@VPrasadMDMPH's Threads
JUST OUT!
My colleagues & I offer a Modest Proposal to aid the most zealot proponents of cancer screening!
You know the wise folks who think overdiagnosis and false positives are overblown, and there is no harm greater than missing a localized ca.
Care for a TWEETORIAL?
My colleagues & I offer a Modest Proposal to aid the most zealot proponents of cancer screening!
You know the wise folks who think overdiagnosis and false positives are overblown, and there is no harm greater than missing a localized ca.
Care for a TWEETORIAL?
In recent years, the USPSTF has BACKED DOWN in cancer screening.
Annual -> biannual & 40--> 50 for mammography
PSA gets tossed around, yes, no, only after a discussion; not if over 70
But, backing down from screening makes some very mad.
(no, it has nothing to do with $$$!!!)
Annual -> biannual & 40--> 50 for mammography
PSA gets tossed around, yes, no, only after a discussion; not if over 70
But, backing down from screening makes some very mad.
(no, it has nothing to do with $$$!!!)
They argue that in balancing the benefits and harms of screening; there is no harm greater than the potential to MISS a curable cancer
They actually say things like this... (real quotes)
They actually say things like this... (real quotes)
These Duty Hour trials are a great to teach many many flaws in non-inferiority trial design.
From a scientific standpoint, they are quite poor.
They resemble the seeding trials used by the industry to bolster preconceived notions
A few points
From a scientific standpoint, they are quite poor.
They resemble the seeding trials used by the industry to bolster preconceived notions
A few points
1. Lousy endpoint
All trials must be judged by the primary endpoint. In this case it is a 1% NI margin at 30 days.
All trials must be judged by the primary endpoint. In this case it is a 1% NI margin at 30 days.
Medicare mortality at 30 days is roughly 12%
Accepting up to a 1% increase in mortality, so residents can work longer shifts is total madness.
Accepting up to a 1% increase in mortality, so residents can work longer shifts is total madness.
How Doctors Think [Thread]
You have an intervention X that people use for condition Y
X rose to prominence based on a little bit of bio-plausibility & some anecdotes
& that is about it
You have an intervention X that people use for condition Y
X rose to prominence based on a little bit of bio-plausibility & some anecdotes
& that is about it
After many years (and only if fortunate), a group of brave investigators test X in condition Y in a RCT
It is totally negative
Nothing improved at all
Some say, woah, lets rethink X
It is totally negative
Nothing improved at all
Some say, woah, lets rethink X
But many start saying, "yeah but"
Yeah but, they didn't do the RCT right
Yeah but, it still has a role with appropriate patient selection
Yeah but, it should still be used for pts with severe Y
Yeah but, the trial did not enroll the patients with most severe Y
Yeah but, they didn't do the RCT right
Yeah but, it still has a role with appropriate patient selection
Yeah but, it should still be used for pts with severe Y
Yeah but, the trial did not enroll the patients with most severe Y
Going to slowly tweet out 15 of the most interesting things I read, listened to and saw in 2018. With oncology/ health policy/ evidence themes
Starting with Same Dataset, Different Interpretations by @BrianNosek nature.com/news/crowdsour…
Starting with Same Dataset, Different Interpretations by @BrianNosek nature.com/news/crowdsour…
The point in this paper is if you give researchers the (a) exact same data set and ask the (b) exact same question you get a variety of answers.
Some point out that *some* of the point estimates are consistent....
Some point out that *some* of the point estimates are consistent....
Of course that is true, but other teams are reporting qualitatively different conclusions: some say no evidence of bias, others say bias
And, imagine a second what happens if...
And, imagine a second what happens if...
Cute & funny paper in the @bmj_latest
But unfortunately it furthers a narrative that is detrimental to medicine and scientific progress. Many may not see why.
Allow me to explain.. [THREAD]
But unfortunately it furthers a narrative that is detrimental to medicine and scientific progress. Many may not see why.
Allow me to explain.. [THREAD]
There are many people in medicine who think that the intervention they use must work. Some of these are invasive and costly interventions that have modest to weak bioplausibility, but no real trial evidence
The history of EBM shows that many of these interventions fail upon rigorous testing. So if you are a proponent of an unproven intervention, how can you avoid the call to test it rigorously?
This series by @charlesornstein and @katiethomas about financial conflicts in medicine is devastating; Should win the @PulitzerPrizes
Some thoughts
[THREAD]
nytimes.com/2018/12/08/hea…
Some thoughts
[THREAD]
nytimes.com/2018/12/08/hea…
In addition to outright failure to disclose, the profession treats disclosure as a token gesture
Aaron Boothby former @OHSUSOM student found 38% of conflict slides at ASCO flash faster than humans can read!
drive.google.com/file/d/1rBh7z7…
Aaron Boothby former @OHSUSOM student found 38% of conflict slides at ASCO flash faster than humans can read!
drive.google.com/file/d/1rBh7z7…
@StellaYooMD and @awadahmedMD find virtually identical findings in a different specialty
Why? Because docs don't give a #^$-- its a token disclosure
ascopubs.org/doi/abs/10.120…
Why? Because docs don't give a #^$-- its a token disclosure
ascopubs.org/doi/abs/10.120…
This is unbelievable
In JAMA, Ed Benz replies to @jsross119 paper with many incorrect statements
Shall we review?
jamanetwork.com/journals/jama/…
In JAMA, Ed Benz replies to @jsross119 paper with many incorrect statements
Shall we review?
jamanetwork.com/journals/jama/…
1. cancer has several established surrogate markers?
Uhhh, actually, most correlations btw surrogate & survival are lousy, especially in metastatic disease which has most approvals
drive.google.com/file/d/1FFkD2k…
Uhhh, actually, most correlations btw surrogate & survival are lousy, especially in metastatic disease which has most approvals
drive.google.com/file/d/1FFkD2k…
This is even worse for US FDA cancer drug approvals where most surrogates used are based on poor correlations or other low levels of evidence, aka not established
*true even for regular approval in violation of stated standards*
*true even for regular approval in violation of stated standards*
These two are the worst offenders for churning out garbage nutritional epi papers for years & building empires of BS, and no surprise they do not really understand the criticism, why the answer may not b RCT, but that so much of what this work is no better than nothing at all
They cherry pick the trans-fat story, and omit the thousands of other papers they put out that are utter garbage
Where is the full throated defense of nut consumption and prostate cancer
Yes, I appreciate the gesture by FDA, but in this brief thread I will explain why it is pretty much useless.
THREAD
THREAD
So... basically... We will use PFS or ORR in all these cancers for some traditional and some accelerated approval!
DEVASTATING Letter to the Editor in @BloodJournal for a paper published in @NEJM which (Wrongly) claims brentuximab AVD is superior to ABVD.
Care for a TWEETORIAL?
FYI I have a commentary under review that trashes this bad, bad trial but makes totally different points!
Care for a TWEETORIAL?
FYI I have a commentary under review that trashes this bad, bad trial but makes totally different points!
This is an AWFUL trial used to expand market share of a UBER costly drug Brentuximab and not actually answer the question of whether patients are better off..... In other words, par for the course in 2018
Lets take a look at key objections of the letter
First this....
POW!
Lets take a look at key objections of the letter
First this....
POW!
Then this...
BAM!
BAM!
My feed has blown up over the last day with
Persistent Reservations against Reforming the First 2 Years of Medical School Curriculum aka bad arguments
I find it funny because 6 years ago, I thought I had heard it all and wrote this
drive.google.com/file/d/1mLepDy…
[Well, Here's 2 cents]
Persistent Reservations against Reforming the First 2 Years of Medical School Curriculum aka bad arguments
I find it funny because 6 years ago, I thought I had heard it all and wrote this
drive.google.com/file/d/1mLepDy…
[Well, Here's 2 cents]
Let's be very clear about this topic: there are lots of stupid & inefficient parts to medical training, (especially scut work & bad work hours, rotating w disinterested attgs, bad teachers, etc.) I can't tackle it all !
I want to talk about the content of yr1-2 of med school
I want to talk about the content of yr1-2 of med school
Most schools spend 2 years learning a litany of basic science factoids so students can take a stupid test called USMLE step 1, and use that score to decide who goes into a coveted residency (plastic surgery and derm) and who goes into a less coveted one (family practice, peds)
Care for a TWEETORIAL on this paper?
(This will HURT)
This paper highlights the continued and abject FAILURE of cancer clinical trials & regulators to provide information for average cancer patients
Total failure
nejm.org/doi/full/10.10…
(This will HURT)
This paper highlights the continued and abject FAILURE of cancer clinical trials & regulators to provide information for average cancer patients
Total failure
nejm.org/doi/full/10.10…
First, consider the first FDA approved therapy for advanced or metastatic HCC-> Sorafenib
Approved based on these data
improvement in median survival from 7.9 to 10.7 months (typical for cancer drugs)
Approved based on these data
improvement in median survival from 7.9 to 10.7 months (typical for cancer drugs)
In the years after that approval, many providers noted that sorafenib was hard to prescribe. Our patients often self-discontinued the drug citing bad side effects.
If you used it, what is your experience?
If you used it, what is your experience?
This is a DEVASTATING look at the continued, perverse role of financial conflicts of interest that dominate FDA interactions by @cpiller in @sciencemagazine
This is a vitally important topic for drug safety
Some highlights:
science.sciencemag.org/content/361/63…
This is a vitally important topic for drug safety
Some highlights:
science.sciencemag.org/content/361/63…
These drug advisory committees (DAC) are very important
Not JUST because they decide on whether marginal drugs should be approved, but also because when the FDA makes up new, surrogate endpoints they use the DACs to "justify" them
Not JUST because they decide on whether marginal drugs should be approved, but also because when the FDA makes up new, surrogate endpoints they use the DACs to "justify" them
So @cpiller finds that after they vote, committee members often engage in direct financial relationships with the companies whose products they decide upon or competitors.... very cozy
Care for a TWEETORIAL #1 on colorectal cancer screening for avg risk people?
Today, we will review on this paper
@JAMA_current 2010
FYI Its a bit... controversial!
Today, we will review on this paper
@JAMA_current 2010
FYI Its a bit... controversial!
First, test your knowledge: which of the following screening interventions for colorectal cancer have RCTs showing reduction in cause specific (colon ca) death?
The answer is only FOBT and Sigmoidoscopy have direct RCT evidence of reduction in CRC death, though the extrapolation to FIT is widely considered plausible, given it leverages the same behaviors/principles of FOBT
Blood based screening has crap data FYI
jamanetwork.com/journals/jama/…
Blood based screening has crap data FYI
jamanetwork.com/journals/jama/…
I finally read this paper and feel prepared to comment
Because I don't think it is being interpreted properly by the Twitter community
Sorry folks, there is nuance here, and I hope to explain it to you.
[THREAD]
Because I don't think it is being interpreted properly by the Twitter community
Sorry folks, there is nuance here, and I hope to explain it to you.
[THREAD]
First, let's define health care waste
This is my definition. POLL COMING
This is my definition. POLL COMING
If we stent or give chemo or perform surgery, etc among patients with characteristics x, y, z, and that care does not improve outcomes, on average, in that group (or worsens it)----that is waste. Do you agree?
This is DEEPLY CONCERNING editorial behavior... and
I think its time we start talking about the Use, Misuse and Abuse of Academic Power. [THREAD] #cardiotwitter medscape.com/viewarticle/89…
I think its time we start talking about the Use, Misuse and Abuse of Academic Power. [THREAD] #cardiotwitter medscape.com/viewarticle/89…
First, the ISCHEMIA trial is clearly ruffling feathers since the primary endpoint was changed. It is a costly 100mi buck FEDERAL funded trial, and it just switched from a bias resistant to a bias prone endpoint
That's a big deal
That's a big deal
I read the article by Murthy and Eagle in FULL
I found it to be a lucid, stellar commentary about the deep and fundamental problems with the trial.
It was a SLEDGEHAMMER of clear thinking & reason
& it was persuasive
perhaps that was the problem
I found it to be a lucid, stellar commentary about the deep and fundamental problems with the trial.
It was a SLEDGEHAMMER of clear thinking & reason
& it was persuasive
perhaps that was the problem
TIme for TWEETORIAL PART 2 on mammographic screening.
A MULTI-part series on this topic
Today, we we will review this 2012 paper by
Archie Bleyer, a fellow OHSU faculty member, and.... H. Gilbert Welch
Sit down, It's a doozy.
A MULTI-part series on this topic
Today, we we will review this 2012 paper by
Archie Bleyer, a fellow OHSU faculty member, and.... H. Gilbert Welch
Sit down, It's a doozy.
Quick recap: In Part 1, we covered this provocative paper by Juni & Zwalen in the @AnnalsofIM on the randomized data for mammography.
Here we take a CLOSE LOOK at what mammography screening has brought us over the last 30 years in the USA
Here we take a CLOSE LOOK at what mammography screening has brought us over the last 30 years in the USA
Bleyer and Welch begin their paper with a clear, and indisputable insight
In order for mammograms to deliver benefit, they must
1. Find more early cancers (confined to breast)
2. Leading to fewer advanced cancers (in the lymph-nodes or distant organs) among women over time
In order for mammograms to deliver benefit, they must
1. Find more early cancers (confined to breast)
2. Leading to fewer advanced cancers (in the lymph-nodes or distant organs) among women over time
I want to do a TWEETORIAL on a controversial topic...
Mammographic screening
This is the first of a MULTIPART SERIES on Mammographic screening
This one will summarize one important paper in 2014
I start here because, this one is a dagger
annals.org/aim/article-ab…
Mammographic screening
This is the first of a MULTIPART SERIES on Mammographic screening
This one will summarize one important paper in 2014
I start here because, this one is a dagger
annals.org/aim/article-ab…
First, There are 2 things you need to know.
1 Most of the randomized trials we use to make inferences about the value of mammograms are old...
REAL OLD
From an era where breast cancer care bore no resemblance to today
1 Most of the randomized trials we use to make inferences about the value of mammograms are old...
REAL OLD
From an era where breast cancer care bore no resemblance to today
2. Back in those days, there was concern that researchers did a piss poor job of randomization, and/or poor job of endpoint adjudication (was the death due to breast cancer) often because the endpoint was not adjudicated in a blinded fashion
Care for a brief TWEETORIAL on the problem with TALKING POINTS?
and their blind acceptance
This one is for @AndraeVandross
and their blind acceptance
This one is for @AndraeVandross
Talking points are things we repeat or hear repeated that come to frame the way we think about a topic.
Problem is, after a few repetitions, the speaker believes the statement is true w/o question, and mind closes off to the idea it may not be
What do you think?
Problem is, after a few repetitions, the speaker believes the statement is true w/o question, and mind closes off to the idea it may not be
What do you think?
Here are a few talking points that my team and I didn't take for granted, and actually investigated & some broad lessons.
TP1: Has the reach of genome driven cancer medicine reached an "inflection point"?
Big names say it has...
TP1: Has the reach of genome driven cancer medicine reached an "inflection point"?
Big names say it has...
As promised, my TWEETORIAL on @JohnCarreyrou's BAD BLOOD!
(This ain't a book review; the book is excellent, pls read it)
This is about the broader problem Theranos reveals that underlies so much of Biotechnology and Medical start-ups
(This ain't a book review; the book is excellent, pls read it)
This is about the broader problem Theranos reveals that underlies so much of Biotechnology and Medical start-ups
I think the story of Theranos is particularly insightful because it shows how hype, lack of skeptical or clear thinking, money and hope can lead us to fail to adequately assess medical technologies until too late. Let me take you through the problem as I see it.
At the end of the day, Theranos claimed to have a product that would Save lives and transform medicine, and they hyped the hell out of it, and few were critical;
This was essentially how they claimed they would revolutionize the world
This was essentially how they claimed they would revolutionize the world
PINNED TWEET: This is going to be a place I store prior TWEETORIALS for easy reading
Wow, check out this AMAZING editorial in @NatRevClinOncol by the Editor-in-chief!!
nature.com/articles/s4157…
nature.com/articles/s4157…
First, I am grateful to hear our thought experiment that low barriers to approval can actually incentive broad, redundant low value trials agenda's was mentioned; Understanding that we are portraying what is possible
nature.com/articles/s4157…
nature.com/articles/s4157…
Yet, the truth is not far off, as regulators approve toxic drugs based on 1 trial, with nominal significance, even if the endpoint is a surrogate; and this might explain the 1000+ PD1 trials
nature.com/articles/s4157…
nature.com/articles/s4157…
As promised, a brief TWEETORIAL on why you should TWEET your criticism of a @NEJM paper rather than send a Letter to Editor (applies to others too), and ways NEJM could be better (aka more like @bmj_latest)
Why sending a LTE to the NEJM is a waste...
Why sending a LTE to the NEJM is a waste...
BACKGROUND: You read an NEJM article and you think it is stinks, you may know it stinks, or you may want some more data to about it to fully judge it; As you are thinking, many (superficial) readers are reaching the WRONG ideas encouraged by PRESS RELEASES & AUTHORS
You can TWEET out a rebuttal, or your can submit a LETTER (LTE) for consideration at the Journal. Let's compare them! Shall we?
This is really emblematic of how the FDA judges itself
Conduct an analysis and find neither tumor shrinkage (ORR) nor progression free survival (PFS) predicts how long patients live (OS), but then highlight fact that ORR predicts PFS and hope no one notices.
Sadly, we notice
Conduct an analysis and find neither tumor shrinkage (ORR) nor progression free survival (PFS) predicts how long patients live (OS), but then highlight fact that ORR predicts PFS and hope no one notices.
Sadly, we notice
This is literally the same game they play in their recent JAMA Onc paper
Sadly, I did notice
