised to either X) the drug or Y) placebo. THIS IS WHAT ADJUVANT TREATMENT MEANS. (Shouting because people misunderstand what "adjuvant" means in this context.)
Then we follow over time. How many in each group a) has the cancer recurr, and b) how long do they live.
This study shows that people in the X - adjuvant group lived longer/less cancer recurred.
BUT
a) Some people in the X group would not have had recurring disease/died regardless. They are not correcting for that.
b) When cancer recurrs you treat it, optimally in this case - at this time, but not _everywhere_ on the planet_ - with the same drug given to group X.
It is (probably) not that they actively withheld the drug in question from those in group Y whose cancer came back. It is that in group Y there was also people who live somewhere where they don't give that drug as first-line treatment (or at all) when a relapse happens (too expensive, other treatments favored, whatever the reason).
There might also have been people in the placebo group Y that for some reason can't tolerate the drug they were investigating - hope not, that would border on research fraud (but there probably isn't easy clear contra-indications, but group Y got placebo, so any treatment-stopping side-effects wouldn't have occurred for them, for group X they would have been out of the study immediately.)
The problem here, even if every single patient was treated optimally _for their circumstances_ (is drug in question available or not), is that you are not comparing "give drug as adjuvant" with "best _possible_ care if relapse", you are comparing "give very expensive drug to everyone" with "a grab-bag of treatments from all over the globe".
Which means that your benefit of "expensive drug to everyone" will look much greater.
Giving the placebo in first line was fine because there was no alternative treatment. But afterr relapse, half of the people in the control arm received bad treatment, and that was unethical.
If you or one of your loved ones has cancer, it is really absolutely mandatory to be an informed patient. Read and understand clinical guideline recommendations and engage with your doctor. Ask questions. If they're a good doctor, they will try to answer them honestly.
Thanks again for caring about your patients!
Thank you for your reviews and being so passionate!!
listening was at least a good use of my ounce of brain. thanks
The only reason I'd like to do oncology is because of Dr Prasad. Thanks for inspiring people.
Great video as always Vinay. Keep it up!!!
Video idea- how do people find the standard of care for the particular cancer being studied? For example, I have a friend with metastatic breast cancer. She said that there are 3 drugs that are options for her- one that was not working, one that would give her horrible quality of life, and the other one that she is currently on. How do we find what is standard of care if we can't look at the literature?
Thank you. Keep pointing these out.
Thank you for your excellent work!!
Appreciate you showing light to granularity of trials that gets left out. Big pharma. All community oncologists see this data and make it new standard of care bc of OS benefit without getting this info. Adjuvant PDL1 therapy is not without toxicity as most docs treat it as a walk in the park
Are you still remain the best source of considering how to read a study and coming to conclusions based on evidence. I must say, I think that graduate students should just be required to follow you so that they learn how to read a study and understand research methods.
I think the issue is not exactly the methods, but it's that they are using the incorrect treatment on the control arm. If one was to read the study without knowing the standard of care in the field, they would not know that these studies are so bad. Unfortunately that means any scientist can't just read it and know it's bad. Though some of the things Dr. Prasad points out, like data presentation and missing information may be noticeable (but not guaranteed)
Agree with you..
Follow the money trail.
Yeah! Once one of my masters told me that the final purpose of the ICH GCP is not basically providing reliable data aout efficacy and toxicity of an IP, but to suppress cheating regarding trials... As this video points out, there are quite a room for improvement....
thank you, dr. Prasad.
I would really like something about your stance on the state of trials in radiotherapy. Maybe about the different modalities (conventional therapy vs. IMRT and SBRT, proton therapy, heavy ion therapy [Mayo Clinic in Florida is building the first facility in the US; the Japanese and Europeans are using it for some time yet], ....).
Very interesting.
I really enjoy your videos. Do you do the entire production or do you get help with editing and the content?
Sounds lke a big part of the ethics problem belongs to study approval boards. How does that get fixed?
The IRBs should be a check and balance, but they are failing. Better would be to not have the manufacturer involved in stidy design. We need truly independent researchers
But good point that these boards should also be accountable. One idea would be required information on the standard of care as a separate part of the IRB submission. Maybe worth some independent doctors. Though we know if the manufacturer pays them they will be corrupt
Your next Topic- The medicine Finasteride - (side effects, success, risks)
Treatment for enlarged prostate. One of the major side effects are prostate cancer. Are the benefits worth the risk? Other options for enlarged prostate? Many men have these issues, without good choices. 0:32
Why not use the General Population as your control arm? I mean of course those of the population that would be relevant as in adjusted for same / similar diagnosis, regardless of what (if any) other treatment they elected to receive. Common (and legitimate) practice in other intervention vs. non-intervention studies.
Excellent review as always. Ammunition for upsetting the oncology machine. Thank you
So tell us what works!!
Would like to hear the good doctor's thoughts on all cause mortality rates being so high. What are your thoughts as to the cause? Any studies to review?
Where you in the audience for the talk? Or at any of the talks you've critiqued in order to raise objections in real time?
Maybe they are celebrating making lots more money for very little benefit. Seems to be par for the course today because after all that leads to more treatment. This system sucks lol I am doing my best to avoid it now.
What's worse is that there may very well be no benefit at all, and an increase in harms.
This is shocking...there is a tremendous loss of confidence in medicine and pharma
I know absolutely nothing about oncology, but this reminds me of those miracle cure spam infomercials
Doc, my sister has had a scare. She’s had cancer before. She is getting scans in 2 weeks. In the meantime she is so scared and fearful. No doubt blowing things out of proportion. How to help people like her? She has no mental health professional. I also know she is abusing anti-anxiety medication and looking now for over the counter medication to calm her down. Sorry to throw you a question that is not pertinent to your video. Thanks
Also new law tha doesn’t require true informed consent for trials now - wow
I hear threes new bad news on CAR-T - you warned about that too
Great job professor. I’m curious though, you call out others, does anyone call you out?
Lmao I love how you tear this people down
Thanks for discussing sh***y oncology trials again and educating all of us, including clinicians.
tx
What would you recommend for the treatment of glioblastoma? I'm curious because my dad and close friend recently died of it and I live in a country where fully 30% of ontology research comes from a single corporation (the Canadian Cancer Society).
*oncology
I know two people recently diagnosed. One sadly passed away, the other a father barely 50. It’s a horrible cancer. Both males .
🙏✨💕
👋👋👋💯
Future NIH director 🤞🏽
During 30 years of watching oncology patients I’ve seen the vast majority on chemotherapy be so nauseated THEY CAN’T EAT, which I believe can be called “FASTING.” I understand fasting helps lower glycemia so that malignant cells dependent on glycolysis are starved of energy, that INSULIN which acts as a GROWTH FACTOR falls, and these help trigger AUTOPHAGY.
So when I see chemotherapy agents confering only MARGINAL advantage over each other I wonder if it is simply that they more efficiently induce nausea, fasting and autophagy? Those with T2DM or pre-DM are more prone to cancers (thanks to the years of hyperinsulinemia) and those who go into “remission” are always leaner than when diagnosed.
Some difficult cancers, like GBM and pancreatic cancers have shown some response to autophagy-inducing keto/carnivore diets and fasting. Perhaps that is the main agent for ALL the others when they remit too.
You can use same logic to explain all "diets" too. People have never heard of calorie restriction and its effects on health. Keto,vegan,carnivore,vegetarian,pizza+beer,all "work" in aleviating your symptoms or curing your disease AS LONG AS YOU'RE LOOSING WEIGHT.
Things change if you aren't.
And "ketones" are a God particle of nutrition.
You need a horn you can honk and a mascot to award these kind of bad studies.
As someone decently aware of what you're talking about - i agree with you that they should have done a protocol amendment to ensure that patients who progress get the current standard of care. However where you lose me 1. The whole front end/back end argument - what is your alternative proposal for this study? Especially in terms of recruiting patients both in the US and abroad? 2. The whole "its all orchestrated by the manufacturer" - its the same conspiratorial argument. Again, if you dont want the manufacturer to pay for all of this, whats your argument for the alternatives? Govt? Taxes? Public funds? You're always quick to point out flaws (and some are valid), but you rarely present an alternative case for some of these larger questions (which you ask) - makes you seem just like another "wannabe contrarian".
I'm just wondering what he's gonna do when he finds out radiometric dating is a scam. 😂
What?
Citation needed
@@nugsin4 look into how it works. It's basically a circular argument and doesn't match up to other dating methods we know match up to known history.
@@lokidarkbeard2647 Take a cross-section of a tree, C14 date the rings. Repeat this until you are satisfied that C14 dating is accurate. There are other methods, but the tree example is sufficient to dispel your confirmation bias toward young earth creationism.
@@Coolinteresting876 If you radiometric date anything we know the actual date of (like a historical pot for instance) you'll get a random date that is way off like 10,000 years off. When you radiometric date anything you give them a range of acceptable dates and they break your sample into parts and test each part and each part gives a different date. They then eliminate any dates outside the range you gave. They then take the top and bottom dates that are left and give you that as a range.