"How evidence-based medicine is failing due to biased trials and selective publication" (Free)

[Dolphin]

Full text free at: http://www.nogracias.eu/wp-content/uploads/2014/05/FALLO-MBE.pdf

I saw James Coyne PhD plug this on Twitter, saying it was even more true of psychotherapy

I haven't read it myself.

How evidence-based medicine is failing due to biased trials and selective publication.


Every-Palmer S, et al.

J Eval Clin Pract. 2014 May 12. doi: 10.1111/jep.12147. [Epub ahead of print]


Affiliation

Abstract

Evidence-based medicine (EBM) was announced in the early 1990s as a 'new paradigm' for improving patient care.

Yet there is currently little evidence that EBM has achieved its aim.

Since its introduction, health care costs have increased while there remains a lack of high-quality evidence suggesting EBM has resulted in substantial population-level health gains.

In this paper we suggest that EBM's potential for improving patients' health care has been thwarted by bias in the choice of hypotheses tested, manipulation of study design and selective publication.

Evidence for these flaws is clearest in industry-funded studies.

We argue EBM's indiscriminate acceptance of industry-generated 'evidence' is akin to letting politicians count their own votes.

Given that most intervention studies are industry funded, this is a serious problem for the overall evidence base.

Clinical decisions based on such evidence are likely to be misinformed, with patients given less effective, harmful or more expensive treatments.

More investment in independent research is urgently required. Independent bodies, informed democratically, need to set research priorities.

We also propose that evidence rating schemes are formally modified so research with conflict of interest bias is explicitly downgraded in value.


© 2014 John Wiley & Sons, Ltd.

PMID 24819404 [PubMed - as supplied by publisher]

 

[alex3619]

I have been arguing the same thing. Its why I keep harping on about Zombie Science. Appointing Peter White to review the CBT/GET area, the next Cochrane report, is just icing on the cake of failure. This is EXACTLY why I am worried about the IOM and P2P. Even if the committees are fair and unbiased, it is likely the evidence they have to draw on is unfair and highly biased. That evidence is being assembled using simplistic evidence ranking criteria. Only having experts on the IOM panel gives it a chance. Sadly this is not the case for the P2P.

PS I like that this paper is freely available. That is good for the debate.

 

[Tired of being sick]

EBM achieved it's aim alright

it is called profit over health

 

[alex3619]

How are biased randomized trials identified when their conclusions are discredited? Bad evidence lingers. Biased randomized trials are not clearly labelled as such once discredited. Once papers enter the electronic literature there they remain. There is no vigilant cyber librarian who stamps ‘retracted’ across them if they are subsequently refuted, and they may continue to mislead. If a busy health prac- titioner does a quick keyword search, the discredited randomized trial may be the first to appear, with no identification of its flaws. Even informed critics may be misled. For example, Tatsioni et al.

found 50% of academic reviews promoted a discredited intervention (vitamin E for heart disease) 5 years after it had been convincingly proven ineffective [62]

This is, I think, a major problem for us.

 

[alex3619]

EBM achieved it's aim alright

it is called profit over health

Actually that is not, technically, EBM, Evidence Based Medicine. Its because EBM has been adopted by the other EBM, or Evidence Based Management, or Evidence Based Medical Management in this case. This is a huge part of the incentive for bias, and why I talk about medical management as promoting Zombie Science.

 

[Tired of being sick]

Any drug that shows any promising results,
they either take it off the market
or monopolize the market
2 immediately comes to mind
which solidifies my point
Ampligen
Xyrem

 

[alex3619]

For example, the Grading of Recommendation Assessment, Development and Evaluation
(GRADE) system allows for upgrading observational evidence demonstrating large effects, and downgrading randomized trials for failing to adequately conceal allocation (and various other factors) [65]

I have made this same point about ME papers. Psychogenic papers have no solid validated evidence for their hypotheses, and rely heavily on subjective outcomes. Subjective outcome papers should be downgraded. Further, the high effect sizes found in many ME papers, particularly to do with the latest biochemical findings, should be upgraded. This would cause a massive shift in any EBM review of ME.

 

[heapsreal]

What i dont understand is that a few good medications that help treat cfs/me would make a tidy profit for a drug company. If profit is a good motivator then one would think they would be jumping at trying to treat us.
I think the repurposing of stimulants with antioxidant/mito supps is a way they are looking at making money from an old drug. I dont think its going to be the answer for many cfsers but im sure some will benefit. It might lead the way for other companies to look into these things, hopefully??

 

[alex3619]

@heapsreal, the trend is to promote new drugs, still on patent, for which exorbitant fees can be charged. Reformulating a drug gives them a new patent, as its a new formulation, and hence a new invention, so they can continue to charge lots. Simply using the old formulation makes them much smaller profits.

 

[heapsreal]

@heapsreal, the trend is to promote new drugs, still on patent, for which exorbitant fees can be charged. Reformulating a drug gives them a new patent, as its a new formulation, and hence a new invention, so they can continue to charge lots. Simply using the old formulation makes them much smaller profits.

Any drugs that helps us is a bonus. the wealthy will be able to afford the meds on patent but eventually these meds do come off their patent and then we can swoop on them, lol. Im hoping it stimulates research into treatments for us. I guess its the reason why we want ampligen approved, it may not help all of us but stimulate further treatments.

Its hard to stimulate a not for profit type treatments and research, unfortunately money is a motivator. Also as we have spoken before, treat cfsme people is a saving for many govts as it can keep people of disability payments and in the work force longer. for us it improves quality of life.

 

[WillowJ]

What i dont understand is that a few good medications that help treat cfs/me would make a tidy profit for a drug company. If profit is a good motivator then one would think they would be jumping at trying to treat us.
I think the repurposing of stimulants with antioxidant/mito supps is a way they are looking at making money from an old drug. I dont think its going to be the answer for many cfsers but im sure some will benefit. It might lead the way for other companies to look into these things, hopefully??

CDER said one reason drug companies have been reluctant to get involved is that it is not clear what marker should be used to show improvement (no one wants to put money into drug development until they know what the rules are for getting approved). Should they measure a cytokine? NK cell function? Stair climbing (maybe via questionnaire)? Something else?

They do not know, and there has not been a guideline until now. CDER is working to improve this, in part by publishing a guideline (draft is here).

 

[heapsreal]

CDER said one reason drug companies have been reluctant to get involved is that it is not clear what marker should be used to show improvement (no one wants to put money into drug development until they know what the rules are for getting approved). Should they measure a cytokine? NK cell function? Stair climbing (maybe via questionnaire)? Something else?

They do not know, and there has not been a guideline until now. CDER is working to improve this, in part by publishing a guideline (draft is here).

your right. even those who improved on rituximab or even ampligen, they dont know how it works? I guess theres a few ways to show if one has improved with say an exercise test/2 day test, maybe a cognitive test etc but these dont really point to a physiological point for companies to target a drug on.

 

[alex3619]

your right. even those who improved on rituximab or even ampligen, they dont know how it works? I guess theres a few ways to show if one has improved with say an exercise test/2 day test, maybe a cognitive test etc but these dont really point to a physiological point for companies to target a drug on.

Yes, we have what are called surrogate endpoints i.e. less than ideal. A drug company that might be willing to invest tens of millions of dollars wants something solid to base their risk on.

 

[heapsreal]

Yes, we have what are called surrogate endpoints i.e. less than ideal. A drug company that might be willing to invest tens of millions of dollars wants something solid to base their risk on.

Also there might not really be an end point. Maybe medicine have to realise that with ME multiple things can be going on so things need to be approved for ME if something arises thats an issue. Example is that valcyte is approved for ME with those who have proven active infections for cmv/hhv6? Ampligen is approved for ME with those with low nk function and other low t-cell function.

Some docs just arent game to give ME patients anything, even antibiotics if there is a possible bacterial issue. I think they need to make it easier for doctors to treat the abnormalities found in ME. Many docs dont realise orthostatic issues are a problem for ME people.

Maybe they need to list all the possible abnormalities/infections found in cfs/me and allow certain drugs to be indicated for this. Again a drug isnt just approved for ME but for those with ME that have xyz. At this stage i dont think they are going to find a one hit wonder but theres plenty of potential top 10 hits that can help us and should be approved for use in cfs/me.

Just being approved for us makes it potentially easier and cheaper to get these treatments, even if its insurance based health care like the USA or a socialist type health care like the UK and australia.

just a thought

 

[SDSue]

Genetics should eventually trump EBM. To claim that any medical intervention is right for the entire population, based on percentages helped in studies, is ignorant.

Just look at MTHFR and folic acid vs folate. How many women were made sick by prenatal vitamins containing folic acid, and were told that they were just being overly-sensitive? Yet still, the only prenatals covered by insurance are those containing folic acid, because decades-old "evidence" and corporate profits don't easily allow for change.

It has been proven that a certain gene variation will cause undesirable responses to the cancer drug irinotecan, and a different gene will determine response to warfarin. Klimas and company have proven that exercise causes abnormal gene expression in ME patients. More and more, genetics are playing a role in deciding care.

Patients have been proven right over and over again. It's a sad state of affairs when doctors no longer listen to their patients, but instead rely on "evidence", however contrived or old, to make decisions. Just because I may be an N=1 doesn't make me wrong. It makes me genetically unique.

Changing mainstream medicine is like turning a ship - and we ME patients don't have the time to wait. We've jumped off board and are swimming in shark infested waters instead.

 

[Tired of being sick]

How many of you know about Monsanto/Pfizer?

 

[Esther12]

I just happened to be skim reading this, and although it focussed a lot on pharmaceutical trials, I thought it seemed good and somewhat relevant, particularly given the funding of PACE.

Their conclusion:

As a result patients may be given less effective, harmful or more expensive treatments. We have proposed some possible remedies, including that the EBM movement explicitly downgrade any research produced by those with a vested interest in the results.

I might try to read it properly later (earlier in the day).