Having it both ways

In earlier critiques of Bad Medicine I’d wondered at the contradiction of regulatory authorities handing down $bn punitive fines for wicked off-label promotion of meds, while sponsoring trials that potentially expand the range of approved conditions and thus the on-label market. Part(3) of this series on pregabalin/Lyrica concludes herewith.

In 2011 the Pharmaceutical Benefits Scheme refused Pfizer a subsidy for Lyrica on the grounds that none of the studies thus far had shown efficacy against neuropathic pain. Just 12 months later, they changed their mind. What new data could have influenced this, when the drug’s ineffectiveness was already the source of a joke on its side-effect of dizziness (Schwindel, translated in German)? Significant adverse events of dizziness and somnolence were manifest at the lowest dosage of 150mg consistently in 38 trials  ‘The adverse event profile of pregabalin: A systematic review and meta-analysis of randomized controlled trials’ (Zaccara & Specchio et al, 2011).

Courtesy of rheumatologist Dr L.Kirsch MD, Jun 2012


This somewhat contradicted Pfizer’s sponsored investigation into Lyrica:  ‘Cognitive effects of pregabalin in healthy volunteers’  (Stalinsky, Storzbach & Muniz 2009) offering a conclusion of “… negative cognitive effects and neurotoxicity complaints”. The drug only works (wirksam) to relieve pain at larger doses, at which point there’s been an exponential increase in Schwindel.

Pfizer’s 2012 re-submission to PBAC had two new studies; Boyle, Gribble & Johnsen et al , finding “…there was a significantly higher number of adverse events in the pregabalin treatment group. Conclusions: There was no significant difference in analgesic efficacy between amitriptyline, duloxetine and pregabalin.“, and Trial 1107 – an unpublished, internal study run by Pfizer. I’ll repeat that. The former showed no superiority of the med over amitriptyline, a 50 year-old mainstay known as Endep, furthermore it had worse side-effects. And the in house report …. one can only hope that it was run with more probity that their Trovan trial, best described as a crime against humanity. In summary – this one piece of evidence, from behind closed doors, sufficed to allow “The PBAC recommended an Authority Required (Streamlined) listing of pregabalin (all strengths) for the treatment of refractory neuropathic pain not controlled by other drugs on the basis of acceptable cost-effectiveness compared with placebo in patients dissatisfied with their current pain relief.

There was another study submitted to PBAC, a comparison showing pregabalin as better than amitriptyline in cancer pain. At a dose of 600mg – at which point conscious state is altered.

What else changed from 2011? Dr Suzanne Hill, co-editor of ‘Evaluating Pharmaceuticals for Health Policy and Reimbursement’ *, was appointed chair of PBAC. This went down well with the pharmaceutical industry. She’s since returned to WHO in the Expert Committee on the Selection and Use of Essential Medicines , replaced with Prof Andrew Wilson per command of Health Min Sussan Ley – who’s been recently forced to resign due to misconduct. I have no idea if governance has improved, nor can inform as to whether it ever existed.

The drug really didn’t work. The 2012 NHMRC grants round allocated $0.62m (plus topups) to try Lyrica for sciatica – leg pain from back nerve damage. Last month PRECISE’s results were posted: no benefit over placebo, and 40% reported the adverse side-effect of Schwindel. Pfizer still won though – they didn’t have to pay for the study. In the interim, the musculoskeletal team of experts had railed against alternative approaches such as imaging – although that’s done with a view to inspecting the problem source for potential intervention at the site. Dr Hill’s colleague at WHO, Prof Lisa Bero didn’t ever respond to concerned memos regarding the probity of PRECISE, nor to complaints about the Monash/NHMRC cases of misconduct.

On the one hand, we trust pharma to do the studies, and on the other, we fund universities to do the studies on their behalf. Win, win for the industry.

*Page 37: “There is evidence that the research methods of trials sponsored by drug companies are at least as good as the trials sponsored by public resources, and in many cases they are better“, referencing Bero – “Study design in drug company sponsored clinical trials better than in research where no stated sponsorship”  in her thoughts. My opinion is that trial 1107 should publicly release the names of researchers, or am I asking too much? They’re kept secret, and bound by confidentiality, per NCT00407745: “There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI’s rights to discuss or publish trial results”.



Healthy participants volunteering to receive first-in-human safety trials of a drug are well compensated, and receive round the clock monitoring. But sick persons opting into an experimental program pay to exploit a legal loophole, and there’s no oversight. This truly exemplifies survival of the fittest.

Drugs are priced by preparedness to pay.

Drugs are priced by preparedness to pay.

A doctor, accused of administering banned substance Thymosin beta 4 (TB4) to footballers, was exonerated by the Medical Board in June of trying out etanercept on stroke patients. This genetically-engineered bioagent is the subject of an earlier blog , and is a last resort in arthritis. It trades improved Quality of Life, for reduced Quantity. This is a moral decision, but one informed by solid clinical evidence of the risks vs benefits of blocking autoimmune responses. The AHPRA letter declares that his “… decision to use etanercept was based on high-quality evidence. All patients were informed before attending and fully understood the position in Australia…”,  and ends with an apology for the stress of their investigation. The doctor wrote in his defence that “Griffith Uni was in the process of doing clinical trials with the drug“. Uhh, no. Dr Rick Williams has approval only for his trial protocol, but insufficient funding to begin. This footage from 60Minutes is the only ‘proof’ of efficacy:

Clinical notes show that patients were informed that this would cost $6k in Florida. So a vulnerable person was injected on the basis of pricepoint. Some had also signed off on a 29 point consent form, which includes unspecified “immune stimulating injections”. I have no idea how such conduct can be condoned, but it is indeed compliant with the Good Medical Practice Code-of-Conduct Sn2.2.6. Providing treatment options based on the best available information. With no definition of what constitutes an evidence base, misconduct is unfettered. Snake-oil salesman Dr Tobinick had been challenged to support a clinical trial, but sued detractors instead – a case thrown out by the US District Court 30 Sept 2015.

The doctor presented at a Florida conference in 2015: “Thymosin beta-4 affects immune responses and is integral to formation of growth of normal tissue when damage has occurred rather than the chaotic formation of scar tissue that normally happens.” and his Aust website states: “Peptides such as AOD 9604, Thymosin beta-4 and Follistatin are peptides … Agewell is a world leader in the use of these medications.” The TGA site is more enlightening: “These substances are currently used illicitly to enhance sporting performance and more broadly across the community often for body building and image enhancement purposes…

  • No form of Thymosin Beta 4 is yet approved for human therapeutic use anywhere in the world.
  • The medications are considered experimental in humans, with potential side effects including carcinogenicity and cardiovascular problems.”
Injecting room at HyperMed

Compounded concoction in the injecting room at HyperMed

But they’re still legal, with the doctor’s scrip. Which doesn’t even require a consultation, as an order from Peptide Clinics demonstrates. Fairfax’s sports journalist Jon Pierik and crime reporter Cam Houston were shown evidence of all this a month ago, but only wanted to know whether celebrity sports stars were implicated. Or had I seen any bikies? The consumer is left uninformed, and quite unprotected by regulatory authorities.

Stephen Dank administered peptides to rugby player Jon Mannah, who had been in remission from cancer but then died in 2013 after relapse. Dankenstein sued the Daily Telegraph for claiming that he had a case to answer for manslaughter, and the Supreme court agreed with the paper – dismissing the defamation complaint. No charges have yet been laid however, there’s uncertainty over the drug used. In April of this year, a peptides patient died suddenly, but there’s more chance of prosecution since TB4 is written in clinical records. Nonetheless, the Crown hasn’t yet taken action after 7 months – so perhaps it’ll suffice to blame the victims, rather than the perpetrators? That’s what the Essendon players discovered.

I recently lodged formal complaint to AHPRA over the disparaging statement by a guest Professor on radio “… holistic nature of alternative medicine albeit not evidence based … alter some of the biological behaviour in an adverse fashion, but that’s not out there in the public, so people who spruik these things may get away with it“. This was dismissed since the Private & Confidential letter states: “It cannot be concluded that these comments unreasonably reduce confidence in the therapy, as it is reasonable for Prof XXX to proffer this opinion“. That’s what I’d spent several months attempting to obtain directly, an admission that his ‘opinion’ had no supportive facts whatsoever, and indeed the therapy has a substantial gold-standard evidence base (used in cancer support at the Alfred Hospital). The man is a great oncologist (albeit one ignorant about complementary therapies), so I won’t further his embarrassment with naming. Doctors’ unfounded ideas are taken as advice from the Oracle, even justifying deadly human experimentation, but complaints are dealt with in secret and there’s no rights to appeal.

It’s a dog eat dog world. Some are rabid.


Endemic corruption within medical research is of no concern to government, since the issues previously raised have been put to Health Ministers and even to PM Turnbull. Without a response. Few have the integrity to whistleblow, due to lack of both regulatory authority and legal protection. After all, there’d be no shortage of backfill for your position upon dismissal from the increasing numbers of vulnerable foreign workers on tenure of a temporary visa. The blue bar charted shows post-docs, paid the same as a burger-flipper while Australia trains them in our wily ways. Employment Minister Eric Abetz denied existence of this scam in correspondence of 16th Sep ’15, despite a University advising “The Department of Immigration and Border Protection has limited the value of the living assistance which can be provided by the University to subclass 402 – research stream visa holders. The maximum contribution by the University to living expenses is approximately $34,000 per annum (at October 2012); this amount may alter on an annual basis.


Report BR0169

This matter has been raised with Immigration Minister Peter Dutton several times, but the office has never responded. Wouldn’t he be concerned about history judging him harshly, should the truth ever come out regarding misconduct? Uhh, no. Already looking at a pension of 1/6th of a million dollars annually, that means his CV needn’t be without a fault or three. Even if it’s already blemished by his  previous portfolio as Health Minister resulting in his poll ‘win’ from Australian Doctor magazine as being the worst performer in its 35 year history. No remorse at that failure either – last months confrontation with doctors of Lady Cilento childrens hospital showed his contempt for human rights also.
Your vote comes with no guarantee of governance, as there’s no accountability for policy made up on the fly. President of the amoral AMA turned politician, Dr Brendan Nelson, surprised both the Air Force and Defence Materiel by purchasing $7bn in Super Hornets from ex-parliamentary colleague Andrew Peacock, then a Boeing salesman. “It just flawed me … there was no independent analysis,” recalls AVM Peter Criss, a retired Air Commander of Australia. John Howard approved the suggestion in 2006 without seeking expert opinion, and far from showing remorse for events as they’ve unfolded is instead reveling in regularly being voted Australia’s best PM by Murdoch press conducted polls. That’s despite being outed as a liar regarding ‘children overboard’ by Admiral (rtd) Ritchie, onetime Chief of Navy.

The first planes were delivered in 2010, but six years later we’re still investing heavily in a future around the Joint Strike Fighters (JSF). That’s a project we’d supported by pre-purchasing 100, but both the budget and time were wasted during the cocaine-fuelled ‘nought-ies’ (the era which led to the GFC). Both aircraft are already outclassed by the Russian SU-30 & 35s purchased by five SE-Asian neighbours. “This thing [Super Hornet] will not survive in a fight now in our region,” says Criss. While the JSF struggles to achieve operational readiness, the SU ‘Flanker’ continues to evolve.

Photo courtesy LAC/W (RAAF) Kim Eager Sarah McLeod from the Ducati team with Dr Brendan Nelson. Minister for Defence Dr Brendan Nelson launched the Defence Motorcycle Awareness Campaign at the Sutton Road DriverTraining Centre, ACT near Queanbeyan on the 4th August, 2006.

Photo courtesy LAC/w (RAAF) Kim Eager
Sarah McLeod with ‘Top Gun’ Dr Brendan Nelson on the 4th August, 2006.

If Brendan ‘need for speed’ Nelson didn’t know what he was doing (he dropped out of his economics degree), nor do we know what they’re thinking. There’s a Senate inquiry into the JSF concluding in May 2016, but a previous report is pertinent “… the arguments are of a highly technical nature and much of the data necessary to form an understanding of the performance of the JSF is classified and not available for public scrutiny“.  The quid pro quo of political understandings with business here doesn’t work so well strategically however. Regardless of commitments to JSF, or however many M1A1 battle tanks Howard purchased, it’s been made crystal clear that our new “best friends” are Japan. Regional instability as a consequence of South China Sea conflict won’t be America’s problem, even if they are the trigger.

The secrecy that allows medical research to fester is the cause of the problem here, too. Any misconduct in national affairs remains secret, and public servants intending to whistleblow should pay heed to Sn 70(2) of the Crimes Act, 1914: A person who, having been a Commonwealth officer, publishes or communicates, without lawful authority or excuse (proof whereof shall lie upon him), any fact or document which came to his knowledge, or into his possession, by virtue of his office, and which, at the time when he ceased to be a Commonwealth officer, it was his duty not to disclose, shall be guilty of an offence.
 Penalty: Imprisonment for two years.

The USA, on the other hand, rewards with a payment up to 10% of the public monies recovered.

Rage, rage against the dying of the light

… from ‘Do not go gentle into that good night’, Dylan Thomas




Before delving into the massive NHMRC research investment of public money  ($5.1m upfront) into Pfizer’s Lipitor that is STAREE, some preliminaries:

Few Australians would be unaware of the furore raised by Catalyst (The Heart of the Matter), and subsequent retraction by ABC management of the program. A couple of opinions on Dr Demasi’s journalism by Drs Briffa and Coleman, and their arguing in blog comments shows that even those in general agreement were discordant. Instead of ‘playing the ball’ and take on the well-orchestrated industry, I’ll ‘play the man’ and focus upon individual proponents of statin therapy. And their complicity. It’s a softer target due to a weakness in humanity – insatiable need for funding.
Heart Foundation CEO Jen Johns immediately warned that sales of statins would be harmed, and a month later they published a poll by their Rob Grenfell showing 10% had stopped the therapy. Their corruption is further detailed at this update, and is unsurprising given that the decade-long president is father of Pfizer’s lobbyist Andy Thirlwell. Even before the exposé aired, Prof Emily Banks had pointed the bone * thus: “It’s likely that if this program goes ahead, and it does the unwarranted undermining of statins, that there will be people who didn’t have to have a heart attack and didn’t have to die from a heart attack, who will die through reducing use of statins“. An expert in this field, having authored ‘Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality’, she’d be appreciative of Pfizer’s infamous blue pills for ED. Dr Grenfell concurs with a warning, “These results tell us that every man who is suffering from any degree of erectile dysfunction should be seeking medical assistance as early as possible“.

Grenfell and Tonkin et al wrote of the confusion in lipid management in May 2015 ‘Clinical Guidelines on Hyperlipidaemia: Recent Developments, Future Challenges and the Need for an Australian Review’ – considering the perspective of the American Heart Association “… the maximum tolerated dose of a statin be generally employed”, but their own concern is absence of an optimal target level: “Whilst the cost-benefit analysis of statin therapy is generally favourable, it is very sensitive to the absolute risk level of the patients selected for therapy”. Andrew Tonkin had already made his mind up in 2005 though, as chair of the Heart Foundation’s consensus Position Statement on Lipid Management a number of guidelines and criteria are given to prescribers. Along with a conflict-of-interest declaration. The same “provision of consulting services to Pfizer” should also have been disclosed in a JAMA report ‘Association of LDL Cholesterol…with Risk of Cardiovascular Events Among Patients Treated With Statins’, that was subsequently amended due to medico complaints to the journal.

Bias is a relevant fact in STAREE (STAtins for Reducing Events in the Elderly), but frequently missing. Monash colleague Sophia Zoungas should also have declared a 2007 Pfizer personal grant of $55k in articles such as ‘Treatment of Dyslipidemia and Cardiovascular Outcomes: The Journey So Far—Is This the End for Statins(?)’ advocating “the first [Randomised Controlled Trial] to determine the effects of statin therapy vs. placebo in an apparently healthy elderly cohort living independently” ie preventative Lipitor for the over 70s. This is not however, a trial designed to test a hypothesis. It’s an experiment on the elderly to see what happens. Lipitor is the hammer, let’s see if it nails aging! Extending of life is the outcome being investigated – meaning that if they’re wrong, then shortening of life may become apparent.  A successful trial is assured, since my previous example from this department shows an outcome can be invented with impunity. And worsened death rates ‘adjusted for’.

One example of deception is apparent already. In July ’14 Current Opinion in Cardiology neither professor mentions Pfizer’s backing, but offer panacea in claiming: “In a meta-analysis of observational studies, statin therapy was associated with reduction in risk of dementia, Alzheimer’s disease and mild cognitive impairment“. The cited references of Richardson et al (in response to the Lipitor label warning of additional risks, imposed by the FDA in 2012): “Published data do not suggest an adverse effect of statins on cognition.  The strength of available evidence is limited…” and a Cochrane review by McGuinness et al : “Demonstrated lack of benefit of statins compared with placebo on cognitive measures” actually contradict this claim! These issues were raised with Monash Chancellor Finkel, but the reply from his Director, Tony Calder abdicates responsibility: “The matters you allude to in your email are matters that are dealt with by University management therefore the Chancellor, as head of Council, will not be providing a response to your email.

Solving the problem of an aging population?

Solving the problem of an aging population?

Two years after Catalyst aired, a Med Jnl of Aust article advises that over the first eight months 61,000 have made up their own, negative opinion of the meds: “…changes in statin use occurred despite warnings in the Catalyst program that its content should not be taken as medical advice”. Co-author Sallie-Anne Pearson is noncommittal on consequence, having just published a study that concludes: “Deprescribing of statins may be indicated for some older people, because the evidence for benefit in primary prevention of cardiovascular disease is limited and there is an increased risk of side effects in old age.” Other, collaborative colleagues are more determined to restore Lipitor to its heyday position of the highest grossing drug. That popularity arose due to trial results on a surrogate outcome of LDL (Low Density Lipid) levels, without epidemiology data as to whether the drug improves survival rates in the community. We’re a trusting lot.

On the other hand the Brits stay true to form, by constant whinging about risks: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714436/ 😉

* Indigenous Australian’s forewarning of death as punishment

Manipulating the market.

Once upon a time, doctors were hanged for unethical human experimentation. Of 16 found guilty of war crimes, 7 were executed by hanging. Nuremberg, then Helsinki, countless other, and most recently the 2010 Singapore Statement on research ethics have convinced us that society has matured. But humanity hasn’t evolved, and the same Hippocratic oath persists.hangedDr

The forthcoming ‘Handbook of Academic Integrity’ has a chapter by Prof Vaux, whose accusation of misconduct against Uni of NSW researcher Levon Khachigian led to his standdown in 2013. That team had received $8.3m in a 2014 cardiovascular grant from NHMRC. The UNSW has just last month cleared Prof Khachigian of all charges, since: ….” breaches were the result of Professor Khachigian’s genuine error or honest oversight, not deliberate or intentional conduct.” The sacked whistleblower who brought the scandal to public attention, Dr Ying Morgan, wasn’t interviewed or requested to make a submission to the confidential inquiry. This was a case of fabricated data, whilst my previous post blogged how un-tampered data can be described howsoever as the study author chooses in order to suit their intent. Then there’s statistical adjustments.

David Vaux quotes Stanford biostatistician Prof Ioannidis, who finds procedural errors interpreting data in the majority of trial reports i.e. most studies are falsely presented. The figure given is 90%, which would mean that only 1 in 10 regulatory approved meds are truly beneficial. Deliberate obfuscation of harm also occurs, and Peter Gotzsche or David Healy are worth reading. The tutorial given at Monash in the Advanced Statistical Methods for Clinical Research subject MPH5270, on how to coverup dozens of deaths in a trial gone awry has already been discussed here . This post moves on from the blatant misconduct, to the insidious – market analysts determining what treatment you can receive.

Naltrexone blocks opioid receptors, and is approved to treat substance abuse. In 1985 Dr Bihari found that a one-tenth strength dose improved survival in HIV and postulated that the body’s endorphins were being boosted. Prof Mark Hutchinson and a team determined in 2009 that a similar molecule, naloxone alleviated chronic neuropathic pain by suppressing neural immune response to a perceived allergen attack, which has relevance in MS, fibromyalgia, Traumatic Brain Injury, and other inflammatory cytokine conditions. This led to Prof Jarred Younger of Stanford Uni trialing Lowdose Naltrexone (LdN) successfully in fibro, using a gold-standard randomised crossover protocol. The FDA didn’t accept the evidence as warranting their approval, and independent researcher budgets were never going to be able to satisfy their demands. A state of play report is available from this open-access rheumatology journal, and rheumatologist Emma Guymer visited their lab. But then reportedly told an LdN advocate that she couldn’t prescribe “for contractual reasons”. Buyers clubs solve this roadblock. There is a growing, loyal online community procuring LdN by either doctors scrip and a compounding pharmacy, or import from Canadian or Israeli sources. This established market seemingly deserves support by US insurance company rebate or else Australian PBS subsidy, so pfarma was approached to start the approval process.
Bristol Myers Squibb held the original patent for Revia/naltrexone, and after deliberating on the request for five months their Medical Director Marian Gandy determined there to be no opportunity: “I have explored the options with our global teams who determine the development programs for our products and regret to inform you that there are no plans to seek any further indications for ReVia“.

Bad drugs are pushed, good drugs are withheld. The system is so broken that suggested reforms, such as voluntary conflict-of-interest declarations, can only ever be window-dressing. That’s right – disclosing commercial allegiance is opt-in, since Australia has no equivalent to the US Sunshine Act. Nor an Office of Research Integrity where Dr Morgan could present her allegations. Because as PM Abbott said, “We’re open for business”.

Your life in their hands

An expression often applied to surgery, but physicians playing God is equally relevant to manipulation by mental health practitioners. Except that it’s Quality of Life that’s at stake. Institutions once committed difficult persons, but today medicating provides that confinement. Mostly beneficial in mental illness, mostly harmful otherwise.

So drawing the line for treatment carries grave responsibility. Complaints of this example of insitutional malpractice I detail here have however, been dismissed by  all governance authorities. In concluding that “Mental health is associated with changes in foot pain. Clinicians dealing with this population should consider the contribution of mental health in their management and treatment of foot pain” the connection is made – unless pain improves, it’s psych. The final page emphasizes the viewpoint, “the results from this current study suggest that foot pain could be related to mental health in the same manner as other chronic musculoskeletal conditions“. *
Except that the author’s data shows no significant association.
The report linked contains an untruth. Table 1 shows that mental health isn’t the factor – but rather it’s Vitality , or energy, which is determinant of recovery. The difference of 12 points equates to an increased likelihood of inability to work due to fatigue of over 60%, according to one validation of the SF-36 (Quality of Life) Vitality scale. Limitations of a self-report survey in judging someone to be suffering mental illness aside, this is a fabricated conclusion. And one which suits the purposes of the Professors in their subsequent trial of an anti-depressant in treating arthritis. This is no maverick opinion – Anita Wluka is musculoskeletal editor for BioMedCentral, and her department hosts the musculoskeletal group for the Cochrane Collaboration. It’s not a typo, else the ‘corresponding’ author would acknowledge the error. Nor did the editor of Arthritis Care & Research care to reply, indeed there appears to be no integrity underpinning the evidence base used by every doctor. The university ethics committee overseeing the study answered my challenge but only after four months had lapsed and I’d been suspended by the Dean, for causing distress to these academics by my complaints. Designated integrity advisor Prof Stephen Holdsworth hasn’t responded.

The misconduct isn’t confined to Monash either, Melbourne University obesity expert Joey ‘Mr Big’ Proietto contributed to the study, so their ethics committee was questioned. The only response was: “Due to the [Business Improvement Program] restructure which resulted in this office losing staff we are unable to reply to your request immediately. We will endeavour to respond as soon as possible. Thank you for your understanding“.

 The study was jointly funded by National Health and Medical Research Council and the Royal Aust College of Physicians. NHMRC Director of Grants Saraid Billiards isn’t fussed by misconduct within her alma mater: “we would anticipate that the institution would manage the allegation of research misconduct in accordance with Part B of the Code “. Rheumatology Assigner Academy and coincidentally co-author Prof Flavia Cicuttini could have taken this handpass, but perhaps too busy allocating funds and simultaneously consuming same? RACP “… has rigorous application, review and reporting procedures to ensure a fair and equitable process. …. but the College does not enter into correspondence regarding its decisions.”, according to research manager Laina De Winne. Spokesperson for federal Treasurer Hockey is concerned at budgetary drain, but “As this matter falls directly into the portfolio responsibilities of the Minister for Health the Hon Sussan Ley, Mr Hockey has asked me to refer this matter through to the Minister for her attention.” Joe’s been sent offshore, as our Govt does with many other children of refugees. Office of shadow Health Minister Cath King informs me that the complaint system is working: “Should you wish to pursue your concerns relating to potential conflicts of interest in the grants application process for NHMRC funding, I would encourage you to raise them with NHMRC directly .”

Evidence-based medicine Prof Paul Glasziou is overwhelmed by the extent of fraud: “Good luck with pursuing this. As I now focus on NON-drug interventions and the overall waste in research processes, I no longer get involved in individual problems in drugs research (as that would consume 10,000% of my time!)“. Adjunct Prof Ken Harvey of Medreach agrees, “As Paul Glasziou noted, it is difficult for those of us concerned about such matters to take up every case. The same, regrettably, applies to NH&MRC and University research and governance bodies although you certainly deserve a reply.” He suggested writing to the publishing journal editor, something attempted thrice without response. “Oh dear“, said Ken.

Members of the team are now collaborating with Mandana Nikpour and Andrew Tonkin on a trial of atorvastatin for arthritis, OAKS. Lipitor remains the world’s highest grossing drug on record, and Pfizer quite generous in granting early career kickstarts of $50-55,000. Mandy’s shy regarding her CardioVascularLipids grant, since it’s not declared in an article with Prof Rachelle Buchbinder ‘Should patients with systemic sclerosis-related pulmonary arterial hypertension be anticoagulated?’ (Internal Medicine Jnl of May 2013 ) even though Pfizer’s apixaban is suggested and a favourable result from her registered trial ACTRN12614000418673 will boost sales of their Eliquis. Again as with pregabalin/Lyrica trial PRECISE, NHMRC sponsored.

Arguably harmful except in the population who’ve already had a heart attack or angina, statins have one certain side effect. Fatigue. Which perpetuates the arthritic pain cycle, but Anita wasn’t going to tell you that. Pharmacology and rheumatology are bedfellows who’re profitable partners.

* Copyright © 2014 by the American College of Rheumatology

Fibromyalgia appears destined to remain the elephant in the room if this month’s Rheumatology edition of Australian Family Physician is anything to go by – not a mention of it. So what do healthcare specialists offer? In 2006 Drs Littlejohn and Guymer published, through their work as Monash Director of Rheumatology and trainee respectively “Fibromyalgia Syndrome: Which Antidepressant Drug Should We Choose”. Linking their Medical Centre with the University seems a worthy approach so as to redress physician misconceptions  – indeed, shortly thereafter the Journal of Clinical Rheumatology published a survey of Southeast Asian rheumatologists. 87% of them believed fibromyalgia incorporated aspects of psychological illness and only 40% of those associated with an institution reported inclusion of FM in their undergraduate training.

Dr Littlejohn then contributed to the 2009 yearlong study on effectiveness of duloxetine/Cymbalta led by Eli-Lilly employee Amy Chappell, which was discredited by exclusion on quality grounds from the independent Cochrane musculoskeletal group’s systematic review of studies on SNRIs . Their supposedly * impartial conclusion drawing upon another five, unbiased assessments was that 10% more people reported significantly reduced pain with duloxetine than those duped by a placebo, however another 9% discontinued treatment due to side-effects. Withdrawal in itself is harmful, the US FDA has published a safety advisory for Cymbalta Discontinuance Syndrome. Agreements posted in 32,000 blogs are somewhat alarming! Any benefits obtained are ‘figure-atively’ outweighed by weightgain reducing propensity to exercise, consensus being that moderate exercise is beneficial for fibro.

2009 was a bad year for pharma. Eli-Lilly pleaded guilty to illegal marketing of anti-psychotic drug Zalprexa for off-label use, and was fined $1.4bn. A recent out-of-court settlement was made with the family of a boy who suicided whilst on Cymbalta, whose claim being that another suicide during drug trials should have prompted warnings.  And Pfizer paid a record $2.3bn for fraudulent marketing of painkillers, including Lyrica. Nonetheless these two medications remain highly profitable with an estimated $18bn in sales in 2012…. which trivialises the settlement for $43m with US attorneys generals that year for once again marketing Lyrica other than for an approved purpose. With such monetary power, when federal NHMRC funding was approved for only 17% of applications for 2014 is it any wonder that Littlejohn and Guymer are reliant on consultancy fees paid by  Eli-Lilly and Pfizer declared (inconsistently*) under their conflicts of interest? “The medical profession—in the US, Europe, and beyond—remains heavily reliant on industry funded continual medical education, and many doctors have accepted substantial hospitality and consultancy fees. Very few have been prosecuted. Disclosure remains patchy and inconsistent. Yet it is their decisions that ultimately determine if medicines are reaching patients for whom they are not suitable. If drug companies need to change their attitude, so do prescribers“. Andrew Jack, Financial Times correspondent writing in the BMJ July 2012.

Evidence update: Two books elaborate these concerns from a practitioner’s perspective. Dr Ben Goldacre’s ‘Bad Pharma’ and leader of the Nordic Cochrane Centre, Prof Peter Gøtzsche’s ‘Deadly Medicines and Organised Crime: How Big Pharma Has Corrupted Healthcare’. Peter’s alarmist chapter title: ‘Very few patients benefit from the drugs they take’  explains that “… apart from such scientific misconduct, insufficient blinding can also make us believe that ineffective drugs are effective.” In damning the exalted gold-standard comparison – the randomised control trial, he warns of assessor bias if they’re aware to whom they gave placebo. To give weight to this claim that doctors lie, his colleague Asbjørn Hróbjartsson is cited … the effect was exaggerated by 36% when evaluated by nonblinded observers. Wow, this Cochrane review ‘Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors.’ needs a read. Ooops, the title omits the keyword ‘subjective’, and 71% of the studies were surgery or the like. cochraneFigure 1 meta-analysis shows that two weighty transmyocardial laser revascularisation outcome reports by Oesterle et al and Burkhoff et al dragged the conclusion from one of no significant difference to a non-blinded bias Odds Ratio of 0.64! So, if you ask F.I.G.J.A.M. whether they THINK the patient’s angina has improved recently, there’s a leaning towards affirmation if they’re aware that surgery has been done? Cardiologists genuinely believing that their interventions are beneficial can hardly be extrapolated to mandating that all trials must be blinded in order to avoid falsification of data, but that’s what’s happened. Peter’s Mentalaz speaking tour claimed that all anti-depressants were ineffective – arguing that severe side-effects results in unblinding. And the effect size was typically <36%, whereby he proves all benefit of the med resulted from bias! And these are the watchdogs? When Cochrane’s doctors stretch the truth about the 36% shift in truth by other research doctors, they’re all damned.
 infinityCochrane pioneers Gotzsche and Chalmers are much alike in their evidence fudging. The Handbook warns  that sneaky research doctors will try to break the blind and fudge the facts. The last para of ‘Rationale for concern about bias’ cites a study by Schultz, Altman, and Sir Iain Chalmers et al in Feb 1995 JAMA. Just one review, covering studies particular to pregnancy & childbirth actually contradicts their own argument: “Trials with inadequate sequence generation yielded estimates of treatment effects that were similar to those derived from trials with adequate sequence generation, after adjusting for the other three methodological dimensions”. But on pg410 a subgroup analysis limited to those trials reporting adequate allocate concealment only managed to find a statistically insignificant p=0.07 (ie close, but no cigar) exaggeration in effect size as a result of poor sequence generation.

This cracks me up. That’s a negative outcome elsewhere than the Cochrane Collaboration, and it relied upon data dredging to obtain a semi-significant conclusion. But it underpins one of their criteria for downgrade of all studies – sanctimonious dogma used thereafter in box-ticking exercises, which actually detracts from quality analysis of evidence trustworthiness. This recalls the classical Ouroboros, the snake eating itself – as a symbol of perpetuation.
*Aust Family Physician Oct 2013: “Competing interests: None”

<Jan 2016 update: an Austrian survey found 89% of GPs would refer fibromyalgia to a rheumatologist, but only 12% of those wanted to treat the patient. With great neuro research nearby by Uçeyler, Sommer & Hauser you’d hope for more than just a handpass: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0146149 >