Showing posts with label Brandolini. Show all posts
Showing posts with label Brandolini. Show all posts

Friday, April 19, 2024

Why “Reading” and “Doing Your Own Research” are not nearly enough….

 


 

Medical training is an exercise in repeatedly meeting people who know a lot more about the field than you do and hoping to learn something in the process.  It happens regularly – often several times a day.  It is a common occurrence to meet people with encyclopedic knowledge – not just of textbooks and papers but disease patterns and presentations as well as the best treatment approaches.  The knowledge can be obtained through straight didactics, informal seminars, bedside interactions, and direct observation.  It can be affiliative or adversarial. In other words, you might get the attending physician who asks you a series of questions until you run your knowledge base dry or you might get the attending who realizes that your life is difficult and details the pathophysiology while pointing you to the latest review to read.

All that dynamic learning happens in a certain time frame where everyone must focus on the problems of the day.  The recent COVID-19 epidemic is a striking case in point. During the years of my training and practice the pandemic of interest was the human immunodeficiency virus (HIV-1, HIV-2). I started to see those patients in residency training – typically for the neuropsychiatric manifestations. At the time there were full isolation precautions and we had to wear surgical gowns, caps, and masks to see the patients. There was also the concern about needlestick injuries and injuries sustained by during surgery on HIV positive patients – that was subsequently shown to be a rare occurrence.  

All primary care and specialty physicians need to have a knowledge of HIV/AIDS – because of the potential protean manifestations, the need to maintain medications, and for infection control purposes.  It is also useful to recall epidemiological and infectious disease concepts – the most relevant being that for a while the infectious agent of the disease was not known.  Early in the course it was characterized by epidemiological features. When the virus was eventually isolated – steady progress was made in the development of antivirals to the point where the virus can be suppressed and is no longer detectable.

Over the course of learning about the illness and its treatment – I observed a heavy toll on treatment providers. There were no effective treatments early on.  I had lunch every day with an infectious disease team who ran one of the early HIV/AIDS clinics. Providing care in that setting took an emotional toll on them.

Against that 40 year backdrop – Aaron Rodgers recent press conference stands in tragic contrast.  For a time, Rodgers assumed the role of inscrutable new age guru.  He refused to state his COVID vaccine status but talked in detail about the rejuvenative properties of ayahuasca.  But I want to focus on his 208-word commentary on HIV, COVID, and Dr. Fauci. The full video is linked above for viewing.  I will address his commentary on a subject-by-subject basis.

1:  There was a “game plan” in the 1980s to create a pandemic with a “virus that’s going wild.”

Multiple lines of evidence show that HIV resulted from cross species transmission of Simian Immunodeficiency Virus (SIV) existing in African primate species. The transmission occurred through infected blood or bodily fluid exposure from hunting (1).  The key concept is that many human pandemics originate from cross species transmission.  Further – there is ample evidence that the cross over to humans occurred decades before the first AIDS fatality occurred in the US in the 1980s.  The only "game plan" in place was evolution in nature - over millions of years.

2:  Dr. Fauci was given $350 million dollars to research this:

Dr. Fauci was appointed head of the National Institute of Allergy and Infectious Diseases (NIAID) in 1982. NIAID is one of 27 institutes and centers of the National Institute of Health (NIH).  The funding for AIDS research is available on several sites. In this paper Tables 4.2 and 4.3 give the research dollars as well as the distribution by institute. In 1982 for example – there was $3.6M in AIDS funding.  Looking at the 1990-1991 allocation NIAID got 53.1% of the research allocation. The detailed allocation of that grant money consists of intramural and extramural research funding as well as funding clinical centers of research with adequate patient numbers to advance the field. From that paper:

“The need for more—and more appropriate—facilities specifically for AIDS work was acutely apparent in early 1988 when NIH director James Wyngaarden and NIH AIDS coordinator Anthony Fauci testified before several congressional committees (U.S. Congress, 1988a:259, 1988c:331). Their concerns were echoed in the June 1988 report of the Presidential Commission on the HIV Epidemic. The commission noted that plans for AIDS office and lab space were seriously delayed, and recommended that intramural construction and instrumentation needs be assessed and made a high priority in future budget requests…”

When Dr. Fauci assumed control of NIAID, the total budget of that agency was $350M.  He described it as a relatively secondary institution, that he built up to a $6.3B agency over the next 38 years (3). 

3:  The only drug they came up with was AZT:

 Azidothymidine (AZT) was developed in 1964 by the National Cancer Institute (NCI) as a potential anti-cancer therapy.  It was ineffective but was included in screening as an HIV treatment where it stopped viral replication without damaging normal cells.  It was the first FDA approved drug to treat AIDS in 1987. Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) was founded at that time along with other networks though NIAID to conduct clinical trials in therapeutics for AIDS. Subsequent trials established more safe and effective doses as well as demonstrating a delayed onset of AIDS in HIV infected persons with AZT making it the first effective HIV treatment.

NIAID funded research for combination therapy, triple drug therapy and novel agents to the point where there are now 30 anti-retroviral drugs and new classes of therapeutic agents.  During Dr. Fauci’s tenure at NIAID, research has gone from antiretroviral (ART) based remission to clinical trials looking at ART-free remission of HIV.

 4:  An “environment” was created where only one drug worked

The environment was a research environment looking for treatments at a time where there were so many AIDS related deaths that it led to public outcry and activism. AZT was discovered as effective in a standard screening protocol, but additional clinical trials were necessary to establish doses, safety, and efficacy for FDA approval.

5:  Just like HIV – only remdesivir worked for COVID until there was a vaccine

Just like HIV – additional therapies became available for COVID (SARS-CoV-2) including nirmatrelvir-ritonavir (Paxlovid), simnotrelvir-ritonavir, and high titer convalescent plasma.  A recent review of the issue of vaccine versus pills for COVID concludes that it is a false dilemma and that they may have complementary roles (4). There is active research continuing in SARS-CoV-2 antivirals and no reason to expect that there will not be many additional medications.

6:  Dr. Fauci had a conflict of interest because of a “stake in the Moderna vaccine.”

Dr. Fauci has no stock in Pharma companies. The “stake” in vaccines are royalty payments that researchers are obligated to take, the majority occurring before the COVID pandemic. That standard and the average payments have been documented in the medical literature where Dr. Fauci is on record as having donated payments to charity (5).  Without having a detailed list of royalty payments, what they were for, and the outcomes it is difficult to make any additional comments except to say that there was no violation of NIH policy – in fact not accepting the payments was a violation. Royalties are based on discoveries and not getting products to market, FDA approval, or sales.  My further speculation is that the royalties are a small fraction of actual sales and company profits and the original NIH policy was probably designed to retain talented researchers who would otherwise be lost to private industry. Major universities and research institutes generally allow their faculty to accept consulting and royalty fees. I have worked in several settings where those arrangements were spelled out in the initial employment contract, including intellectual property ownership.

7:  Pfizer is also “criminally corrupt” based on a fine that was paid.

Large fines against pharmaceutical companies are the rule rather than the exception.  In looking at this list of the largest settlements most of the fines are based on regulatory laws having to do with off label promotion of drugs beyond what is indicated in the FDA package insert. Practically all of the penalties have to do with marketing rather than research or production. It has been well known for decades that Pharma companies aggressively market their products to physicians, hospitals, clinics, and now direct-to-consumer advertising to potential patients. You could look at a list like this and decide against using a company’s product – but it might mean not taking a potentially safe and effective drug.  The same type of enforcement actions are taken against companies in other fields such as information technology.

8:  People who can “do their own research” and “read” are commonly vilified for that if they question authority

There is a basic difference between authority and expertise. The only vilification that I have noticed is of experts. Dr. Fauci is an extreme example but during COVID it extended to many local public health officials. It was a direct product of the minimization of COVID by President Trump and many of his officials as well as the MAGA movement.  Further it has led to political violence that includes threats of physical harm to Dr. Fauci and many other public health officials.  These threats are unprecedented and have been attributed to right wing political rhetoric.

9:  Why should science be trusted if it can’t be questioned.

Science is continuously questioned and this is probably the most significant public misunderstanding.  Science is a process where results are continuously challenged and updated. The politization of the COVID pandemic illustrates what happens when people who are not trained in the scientific method get involved. Suddenly each scientific modification means that somebody was wrong or lying. Scientists are treated like politicians and the politicians feel free to say anything that is not grounded in science. 

That is not how science works. It takes actual observations over time to test hypotheses.  As one example – I have collected about 200 hypotheses on the pathophysiology of depression over the past 40 years and to date – there are not sufficient observations to prove or disprove them and get to the level of a theory of depression. An equivalent scenario is the endless speculation of the lab leak hypotheses versus the cross-species transmission hypothesis of COVID origins.  Although the probability lies in the direction of cross species transmission – there are insufficient direct observations to prove one versus the other and ample discussions of the lab leak hypothesis by people with a complete lack of expertise.

Finally, with the errors in Rodger’s statement – I would be remiss if I did not mention Brandolini’s Law. Simply stated:

“The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it.”

This is true – especially when the false argument does not have to be based on facts, process, or rigorous standards. The politization of COVID and many other health issues by the extreme right wing should be a lesson that is not forgotten.  This video clip is a case in point.

 

George Dawson, MD, DFAPA


Supplementary 1:  The NIH policy on royalty payments to inventors can be viewed at this link.  The abbreviation IC stands for the Institutes and Centers of the NIH.  More detailed information can be found at this link.  The NIH also has conflict of interest policy (see conflict of interest in Appendix 1).

 Supplementary 2:  A few relevant titles from my library - note dates. 


 


References:

1:  Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841. doi: 10.1101/cshperspect.a006841. PMID: 22229120; PMCID: PMC3234451.

2:  Institute of Medicine (US) Committee to Study the AIDS Research Program of the National Institutes of Health. The AIDS Research Program of the National Institutes of Health. Washington (DC): National Academies Press (US); 1991. 4, Supporting the NIH AIDS Research Program. Available from: https://www.ncbi.nlm.nih.gov/books/NBK234085/

3:  Anthony Fauci: a scientific adviser's role from HIV to COVID-19. Bull World Health Organ. 2023 Jan 1;101(1):8-9. doi: 10.2471/BLT.23.030123. PMID: 36593776; PMCID: PMC9795384.

4:  Papadakos SP, Mazonakis N, Papadakis M, Tsioutis C, Spernovasilis N. Pill versus vaccine for COVID-19: Is there a genuine dilemma? Ethics Med Public Health. 2022 Apr;21:100741. doi: 10.1016/j.jemep.2021.100741. Epub 2021 Nov 23. PMID: 34841029; PMCID: PMC8608621.

5:  Tanne JH. Royalty payments to staff researchers cause new NIH troubles. BMJ. 2005 Jan 22;330(7484):162. doi: 10.1136/bmj.330.7484.162-a. PMID: 15661767; PMCID: PMC545012.

6:  Mehellou Y, De Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J Med Chem. 2010 Jan 28;53(2):521-38. doi: 10.1021/jm900492g. PMID: 19785437.

7:  Burke RV, Distler AS, McCall TC, Hunter E, Dhapodkar S, Chiari-Keith L, Alford AA. A qualitative analysis of public health officials' experience in California during COVID-19: priorities and recommendations. Front Public Health. 2023 Sep 13;11:1175661. doi: 10.3389/fpubh.2023.1175661. PMID: 37771831; PMCID: PMC10525347.

8:  Ward JA, Stone EM, Mui P, Resnick B. Pandemic-Related Workplace Violence and Its Impact on Public Health Officials, March 2020‒January 2021. Am J Public Health. 2022 May;112(5):736-746. doi: 10.2105/AJPH.2021.306649. Epub 2022 Mar 17. PMID: 35298237; PMCID: PMC9010912.

 9:  Royster J, Meyer JA, Cunningham MC, Hall K, Patel K, McCall TC, Alford AA. Local public health under threat: Harassment faced by local health department leaders during the COVID-19 pandemic. Public Health Pract (Oxf). 2024 Jan 24;7:100468. doi: 10.1016/j.puhip.2024.100468. PMID: 38328527; PMCID: PMC10847788.

 

Sunday, December 11, 2016

Brandolini’s Law





There was an informative editorial in Nature this week by Phil Williamson - a scientific expert on ocean acidification.  I like the concept of bullshit and have referred to Professor Harry Frankfurt's classic essay on it many times.  I was not familiar with Brandolini's Law until I read the essay.  Simply stated:

Brandolini’s Law: “The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it.”

It is also more simply known as the The Bullshit Asymmetry Principle.

Williamson uses a political example from a libertarian web site.  The central piece of that article was that ocean pH was not decreasing and that climate change would lead to reduced carbon dioxide in the oceans.   Because the climate is not changing there is no worry that the ocean pH would change.  The original publication denied Williamson's rebuttal.  An opinion piece in a professional journal led the author of libertarian piece to write online that his work should be "squashed like a slug".  Nothing like elite scientific dialogue is there?

In the UK there is apparently a press watchdog called UK Independent Press Standards Organization (IPSO).  Williamson filed a complaint with them about the factual accuracy of the piece and is awaiting their verdict.  He goes on to illustrate how Brandolini's Law comes in to play in this situation.  The original author these days can essentially be anyone from a journalist to a blogger.  He points out that online journalism "seems to be subject to few if any rules."  That leaves anyone in the position of responding to a factually inaccurate claim at a distinct disadvantage.  There may not be any formal complaint procedure and there is probably no editorial hierarchy.  Many web sites count on bloggers and writers to produce content that they can attach advertising to and this content seem to have very little oversight in terms of accuracy.  Much of this content on social web sites makes up what has been referred to as fake news.

Williamson's position is very clear.  He thinks that these inaccuracies need to be responded to and corrected.  He accurately points out that the audience for the correction is not the authors, but readers who are interested in accuracy and science.  I don't think that the division is that clear for a number of reasons.  A large number of people really don't care.  They are involved in the emotion generated by the issue and don't make decisions based on facts.  That general attitude is promulgated by the political process in most countries.  This is rarely a rational discussion of the main issues of the day.  I think this goes a lot deeper than generating rebuttals.  There needs to be education on the difference between science and everything else.  A good example is Creationist based rhetoric and the denial of evolution.  Creationist advocates do not seem to recognize that they are engaged in a process that is nothing like science and therefore cannot scientifically prove anything.  They fail to recognize the basic issue that science is a process and not an immutable collection of writings written by ancient prophets and subject to many interpretations.  That failure of recognition also leads to a failure to recognize that they are  completely outside the field of science. They fail to recognize where they are and that the best critics of a scientific theory are the scientists in the field.

This failure of recognition is much wider than Creationists.  Journalists produce many examples, not the least of which is a consistent bias against psychiatry.  That bias is present whether or not there is editorial oversight.  A great example is the journalistic tendency to propose what psychiatry is and then proceed to attack that straw man.  And interestingly these outsiders with no training in medicine or psychiatry are often joined by insiders pushing the same arguments.  In one case a prominent journal editor came out and endorsed an anti-psychiatry book, proclaiming legitimate criticism when in fact the book was rhetorical.  I would not presume that medical editors are without common biases.  There are many forces producing misinformation.

I diverge a bit with Williamson's approach on refuting the misinformation and hoping for the best.  I think that there are additional considerations.  One thing is very clear - the head-in-the-sand approach taken by physician professional organizations in response to misinformation is clearly not a good idea and is sure to lose in the current propaganda war of misinformation and political corruption.  If there is a lesson with the current Presidential campaign it is that there is a very small margin between a typical fact less campaign and one where anything at all can be said whether it is true of not - and nobody seems to care about it.

That is foreboding for all levels of public policy, especially when the political spoils includes being able to appoint agency heads with not only a lack of basic footing in science but also a lack of knowledge about what constitutes science.  For the country to run and maintain some standards in science, technology, and engineering there needs to be a basic understanding of these fields in all branches of government and at the highest levels.  There is currently no better example of what happens when the unscientific manage the store than what has happened to American medicine.  We are not only cursed by work rules that are made up as we go and have little to do with the practice of medicine, but we we have to live with pseudo-scientific management practices that affect our work flow and and detract from the lifelong task of learning the science of medicine.  A few strategies I can offer as a blogger follow.  I also have additional strategies that I am going to keep to myself until just the right time.

1.  Don't feel compelled to engage - Twitter is an excellent example of how this principle is applied. Suddenly you are being given the third degree by some poster. That turns into misinterpretations of your statements and positions and before you know it personal attacks.  But it doesn't stop there. A new account pops up and mysteriously continues the attack.  Call them trolls or whatever you like but recognize the tactic. They don't really care what you have to say and are quite happy to waste your time.  Don't engage. Twitter gives you the option to block them and that works the best.

2.  Present the facts but counter the rhetoric - It is important to recognize the common forms of rhetoric without being pedantic.  The best way to do that is by pointing out the erroneous aspects of the argument and the overall form without naming the fallacy.  This sounds easy and it should be - but physicians and psychiatrists seem to be spellbound at times by the simplest arguments.  One common example is anytime a business executive shows up and talks about "cost effectiveness" - everybody shuts down.  Nobody seems to understand that this is just business rhetoric.  It should be as obvious as the fact that with 30 years of intensive management and "cost effectiveness" - per capita health care costs are 40% higher than the country with the next highest per capita expenditures and health care is certainly no better.  In the case of treating mental illnesses and substance use disorders it is much worse.  Somebody needs to stand up and say: "We are doing our part - when are you going to start to do yours." or "Get out of the way and let us do our work." or "Give us the resources to provide the adequate service or shut it down."   Rationing is clearly a very ineffective and costly way to provide health care services.

3.  Recognize bullshit no matter where it comes from -  Many of the arguments for health care reform are just plain erroneous.  And why wouldn't they be.  We now have a continuous supply of what are essentially blogposts on the front of our most respected medical journals.  How could anyone expect that 12 or 52 health care reform ideas each year for years would be worth anything?  All of the top posts that they have been implemented like the electronic health record, managed care as business intermediaries for government purchasers, pharmaceutical benefit managers, creating various financial incentives - have all been progressively worse ideas.  Sifting through the misinformation to correct what is false, what are lies, and what is bullshit is a tedious but necessary task.  As long as medical journals legitimize this constant stream of unscientific information - countering it will remain an onerous task.  The sources of bullshit go far beyond blogs and traditional journalism.

4.  Don't let anyone define you - A common strategy these days is that detractors tend to jump in and set the stage with false criticism.  It was easy to see this in political debates.  In medicine and psychiatry the same process happens and I have pointed out the dynamic on this blog.  I also posted a recent summary of how the release of the DSM-5 was a major source of misinformation, lies, and bullshit in 2015 but there are many more examples in psychiatry.

5.  Don't let the barbarians at the gate get you down - I tell aspiring physicians and aspiring psychiatrists the same thing - don't let the detractors or in these days trolls - get you down.  Psychiatry is a tough field because there will always be a lot of people blaming you for their problems.  This is where Brandolini's Law really applies.  There are numerous dialogues on web sites available where the game is to post as much misinformation, bullshit and lies about psychiatry in particular.  Entire web sites exist for that purpose.  Entering into that discussion and taking the opposite side of the argument can be more futile than the Law suggests.  It may take several orders of magnitude of effort and even then it may be futile.  The best approach is to just get the information out there in cyberspace in an independent forum where you know that it can be safely viewed.   That is one of the reasons that this  blog exists.

6.  The Internet is still the Wild West and that will probably never change in its current form - Williamson suggests that it may be possible to "harness the collective power of the Internet to improve its quality."  He suggests the global scientific community reviewing sites and rating them like film rating sites.  I am far less optimistic.  The first problem is the scope of that project.  The second would be consistency in ratings.  The third is that a rating in some sense is legitimizing.  It is a far better approach to ignore the ignorant.  The reality is that reputation protection web sites basically work by generating a lot of information designed to bury the obnoxious web site.  Most people find that if they contact a search engine about a web site that may be slandering them that they are met with a a relatively hostile response and a complete lack of interest in correcting anything.  That is true for even the largest search engines.  Google for example, clearly doesn't give a damn about your reputation.

7.  Brandolini's Law is a significant deterrent to keeping professionals engaged in educating the public - Physicians certainly find this out in a hurry if they decide to post a rebuttal in political or media forums that are populated by the ignorant, trolls, or those with a specific agenda.  That is more true of psychiatrists than any other specialty.  That has a dual effect of limiting feedback to those who might be interested and eliminating the most informed criticism.  It also has the added effect of adding professionals who may have legitimate criticism to antipsychiatry web sites where scientific criticism is clearly not the agenda.  It is a dangerous path of least resistance when legitimate professionals start posting on web sites dedicated to the destruction of the profession.

 These are just a few ideas about Brandolini's Law.  I did not write the most important one down and that is you can always just go off the grid.  Even then there are problems.  I talked with a psychiatrist about 10 years ago who was asked to give presentations at local churches on depression.  He eventually gave up because there were people in the audience who for various reasons were so disruptive that it prevented him from giving the interested people the information that they wanted.  Only psychiatrists could end up being heckled in church.  Bullshit can be presented in person just as easily as is can by typed online.

Williamson refers to a "rising tide of populism threatens the future of evidence-based government."  I don't think that we have ever had evidence based government in the US.  I see it as mostly a power dynamic here - influencing people by emotional ideas and shouting them down.

The only reason why that Brandolini's Law doesn't work in reality in the case of psychiatry is that at the end of the day, there are still people with severe mental illness - no matter who tries to deny it and a group of people called psychiatrists who are interested in helping them.  That is not necessarily enough to prevent the widespread demoralization of a profession.        


George Dawson, MD, DFAPA


Reference:

1:  Phil Williamson.  Take the time and effort to correct misinformation.  Nature 8 December 2016; 540: 171.


Supplementary 1:

My brother saw this post and commented that Brandolini's Law has "never been more true."

I reflected on that true statement and the continued widespread ignorance of science and came up with the following observation that might have been made by Casey Stengel:

"Good science cancels out bullshit and vice versa."

That probably captures why misinformation grows as exponentially as scientific information in any society.  It levels the playing field (to some degree) between the informed and the uniformed.