Fuck That.

David Healy - Time to abandon evidence based medicine?

• You can't trust trial data
• You can't trust reviews (not even Cochrane Reviews)
• Real significant problems (e.g. increased suicides on Prozac) can be "statistically not significant"
• Data is hidden
• Evidence vs. Evident: Large controlled trials are needed to weed out the drugs that don't work – drugs that "really" work show their effects in small trials. If you need 10,000 people to show an effect, something is fishy.
• If alcohol were a novel substance, a (hypothetical) trial could be made that would show that alcohol works as an anti-depressant drug
• In this (hypothetical) "alcohol as anti-depressant drug" example, one could even get alcohol as drug to be included in the NICE-guidelines
• One (hypothetical) 6 week (!) trial alone (!) could "prove" that the economy would save lots of money by putting people on alcohol for depression
• And this (hypothetical) one 6 week trial would be enough "prove" that doctors would insist that patients should take this drug for life(!), because the condition is life-long
• If a drug causes symptoms (e.g. more suicides), which the disease can also produce, then a control trial can not answer that question for you
• Clinical trials are not the answer:
  1. If both the illness & the drug cause a problem
  2. If the clinical population is heterogenous (if the underlying condition is unknown)
  3. If the researchers don't know what they are doing
  4. Clinical trials cannot provide patient level answers
  5. Clinical trials do not reveal cause and effect
• Doctors will defend prescription drugs – and hereby delay investigation into adverse effects by 15 or more years

And all that is not even including the carnage done by quacks…

Fuck that.

We have all these amazing medical, technological and scientific advances, which should put us in a position to fight diseases in a way that would make all the Pasteurs and all the Enders' and all the Salks and all the Sabins of past times green with envy. Where is the evolution in medicine? Why does it seem to me that we are stuck in a dead end?

The medical profession does well with clearly defined illness – say HIV/AIDS – that, if left untreated, lead to clearly measurable, visible adverse outcomes. But things like depression? MS? T2DM? In all likelihood, the treatment may lead to worse outcomes than if the illness is left untreated.

And this hits me at the moment. My doctor is willing to try out medication for my ME/CFS and therefore I'm currently looking into what agonist drugs are available to stimulate the alfa 2A receptor which is shown to be involved in at least subgroup of patients. Besides

• the almost total lack of scientific interest in ME/CFS by the medical commuity that leads to a situation where every person with ME/CFS is going from one "personal drug trial" to the next because guiding trial data is non-existent,
• besides not having any certainty whatsoever what actually the pathology is in my case (besides some personal indication that the alfa 2A receptor might be involved for me as well),
• besides not knowing if a stimulation with an Ad2A agonist is actually the right thing to do, if it is the Ad2A in my case,
• and besides not knowing what the actual (vs. claimed) spectrum of adverse reactions of these drugs is,

besides that I am totally at loss whether the supposed alfa 2a agonists actually do what the pharmaceutical industry claims they do.

Should I give Guanfacine a try? Or rather Tizanidine? Maybe Xylazine? What about Lofexidine?  Is Brimonidine only for occular hypertension?

I know, let's play guinea pig! And if one doesn't work, or makes me awful, then we try the next! Oh boy, what fun.

I feel like I might go to a pharmacists, and at gun point take any random medication and try that – and not be worse off…

But it sure is nice to see a psychologist like David Healy sharing his good insight into the problems of his profession and giving his best to address them properly.

The Great Chronic Lyme Mirage

I found some interesting comments by Phillip J. Baker (who seems to be associated with the American Lyme Disease Foundation) underneath an otherwise not recommendable article & discussion (or rather an article & discussion which can only be recommendable as a negative example for the display of confirmation biases and cognitive dissonances).

Especially this comment by Phillip J. Baker struck a chord with me:

Believe what you will, Phyllis, but you are wrong. Ceftiofur and ceftriaxone are chemically different in structure. Embers et al. have provided no assurances in their work that they have similar PK and PD properties, let alone the same MIC. It is incumbent upon them to provide such data, as well as to show that therapeutic regimen used was adequate to clear the huge inoculum that was used to produce a disseminated infection. Obviously, their experimental design did not mimic the Klempner study, which is what Mario was initially funded to do. Why he chose to use ceftiofur is for him to explain, not me. As I said before, ceftiofur has not been approved by the FDA for use in humans and there are no published data showing that it is effective for treating borreliosis in animals, let alone humans. There is one report showing that it is not effective for treating borreliosis in ponies.

Phillip J. Baker
on February 24, 2012 at 1:52 pm

http://lymedisease.org/news/lymepolicywonk/lymepolicywonk-was-this-important-lyme-study-hidden-for-12-years.html#comment-3798

He goes on to notice in another comment:

I must say that I find it strange that the term ceftriaxone is used throughout the Embers et al. paper, and it is only in the first paragraph on page 9 that it is first mentioned that ceftiofur was actually used. I find that very strange indeed.

So to claim that Lyme is still active despite anti-biotics, Embers et al. have to pull these two tricks:

1. Use a "huge inoculum" to intruduce an amount of pathogens not encountered in the wild, causing an "massive disseminated infection" not encountered in the wild.
2. Use an antibiotic that (most likely) is not effective in clearing the pathogen (let alone in this massive disseminated infection) – and hide that as good as you can.

What Phillip J. Baker describes are the tactics of quacks.

No wonder anybody with at least a couple of working brain cells left*, who looks into the matter comes to the conclusion that "Chronic Lyme" is a BS quack diagnosis.

And just for the record: I do think that these patients have an organic disease, which severely affects their lives – however there is no evidence** that this disease is Lyme. There are many many diseases that can cripple your live, and possibly some of which are yet of unknown.

* As to so called "Lyme Literate Medical Doctors" ("LLMD"):
They do not seem to have any working brain cells left. My (purely anecdotal and not evidence based) advise is to stay away from medical doctors who have no working brain cells. LLMD? Just say no. Choose a doctor instead with working brain cells, this is usually better for your health.

** As to any non-standard tests used to detect "Chronic Lyme": I can offer you an even more reliable Lyme test! I will match any price, just give me a call!

Gallo a Quack?

Well, who knew that? It seems like Gallo was quite a quack. In 1990 he claimed to have a cure for Kaposi's Sarcoma, when all he had was some experiments with mice (Crewdson, page 354-355).

Any other scientist doing such a thing would qualify as quack, so should we make an excuse for him?

Kentucky Fried Cardiovascular Research

The Scientist: A Decade of Misconduct

A senior cardiovascular disease and diabetes researcher at the University of Kentucky has been found guilty of falsifying data over the past 10 years.

Federal investigators have censured a former University of Kentucky (UK) senior biomedical researcher for serial scientific misconduct over a 10-year period, including the falsification of data in grant applications, progress reports, and published papers. The US Office of Research Integrity (ORI) announced the findings last week (November 20) with a notice in the Federal Register.

A joint investigation carried out over the course of 2 years by the ORI and the UK found that Eric Smart, who studied the molecular mechanisms behind cardiovascular diseases and diabetes, had falsified or fabricated a total of 45 figures—mostly images of Western blots, a technique used to identify proteins—in seven grant applications, three progress reports, and 10 published papers, some of which were cited more than 100 times, according to Thomson Scientific’s Web of Knowledge. The notice says that Smart also reported experimental data from knockout mice that did not exist.

“This is surprising and disappointing news to me,” said Philippe Frank of Thomas Jefferson University in Philadelphia. “Dr. Smart's papers were highly cited in the specific caveolae/cardiovascular research field.” William Sessa of the Yale University School of Medicine told The Scientist by email that he was “shocked at the extent of misconduct,” and that the reporting of data for knockout mice that did not exist in grant applications “is very problematic indeed.” But, he added, “since I do not know what aspects of the figures were incorrect or misrepresented, it is difficult to assess the impact on the field.”
…

Retration Watch has this to report:

Specifically, ORI finds that Respondent:

Falsely reported in Figure 14 and associated text in NIH grant applications R01 HL07897601 and -01A1 that experiments were performed to determine if endothelial-specific caveolin-1 null mice were protected from saturated fatty acid-induced atherosclerosis, when these mutant mice did not exist in the laboratory at the time; Dr. Smart also falsely reported the use of these mice in related progress reports R01 HL078976-02, -03, and -04 and in three (3) additional NIH grant applications: Figure 11 in R01 HL088150-01, Figure 11 in U54 CA116853, and Figure 9 in DK063025-01A2

So nothing to see here.

Continue to avoid saturated fat, and take your statins – as the good doctor said.

And while some people may actually and genuinely be surprised (and may actually and genuinely believe that saturated fat is the nutritional anti-christ), I am not the the slightest bit surprised that one needs to fake studies to come to the faulty paradigm which is en vogue now for decades in cardiovascular research. I guess if you work with a faulty paradigm, there is no other way but to fake results to uphold that faulty paradigm.

Money and Fraud

Too little money for research, and you get fraud as a result. Though too much money seems to be a problem as well:

Texas's $3 billion [per 10 years] cancer research agency is in trouble again: Its peer review system appears to have come apart. The entire eight-member scientific review council of the Cancer Prevention Research Institute of Texas (CPRIT) is stepping down, with most citing concerns about the integrity of the agency's peer review process. Many members of CPRIT's 100-strong roster of peer reviewers have begun to follow.

Looks like the NCI isn't the only one that got a little bit sloppy with billions from the "war on cancer".

Oh my

Oh my, not something specific to medical sciences:

… I know of people that have given a purportedly crippled software to a collegue to sabotage his project. I’ve been violently attacked verbally for having dared talking with my supervisor of a project I was collaborating with, because she feared that I wanted to “steal” her credit. I’ve seen more than once people “helped” during a project, only to find all credit for their work taken by the nice and smiling people who scammed them by “helping” them. There are endless horror stories like that. Everywhere.
…

The ones I’ve seen thriving in Cambridge, apart from geniuses (there are a few), are the guys who cling to a simple ecological tenet: Find your niche, where you are indispensable, and keep it in your claws at all costs. This means basically that these people do always the same thing, over and over again, simply because it’s the lowest-risk option. I could have done the same (I was pretty skilled during my Ph.D. in a quite obscure but interesting biophysics experimental technique) but I thought that doing science properly was also about learning and broadening your expertise. How wrong I was.

You can imagine yourself what does it mean also for research in general: Nobody takes risks anymore. Nobody young jumps and tries totally new things, because it’s almost surely a noble way to suicide your career.
…

“Actually, it’s worse than you know…”

The life of frauds and whistleblowers in the medical sciences:

…
I travelled to Telford last month to hear Wilmshurst give a lecture to the Royal Statistical Society on libel and other barriers to exposing research misconduct. It took me back to 1996 when we invited him to come to the BMJ and give a talk—behind closed doors—to our staff and advisers and colleagues from the Lancet. He reeled off case after case of misconduct, many of them involving prominent people. The audience listed intently, but I was unsure of the reaction. Might somebody leap up and say “How dare you accuse x of misconduct. He is one of the great men of British medicine”? In fact in my memory the reaction was the opposite. People said things like “Actually, it’s worse than you know…”
…
Now 16 years later Wilmshurst has a longer and updated list, and somebody in the audience asked if he thought things are getting better or worse. He thinks probably worse: he’s had seven whistleblowers contact him in the last two months.
…

Lot's and lot's and lot's of anecdotes and case studies, but when will there be more research as to causes and mechanisms, and when will there be real consequences to prevent this in the future?

Perhaps strangely it was his first story that best captured the corruption that Wilmshurst has been fighting all his professional life. It was the early 80s at St Thomas’ Hospital in London, and Wilmshurst was doing research into amrinone, a new drug for heart failure manufactured by Sterling Winthrop, a company since taken over. The drug was supposed to increase myocardial contractility, but Wilmshurst found that it didn’t. Worse, it had serious side effects. Wilmshurst and his boss prepared to publish, but Sterling Winthrop, the manufacturers of the drug, threatened legal action. The company also asked if Wilmshurst and his boss would be willing to meet with their experts. They agreed. The message was that St Thomas’ was getting very different results from everybody else and that their lab would be discredited if they were to publish.

And by the way, the next person who ignores the countless lifes of patients that have been endangered by medical fraud and says "Well, but science is self correcting" will be diagnosed with a mental disorder, pumped full of fraudulently tested pharmaceuticals and put into a lunatic asylum for the rest of his life.

One of the things that seems to make Wilmshurst so cheerful is the black humour of his stories. Many of them involve doctors who are guilty of misdemeanours but who sit in judgement on others. He told the story of Peter Richards who decided to bury the fact that Clive Handler, a doctor, at Northwick Park Hospital, was found guilty of using NHS research funds to subsidise his private practice at a time when Richards was medical director of the hospital and chair of the professional conduct committee of the GMC. Previously he had been dean of St Mary’s Medical School, prorector for medical education at Imperial College, and chair of the Council of Deans of UK Medical School and Faculties. When Handler eventually appeared before the GMC, the GMC’s lawyers ask that Richards stand down from chairing the committee. As Wilmshurst said, it’s as if a judge at the Old Bailey were to say “I’ll have to excuse myself from hearing this case as I helped the accused bury the body.” After having to stand down from this committee Richards continued to chair other conduct committees. Wilmshurst told several stories of doctors who had been found guilty of research misconduct but gone on to be deans and others in charge of researchers.

Like we have independent investigation, prosecution and courts for criminal cases, we need a similar criminal law with similar independent institutions for medical fraud.

Science is human – and some humans behave badly

Ed Yong discusses human science:

Over the last year, I’ve written several pieces about problems in psychology – namely, an overwhelming skew towards positive results, a lack of replications to check if they are correct, and a disturbing number of cases of misconduct. But of course, psychology is not alone here. These problems are pervasive in science, and it’s important to discuss them.

Publish shoddy study in PNAS, dupe patients, get access to NIH-funds!

CFS Advisory Committee, October 3-4, 2012:
… Dr. Susan Maier (NIH) reported that several new members were added to the Trans-NIH ME/CFS Working Group, including Dr. Harvey Alter. It’s very good news that Dr. Alter is staying involved in CFS despite the end of XMRV. …
(via CO-CURE maillist)

Oh isn't it simply great news that our beloved Harvey Alter, after pushing the shoddy Lo/Alter/XMRV study into PNAS, gets money from the NIH to continue his fabulous work? Dandy, indeed. Simply splendid. A great scientific addition, indeed.

In that spirit, I nominate Marc Hauser, Scott Reuben and Diederik Stapel as new members for the Trans-NIH ME/CFS Working Group – with such outstanding scientists we will know for sure how the NIH-money will be accounted for!

Failed Replications and Fraudulent Researchers – Psychological Research is a "Mess"

Last Wednesday, Nobel laureate Daniel Kahneman sent an email to a group of a dozen or so psychologists telling them that the credibility of their field was in danger. The recipients all worked on social priming – the study of how subtle unconscious cues can influence our behaviour. It’s an area that has attracted controversy of late, due to failed replications of classic results[!], the outing of fraudulent researchers, and a more general concern among psychologists about the validity of their field’s results.

Kahneman meant the email as helpful advice, but his wording couldn’t have been stronger: “Your field is now the poster child for doubts about the integrity of psychological research… I believe that you should collectively do something about this mess.” His solution: a “daisy chain” of replications, where laboratories collaborate to check the results of their neighbours, in an open, transparent, and pre-established way. …

And:

“It doesn’t follow that people who are doing priming are committing fraud; it’s more likely that people who are committing fraud are drawn to that field. It’s important not to invert the logic of that.”

Orac: Andrew Wakefield’s libel suit against Brian Deer: Dismissed!

Orac: Andrew Wakefield’s libel suit against Brian Deer: Dismissed!

Lies, damned lies and Dr. Mikovits

In July, she says, she found it—an entry from March 2009 indicating that a culture of the XMRV virus had been placed into the same incubatorwith the rest of the lab’s blood samples.

http://www.thedailybeast.com/articles/2012/07/23/how-research-into-chronic-fatigue-syndrome-turned-into-an-ugly-fight.print.html

Oh, there was XMRV culture in the WPI-lab, while she did the Lombardi 2009 study? You don't say. That would mean that Gerwyn/V99/Flex (or however his sockpuppets call themselves) is a stupid lying cunt.

Mikovits says she was out of town the day this occurred. 

I am sure that's what she said. Its always the others. Always. A shitstorm of incompetence and conspiracy around her, and Saint Judy is the only person, I tell you, the only person in the world who is gifted and innocent. And it's always her who throws others under the bus speaks up about ethical breeches. Always her.

I still wonder how only the patient samples got contaminated, though. Wasn't it supposed to be a blind study? Or was that another lie by Gerwyn/V99/Flex?

And I deeply wonder why fabrication is the only reasonable explanation I can come up for the results Mikovits reported?

"Institutions are unlikely to fairly investigate allegations of fraud made against their own researchers"

… One point he made was that institutions are unlikely to fairly investigate allegations of fraud made against their own researchers: this obvious point seemed to be new to some people.  …

You don't tell, captain obvious.

… Aldhous explained how a journalist might have to put in as much time to get a story about fraud as to get, say, 75 stories about usual science. From a business perspective, that is obviously a serious problem. …

So Mikovits, Ruscetti and Lombardi can carry on their business – well, Mikovits only if she finds a new job.

Medical Science: Professor steals from Grad Student, gets Nobel Prize

…
A lab notebook belonging to Albert Schatz, left, with his supervisor, Selman A. Waksman, and discovered at Rutgers helps puts to rest a 70-year argument over credit for the Nobel-winning discovery of streptomycin.
…
The 60 boxes contained details of how streptomycin was found — and also of the murky story behind it, a vicious legal battle between Dr. Waksman and his graduate student Albert Schatz over who deserved credit.
…
As word of the discovery spread, reporters flocked to Rutgers to record the amazing event. But in telling and retelling the story, Dr. Waksman slowly began to drop Dr. Schatz’s name and claim sole credit. He also arranged with Rutgers to receive hundreds of thousands of dollars in royalties from the patent that he and Dr. Schatz were awarded; Dr. Schatz received nothing.

… the scientific establishment sided with Dr. Waksman, scolding Dr. Schatz for having the effrontery to challenge his professor. And two years later Dr. Waksman alone was awarded the Nobel Prize for the discovery. Dr. Schatz protested, but the Nobel committee ruled that he was a mere lab assistant working under an eminent scientist. Dr. Schatz disappeared into academic obscurity and died with the full story still untold.
…
http://www.nytimes.com/2012/06/12/science/notebooks-shed-light-on-an-antibiotic-discovery-and-a-mentors-betrayal.html?_r=1