In recent times there has been a raft of major medical scandals involving false and misleading evidence around the safety and effectiveness of certain drugs – evidence that has undoubtedly led to tens of thousands of unnecessary deaths. Individuals who have dared reveal the truth have been discredited, bullied, and fired, and it has been rare for any individuals complicit in the deceptive science to be called to account.

But in an unprecedented case, the General Medical Council (GMC), the UK doctors’ registration body, is  investigating influential Dr Richard Eastell in early November over the ghostwriting of a study of the drug Actonel conducted by Sheffield University for Procter and Gamble Pharmaceuticals . This case may well be the first time that a professional regulator of doctors has had to deal in public with a highly regarded doctor over whether doctors can and should be involved in fronting manipulated research for industry. But whether it will involve that, and whether it will be honest, remains to be seen.

In 2005 Dr Aubrey Blumsohn publicly raised concerns about the osteoporosis drug Actonel, and the way in which Procter and Gamble had controlled a series of studies at his University, the University of Sheffield. Proctor and Gamble provided millions of pounds of funding for the University and senior academic and osteoporosis authority Dr Richard Eastell in turn signed off ghost written papers that he was unable to verify, allowing wrong information about their drug Actonel to be published. The two papers Blumsohn was supposed to “write” were never published except as meeting abstracts because he didn’t agree to it.  Read more:

Eastell continues to enjoy celebrity status in the osteoporosis field, his name  appearing on numerous industry pharmaceutical papers. But Dr Blumsohn’s career as an osteoporosis authority and his position at the university are over because he refused the use of his name and exposed the truth.

It may look as though justice is about to be done. But chances of the investigation pursuing the truth and restoring Dr Blumsohn¹s reputation are minimal. Eastell is a powerful academic with powerful friends, and the GMC will have its eye on the investment interests of the profession, and the usual business of research at medical schools desperate for cash and the personal wealth of the “key opinion leaders” who have led medicine and science along the path of prostitution.

The involvement of doctors in helping companies to manipulate the pharmaceutical literature is the most important problem in medicine right now. Medical professional regulators like the GMC have failed to deal with the problem in any way despite their claims to uphold the welfare and interests of patients.

If the GMC fails to deal with this justly, the widespread practice of ghostwriting and more importantly of blind academic fronting of company statistics will receive a huge boost from a government body that is supposed to protect patients. The huge implications it has for patients will continue, and more principled academics like Dr Blumsohn will suffer the same injustice if they are brave enough to let us, the pill taking public, know what happens behind closed doors. There will be few academics willing to raise problems in the future, and we will all be a little more unsafe.

Have your say – demand a full and fair investigation : write to the GMC at  email: practise@gmc-uk.org  website: http://www.gmc-uk.org/index.asp

The WHI trial results of 2002 concluded that the risks of using HRT outweighed the benefits. But industry had too much to lose. Like the contraceptive pill, hormone replacement therapy was one of the biggest money spinners of all time and history had shown that healthy older women are a target group easily convinced.  So as the years have gone by the risks of cancer heart attack and stroke have been downplayed and the possible benefits to bone and menopause management enthusiastically revisited. Although many women have stopped using HRT, some have continued and others returned, reassured by their doctors that the risks are minimal.

But the damning evidence keeps coming…

Further analysis of the WHI trial has found that taking combined oestrogen plus progestin longer than 5-years nearly doubles subsequent breast cancer risk each year. [i]  And among current smokers using combined HRT there was an increased risk for death from non-small-cell lung cancer. It was reported that 1 in 100 current smokers experienced an avoidable death during the 8 years of the study. The death rate among women who had been most regular with their HRT during the trial was 53 percent higher in the hormone group than in the placebo group. [ii]

A Dutch study published in February 2009 found that women taking HRT for more than six months at a time are twice as likely to have a malignant melanoma. The investigation, one of the largest ever carried out on oestrogen use and malignant melanomas, found a sharp increase in risk.[iii]

A study published in the journal Cancer in March 2009 reports that breast cancer risk increases steadily during the first three years of hormone therapy and the combination of oestrogen and progesterone is the HRT regimen most likely to be the source of that danger.[iv]   In addition, women who used oestrogen for 10 years or longer had a 50 percent increase in risk of invasive lobular breast cancer.

A Nationwide Danish prospective cohort study published in the Journal of the American Medical Association in July 2009 concluded that regardless of the duration of use, the formulation oestrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk for ovarian cancer. [v]

More dodgy science

Physicians rely on medical literature to keep abreast of safety profiles. A colleague’s name on a peer-reviewed article gives confidence when making prescribing decisions. But it has come to light that over several years Wyeth pharmaceuticals hired medical ghost-writers to create favourable articles about HRT that would later add the name of a reputable physician, giving the appearance that they were the writer. A New York Times article ‘Medical Papers by Ghostwriters Pushed Therapy’ of August 4^th  documents the practice which is also known to be used by other pharmaceutical companies.  Earlier this year it came to light that Merck went so far as to create a fake medical journal called The Australasian Journal of Bone and Joint Medicine in order to promote Vioxx and Fosamax.  World osteoporosis authorities were named on the editorial board, giving great credibility to what was nothing but a marketing tool. Unsuspecting doctors receiving the literature would be hard pushed to see through the deception.

[ii] Chlebowski RT, Schwartz A, Wakelee H, et al. Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women’s Health Initiative randomized clinical trial. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA1500.

[iii] Koomen ER, et al Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study. Annals of Oncology. 2009 Feb;20(2):358-64. Epub 2008 Aug 25

[iv] Calle EE, et al. Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype Cancer  2009; 115. http://www.medpagetoday.com/OBGYN/HRT/12709

[v] Mørch L.S., et al, Hormone Therapy and Ovarian Cancer JAMA. 2009;302(3):298-305

Not a happy new year so far for Merck pharmaceuticals with a swathe of damning reports on their osteoporosis drug Fosamax appearing on January 1^st:

·         Dr Diane Wysowski of the FDA reports an increased risk for cancer of the esophagus with Fosamax use in the New England Journal of Medicine;

·         The Journal of the American Dental Association publishes a study by Parish Sedghizadeh and his colleagues finding an alarming four percent of their dental patients taking Fosamax have osteonecrosis of the jaw;

·         A further NEJM article contradicts everything we have been told about the way bisphosphonates work in the body.  It now seems they increase rather than decrease osteoclast cell production and that these feral bone-absorbing cells are giant and detached. What this means nobody knows. Hardly stuff to inspire confidence in users!

If bisphosphonates offered significant fracture prevention it may be worthwhile debating the benefits and risks. But the majority of the millions of people who take these drugs do not stand to benefit AT ALL.  Meanwhile these are toxic compounds that stay in the body. Their mechanics of action are still not understood, and users remain guinea pigs in a massive experiment.

A diagnosis of osteoporosis on the basis of a bone density test alone is flawed and close to meaningless. The widespread prescribing of bisphosphonates based on a bone density diagnosis has the ‘worried well’ taking the drug in droves believing they are preventing a disease may never have.

The lengthening litany of side-effects: chronic and acute joint bone and muscle pain, sudden serious fractures of the femur, atrial fibrillation, osteonecrosis of the jaw, inflammatory eye disease, and now cancer of the esophagus should have even the most passive of Fosamax , Boniva, Didronel and Actonel users closely questioning their doctors.

A sensation was created in osteoporosis research circles recently (Nov 26 2008) when a report published in Cell revealed that serotonin made by the gut appears to control bone formation. Osteoporosis authorities expressed surprised at the development which the investigators hail as a breakthrough that could lead to a new and very different treatment. The preliminary research was conducted on mice that were engineered to have human genes.

Ninety-five percent of serotonin in the body is produced in the gut and only 5 percent in the brain. The discovery is linked to a gene called LRP5 which controls an enzyme that converts the amino acid tryptophan to serotonin in the gut. The new research indicates that high levels of gut serotonin inhibit bone growth, and lowered levels of serotonin make bone denser.

The serotonin link to bone strength was identified in children with a rare condition of very weak bones and in people with extremely dense jaw bones. These conditions were found to be due to mutations of the gene LRP5 which in turn either impaired or increased bone formation. The projection from the discovery is that a drug may be created that reduces serotonin production in the gut thereby stimulating bone growth.

As exciting as it sounds, the information may not alter what we know about age-related osteoporosis as the investigators found osteoporosis patients tend to have normal serotonin levels. And in the trial, animals with normal genes that were fed a tryptophan deficient diet didn’t grown denser bones. Time will tell whether this apparent ‘breakthrough’ will translate into a safe and effective new treatment.  Read more…

The Osteoporosis Story: Broken Bones or Broken System  examines the historical 1992 redefining of osteoporosis, the multi-billion dollar drug and device industry that burgeoned in the wake of the new definition, and the untold numbers of adverse health events that occurred as a consequence.  The documentary covers the essentials on bone metabolism, details the serious limitations and risks of past and current osteoporosis drug therapies, and questions how ‘evidence-based’ medicine can favour profit before patient safety.  It includes women’s stories on the debilitating effects that bisphosphonate drugs like Fosamax have had on their lives; along with Swedish, Canadian, Georgetown, Harvard  and UCLA physicians’ views on the over-selling of the disease, and comments by leading medical authorities and health activists on the woeful state of much of the science behind the osteoporosis ‘epidemic’ and medicine in general. The Osteoporosis Story was written and directed by Ross Johnston and produced by JPL Productions Dunedin New Zealand.  It can be purchased on line at www.theosteoporosisstory.com

Hard on the heels of the FDA’s January 2008 alert about serious joint bone and muscle pain associated with the bisphosphonates, comes a worrying series of reports of spontaneous fracturing of the femur (thigh bone) in women who have taken Fosamax for several years.

There have long been concerns that the bisphosphonate action of suppressing bone turnover may cause bone to deteriorate in strength and become more brittle over time. It would seem that those fears are being realized and although still small, the number of spontaneous fractures is prompting an FDA investigation of the phenomenon. Reports from Singapore, Hong Kong and the US all have a similar story to tell: the thighbones of women patients on Fosamax for five years or more have simply snapped while they were walking or standing. Some individuals experienced hip and thigh pain leading up to the event, and others had no warning whatsoever. Biopsies after fracture have shown severely depressed bone formation.

Bisphosphonates are becoming easier to take, with once-a-month Boniva (enthusiastically promoted by actress Sally Field), and once-a-year Reclast now available. These are much higher doses than daily and weekly Fosamax and we don’t have evidence from clinical trials to reassure us that the side-effects with these higher doses are not even greater. In her 2005 editorial on the long term safety of bisphosphonates Dr Susan Ott Associate Professor of Medicine at the University of Washington warned: ‘The bisphosphonates in doses used today suppress bone formation to a greater extent than the other antiresorbing medications, so it is possible that microdamage accumulation would develop after 15 or 20 yr—just about the time between menopause and the usual onset of osteoporotic fractures. Certainly this is an issue that requires long-term, carefully designed research.’
Maybe the damage is occurring sooner than she expected. In a July 2008 New York Times article Dr Ott admits to having now seen instances of spontaneous fracture: “I have several similar patients myself. …Prior to these recent articles, there were a few cases here and a few cases there, but they are kind of starting to add up.”
The long term effects of bisphosphonates remain unknown. These drugs accumulate in the body, alter the chemical structure of bone, and have an indefinite half life. This means that the drug’s effect goes on, for better or worse. Stopping the drug doesn’t mean that it leaves the body
Recent evidence for jaw necrosis and other bone necrosis (bone death) associated with bisphosphonate are a further warning that these are drugs with the potential for serious harm.
Vioxx, HRT, Prozac… the list of blockbuster drugs once heralded as safe and effective but later found to put consumers at serious risk goes on. Are bisphosphonates, the multi-billion dollar wonder drugs for bones with over 10 million users worldwide going to end up discredited and discarded also?

We need to fully understand the benefits, side-effects and risks of a drug before embarking on treatment.  Prescription drug information from advertising or brochures employs the clever use of medical concepts that require interpretation. Advertisers rely on our ignorance of such matters and drugs are often made to seem more effective than they really are. Many of us might choose not to take a particular medication if we understood the very small absolute benefit on offer. 

The most common way of presenting the benefit of a drug is to use the observed percentage risk reduction for people taking it. So it is common to hear statements like ‘Aspirin offers men a 32% reduction in risk of heart attack’, or ‘Fosamax offers a 50% reduction in risk for hip fracture’. But these impressive sounding percentages only provide the relative risk reduction and not the more telling absolute risk reduction.

Fosamax ads are a good example. The majority of people don’t fracture their bones. Even ‘high risk’ women and men are at low absolute risk for fracture. In the large trial that measured the fracture benefit of Fosamax, it was found that in a population of 2,027 postmenopausal women with osteoporosis and previous fracture (a high risk group) over a three year period, there were 22 hip fractures in the 1000 women in the placebo group, and 11 hip fractures in the 1000 women who were taking the drug, (a difference of just 11 fractures). Thus 2.2 percent of the placebo group fractured, and 1.1 percent of the Fosamax group fractured. Because 1.1 percent is 50% of 2.2 percent, Fosamax is claimed to reduce hip fractures by 50%. This is a relative risk reduction. The actual or absolute reduction is only 1 percent!

Another and sometimes better way to look at the effectiveness of a drug is to consider the numbers needed to treat or NNT. Numbers needed to treat tend to give a picture of a drug’s effectiveness in terms of the number of people who need to take it in order for one of them to benefit. Aspirin for example, has an NNT of 3.2 when used for migraine headache. That means, approximately three people with migraine symptoms would need to use it in order for one of them to get relief. This is considered an effective treatment. With Fosamax, 90 high risk women would need to be treated for three years in order to prevent one hip fracture in one of them. [i] The remaining 89 would receive no benefit and be exposed to the risks and side-effects of the drug. It is estimated that hundreds of women aged 50 years with low bone density would need to be treated for more than 3 years to prevent one hip fracture in one of them.[ii] 

It is a good idea to ask your doctor what the NNT is for a particular drug and what the absolute risk reduction is.

It is with great sadness that I write of the death on Feb 27 of Barbara Seaman. Barbara was a fearless and prolific writer on women’s issues, probably most famous for challenging the cavalier use of powerful hormones to prevent pregnancy, assist conception, manage menopause, and ‘prevent’ age-related disease. One of the early feminist/activists of the women’s movement in the US, she has been a friend to many and a foe of industry when it has sought profit over safety for women. I had the great privilege of meeting and interviewing her in Manhattan in 2006. She has been incredibly kind to me in the few years that I have known her – connecting me with people in her network, giving me articles for my website and always supporting my work. I will miss her very much. Her friend and co-founder of the National Women’s Health Network Phyllis Chesler has written a moving eulogy and others have added comments. Read also an article from the LA Times on March 2.

The biggest selling drugs of all time – anti-depressants — are only as effective as the placebos they were tested against. An analysis of data from 35 trials including some that had never seen the light of day, has shown that clinically the drugs Prozax, Paxil, Effexor and Serzone don’t work except in a subset of severely depressed patients. The pharmaceutical industry has been accused of withholding data that would have revealed the ineffectiveness of the medication long ago. Whether this shocking news will make a difference to prescribing patterns remains to be seen, but many are calling for the treatment of depression to include safer and effective modalities such as counseling.

Jeremy Laurance, Health Editor Tuesday, 26 February 2008: The Independent

They are among the biggest-selling drugs of all time, the “happiness pills” that supposedly lift the moods of those who suffer depression and are taken by millions of people in the UK every year. But one of the largest studies of modern antidepressant drugs has found that they have no clinically significant effect. In other words, they don’t work. The finding will send shock waves through the medical profession and patients and raises serious questions about the regulation of the multinational pharmaceutical industry, which was accused yesterday of withholding data on the drugs.

It also came as Alan Johnson, the Health Secretary, announced that 3,600 therapists are to be trained during the next three years to provide nationwide access through the GP service to “talking treatments” for depression, instead of drugs, in a £170m scheme. The popularity of the new generation of antidepressants, which include the best known brands Prozac and Seroxat, soared after they were launched in the late 1980s, heavily promoted by drug companies as safer and leading to fewer side-effects than the older tricyclic antidepressants. The publication in 1994 of Listening to Prozac by Peter Kramer, in which he suggested anyone with too little “joy juice” might give themselves a dose of the “mood brightener” Prozac , lifted sales into the stratosphere. In the UK, an estimated 3.5 million people take the drugs, collectively known as selective serotonin reuptake inhibitors (SSRIs), in any one year and 29 million prescriptions were issued in 2004. Prozac, the best known of the SSRIs made by Eli Lilly, was the world’s fastest-selling drug until it was overtaken by Viagra. In the study, researchers conducted a meta-analysis of all 47 clinical trials, published and unpublished, submitted to the Food and Drug Administration in the US, made in support of licensing applications for six of the best known antidepressant drugs, including Prozac, Seroxat – which is made by GlaxoSmithKline – and Efexor made by Wyeth. The results showed the drugs were effective only in a very small group of the most extremely depressed. Two drugs were excluded from the study because of incomplete data. A third drug, chemical name nafazodone, has been withdrawn from the market because of side-effects. Professor Irving Kirsch of the University of Hull, who led the study published in the online journal Public Library of Science (PLoS) Medicine , said the data submitted to the FDA would also have been submitted to the licensing authorities in Britain and Europe. It showed the drugs produced a “very small” improvement compared with placebo of two points on the 51-point Hamilton depression scale. That was sufficient to grant the drugs a licence but did not meet the minimum three-point difference required by the National Institute for Clinical Excellence (Nice) to establish “clinical” significance. Yet Nice approved the drugs for use on the NHS in the UK because it only had access to the published trials, which showed a larger effect. Professor Kirsch said: “Given these results, there seems to be little reason to prescribe antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide a benefit. This study raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported.” Five years ago, there were allegations that antidepressant drugs were addictive and could trigger suicides. All but Prozac were banned for children, although a major investigation on the safety of medicines cleared them of causing suicide in adults. Alternative treatments for depression, such as counselling or physical exercise , should be tried first, Professor Kirsch said. The pharmaceutical companies had withheld data that was available to the licensing authorities so that doctors and patients did not understand the true efficacy, or lack of it, of the drugs. “This has been the frustration. It has made it very difficult to answer the question of whether the drugs work. The pharmaceutical companies should be obliged when they get a drug licensed to make all the data available to the public. When you analyse all the trials of these SSRIs, both published and unpublished, it leads you to more sober conclusions,” he said. Tim Kendall, deputy director of the Royal College of Psychiatrists’ research unit, said the findings, if proved true, would not be surprising. As head of the National Collaborating Centre for Nice guidelines on mental health, he said it had proved impossible to get access to unpublished trials in the past. “The companies have this data but they will not release it. When we were drawing up the guidelines on prescribing antidepressants to children [in 2004] we wrote to all the companies asking for it but they said no. The Government pledged in its manifesto to compel the drug companies to give access to their data but that commitment has not been met.” The new finding would make doctors “much more cautious about prescribing the drugs,” Mr Kendall added. GlaxoSmithKline, makers of Seroxat, said the authors of the study had “failed to acknowledge” the very positive benefits of SSRIs and their conclusions were “at odds with the very positive benefits seen in actual clinical practice.” A spokesperson added: “This one study should not be used to cause unnecessary alarm for patients. Lilly said in a statement: “Extensive scientific and medical experience has demonstrated that fluoxetine [Prozac] is an effective antidepressant. Wyeth said: “We recognise the need for both pharmacological and non-pharmacological treatments for depression.” On the new training for therapists, Mr Johnson said the programme signalled a decisive shift away from drugs in favour of non-drug treatments for depression. “We are not taking the decision away from clinicians,” he said. “For many, medication is successful. But talking therapies can have dramatic effects. We have put a lot of emphasis on medication in the past and it is about time we redressed the balance and put more emphasis on talking treatments.” The treatments that do work * Exercise: Helps some people with depression. Douglas Adams, author of The Hitchhiker’s Guide to the Galaxy, said running helped him cope with depression. * Friends: Talking through your feelings can help in mild depression with a friend or relative or in a self-help group. * Cognitive behavioural therapy: Teaches you to challenge negative thoughts and feelings of hopelessness. * Interpersonal therapy: Focuses on relationships and problems such as difficulties with communication. * Counselling: Helps you think about the problems in your life and find new ways of dealing with them. * Antidepressants: Increasingly seen as a second-line treatment, if exercise or talking treatments do not work.