Is promotion of "excessive sleepiness" the latest example of disease mongering

I previously posted about the notion of "disease mongering" . Ads are recently appearing alerting the public and/or the medical profession to the "common and debilitating" of excessive sleepiness (ES). The Epworth Sleepiness scale is recommended to determine if your level of sleepiness rises to the level of being designated as "excessive".The reader is told that 50 % of work related accidents and 25% of household accidentss are due to ES,it is common in depression (as many as 1 our of 5), 80% of Parkinson pateints have it and, of course, it is common in patients with obstructive sleep apnea (no argument there). I also posted about a new alertness drug,modafinil, which was featured in an NEJM article and was accompanied by a somewhat skeptical editorial.In Jan. 2002 the FDA sent Cephalon (modafinil's manufactuer) a warning letter for "false and misleading material" which promoted its use for sleepiness and lack of energy when at the time it was only approved for narcolepsy. In October 2003,the FDA expanded the approved use to obstructive sleep apnea/ hypopnea related sleepiness and to sleepiness due to shift work sleep disorder.Interestingly, even though the Cephalon ES advertisement mentions Parkinsons disease as a condition in which excessive sleepiness may be a issue, a recent RCT from Baylor Medical School failed to show any benefit from modafinil in Parkinson patients.In 2005 a number of RCTs were published that evaluated modafinil in:ADHD,Obstructive Sleep Apnea,shift work shift disorder,cocaine dependence,shizophrenia,patients with incomplete response to SSRIs and as an analgesic potentiator. There were with mixed results. It may well prove to be of some value in several conditions but my concern is with the advertisement approach in which physicians are encouraged to "screen" for ES as it is "often unreconized and untreated".Physicians are encouraged to include the Epworth Sleepiness Scale into "routine evaluations".I wonder if we be seeing that ES seminars will be part of the medical meeting scene and "thought leaders" will be discussing the latest research involving modafinil in a variety of conditions and patient advocacy groups will enlisted and can direct to consumer advertizing be far behind. In short the whole disease awareness campaign to promote a condition as serious,common,underdiagnosed and treatable might be gearing up.Interestingly,today (12/3o/04) I received in the mail an invitation for a seminar worth 4 hrs. of CME on the topic of excesssive sleepiness.I'm going to pass on this one.

More on community acquired pneumonia and guidelines

The Dec. 20, 2005 issue of the Annals of Internal medicine published an article evaluating various implementation strategies for pneumonia guideline implementation.This was a RCT but not a trial to see how effective or safe the Pneumonia Severity Index (PSI) is but to determine the preferred method to implement the guidelines based on the PSI. It did not go unnoticed that one of the authors is Dr. MJ Fine who is credited with the Fine PSI.The authors concluded that a "high intensity" intervention increased the proportion of "low-risk"patients with pneumonia who were treated as outpatients. A key outcome of interest was the number treated as a outpatient.Importantly they listed numerous contraindications to outpatient treatment.These conditions trumped the PSI.Many of the reasons that inpatient treatment was opted for were the reasons that clinicians used to hospitalize patients in the study quoted in a earlier posting.The trump list included:frailty,serious comorbid conditions,extreme abnormalities in vital signs or laboratory values,clinical or psychosocial factors that could compromise the outpatient use of oral antibiotics.Viewed in this light,the PSI is a much more limited tool.It is useful unless any of the above list applies.Most of the items in the list require clinical judgment.How frail is the patient,how seriously abnormal the lab finding, etc.etc.The authors tout the value of the PSI and for them apparently the only issue is how best to implement it.However, the PSI is only a part of the assessment process as they implicitly admit by recognizing the many clinical factors that override its use. I find the importance placed on proportion of patients treated as outpatients somewhat disturbing.
While we do not want to needlessly hospitalize patients the basic doctoring mission is to do the right thing for patients and in that regard to measure success at what we do in terms of how many patients did we send home with pneumonia seem to miss the main point of what physicians do.The AJM article previously blogged about pointed out the importance of clinical judgment, the Annals article seemed narrowly confined to how to minimize hospitalizations by determining the best method of implementing the PSI and seems to ignore the importance of clinical judgment .Dr. Robert E. Siegel from the Mount Sinai School of Medicine in an editorial in the American Journal of Medicine (Amer. J. Med. 118:1311,dec.2005) said of the PSI ,"formulas, points and classes, no matter how helpful are no substitute for experience and judgment."A similar view was expressed by the American Thoracic Society in their 2001 paper on CAP when they spoke of the admission decision as an "art of medicine" decision and said that no rule by itself can determine the need for hospitalization.

Community acquired pneumonia-Pneumonia severity index falls short

One of the operational rules of the medical-quality "thought leaders" is that "variation is bad" and it must be mitigated.(The borg has a similar philosophy and more effective implementation methods).According to an interesting and useful article by Marrie and Huang (American Journal of Medicine:118:1357,2005)marked variation in the admission rate for community acquired pneumonia(CAP) lead to the development by Fine et al of the pneumonia severity of illness(PSI) score as a guide to the admission decision. These AJM authors reviewed 3065 admissions in Edmonton with a diagnosis of CAP over a 2 year period. 586 (19.1%) were classified as "low risk" using the PSI. Was the hospitalization of " low risk" patients a shameless, thoughtless waste of precious medical resources? Apparently not. Almost half ( 48.4%) were sick enough to be in the hospital for more than five days.19% suffered one or more complications and 31% were still unable to ear or drink to maintain hydration by the fifth hospital day. Clearly the admitting physician's clinical judgment appropriately overruled the PSI score. Fine's classification system keys to mortality rate.Those in risk classes I to III have a < 1 % mortality rate.The authors point out that the PSI does not work if the patient has COPD or pulmonary fibrosis or HIV infection or immuno suppression, etc. etc. and there are important prognostic factors not captured by the Fine index including nausea,shortness of breath and diarrhea . Their final sentence is: " It is clear that low-risk patients are a heterogenous group and that a low risk for mortality is not the only factor to be considered in admission decisions".Fortunately for a significant number of patients with CAP, the admitting physicians used what seems to often elude guidelines and algorithms namely clinical judgement.Of course,low risk patients are heterogenous:patients are heterogenous-biological variability is what it is all about. All patients classified as having the same illness are not the same,patients do not all react to the same treatment in the same way.Our ability to figure everything out ahead of the facts as they unfold is very limited.Humans dealing with the human condition are doomed to have to improvise and be inventive and use judgement.Off-the-shelf rules do not and never will adequately cover all the contingencies that we face in medicine or for that matter in most everything else. Credit is due to the authors of the Emonton pneumonia critical pathway which seemed to have emphasized that "physician judgement should take precedence over guidelines" an insight seemingly unable to penetrate into the bean counter mentality.

Have patient monitor own blood pressure-What a thought.

Medscape has a good summary on the current Blood pressure measurement advice. Home mesurements are important and may be a better indicator of the "real" day to day pressure than the occasional office reading.I have told patients that for years and asked them to buy an automatic cuff and to bring in their cuff and check it against the doctor's office mercury BP unit. Dr. George Burch, chief of Medicine at Tulane when I trained, told his patients that and in those days had a family member learn how to take the BP with the arm cuff and stethoscope (automatic units had not yet been invented). Burch also emphasized the importance of proper cuff size. It looks like it took 40 years for the American Heart Association to catch up with my old prof's advice.

Long acting beta-agonist (LABAs) and the dilemma of "coarse grain" data

The FDA has recently issued an advisory saying that LABAs may increase the chance of severe asthma episodes and death when those episodes occur,this warning appearing more than 10 years after salmeterol was first approved for use in the U.S. Formoterol ,another LABA is used less widely in this country but the combination of salmeterol and a steroid sold as Advair is very widely used by allergists, pulmonologists and family practice doctors.The warning does not apply to LABA use in COPD.
As early as 1994 some increase in asthma deaths was attributed to salmeterol. A Lancet article
by Castle et. al which was designed to compare albuterol with salmeterol showed a non significant increase in death by a factor of 3 in the salmeterol group while asthma control seemed better in those treated with salmeterol. Even though the increased number of deaths was not statistically significant, the FDA's concern lead GSK to initiate the SMART trial, the interim analysis of which has lead to further concern and the warning issued by the FDA. In this trial salmeterol was compared to placebo and after 26,000 patients were enrolled, data indicated that asthma related deaths were 4.4 times higher in the treatment group. The reason that I call the data coarse grained is that neither the Lancet paper or SMART have adequate data regarding which patients were also receiving inhaled steroids (ICS) to make a determination regarding whether steroids will mitigate or eliminate any increased risk from salmeterol.This is important as standard therapy consists of adding an ICS for asthma as severe as"mild persistent", so we need to know the risk of adding a LABA to ICS for the more severe degrees of asthma. Two large RCTs do not provide that critical information because there is not enough detail and/or statistical power available to indicate if there were increased deaths occurring in patients receiving ICS plus LABA.A post hoc analysis suggested that the risk was greater in African-Americans.
It has been the experience of pulmonary docs and allergists that for most patients the addition of a LABA to ICS is beneficial yet there may well be the possibility of a rare serious side effect.
LABAs , to a greater degree than short acting beta agonists have been accused of down regulating the beta 2 adrenoreceptor and inducing subtherapeutic response to the rescue inhalers which is a proposed mechanism for the worsening of asthma. It may well be that genetic polymorphism in these receptors may account for a small subset of patients who are at risk of worsening asthma if treated with LABAs.The coarse grain data we currently obtain from epidemiologic methods cannot tell us who they are. Should we change our practice in light of the FDA warning? I continue to believe LABAs are appropriate to add on to the asthma patient's regimen when ICS and rescue inhalers are not enough. Theophylline preparations and leukotriene antagonists may be used instead but the ease of use,the low incidence of acute side effects and the patient acceptance of the LABAs make me think there will be little change in the number of prescriptions written. This belief is strengthened by the MEDSCAPE review of the Harvard study suggesting that many physicians do not pay that much attention to the black Box warnings anyway. The National Jewish website has this page that should reassure their asthma patients and at least gives the impression that they plan no major changes in their treatment approach.This page from the CMA journal give a good overview and some common sense recommendations with which most would agree.These include:LABAs are not to be used as rescue inhalers,be sure the patient is taking an ICS before LABAs are added to the treatment plan, and use the lowest dose when possible and if symptoms worsen contact your physician.

DCCT/EDIC : Glycemic control may decrease cardiovascular risk

For a number of years I have told type 2 diabetics that it is important to control the blood sugar to decrease the risk of damage to the eye, kidneys and nerves but that we needed a different approach to decrease their risk of heart disease. Now the follow up part of the landmark DCCT give us evidence that at least in type 1 diabetics that glycemic control decreases the risk of cardiovascular disease. The decrease in cv disease risk is impressive,in part, because the treatment group enjoyed lowered blood sugar values for only 6.5 years. After that, during the followup period (from 1993 until Feb. 2005) there was little difference in glycemic control.Yet apparently that 6.5 years of better control translated into an impressive 57 % decrease in non fatal MI,stroke and cv disease death. We do not know if this benefit will accrue to type2 diabetics when and if they achieve control such as that seen in the treatment group of the DCCT (glycosylated hemoglobin of 7.4 versus 9.1 in the usual treatment group) but my bet is that it would. You have to wonder what results would have been seen if the Hb A1c values were closer to current treatment goals. I like to poke fun at the RCT religious zealots but a well designed and executed RCT-such as the DCCT- is a thing of beauty.

Evidence Based Medicine proponents need to watch out for their friends

Dr. H. Brody et al authored an interesting article in a recent issue of Perspective in Biology and Medicine which point out problems posed by so-called friends of EBM. They speak of those who
exhibit "decerebrate genuflection before the alter of the RCT".These are the folks I spoke of in a earlier blog who denigrate the use of parachutes because their use has not been validated by a RCT.The second group of friends are the commercial sponsors of RCTs who sometimes at least corrupt the process by stacking the deck to mislead the readers.The third group is populated by those "advocates" such as HMOs and insurance companies who also corrupt the process by using RCT's to justify limiting care aka saving money whose mantra seems to be " If there is no RCT we don't need to pay". Much of the Autumn 2005 issue of Perspectives is devoted to thoughtful essays on EBM. Unfortunately there is no open web resource for the entire issue which made me actually go to the Medical society library to read it, a trip I have not made in years. One more quote, this time from the article from Dr. R. Upshur who speaks of a "near religious belief [in which] assertion has replaced argument."

The efficacy of parachutes and the nature of evidence based medicine

Dr.RW in his increasing prolific and useful blog recently referenced an article by Dr. Norman Laton, a professor of neurology at Cornell.Laton points out that RCTs are not always needed nor always possible. There is a long list of things doctors do that do not have RCTs supporting their use. A few are: appendectomy for acute appendicitis,inserting a chest tube for tension pneuomothorax,setting a fractured bone,draining an subdural hematoma,taking time to listen to a patient,doing a lumbar puncture with suspected meningitis,getting an ekg on a patient with chest pain. Dr. Laton particularly criticizes EBGs (evidence based guidelines) that consider only RCTs as evidence.
The current EBM gurus as well as those who are credited with the foundational thinking of EBM do not maintain that RCTs and meta-analyses are the only evidence that we can use in determining the value of what we do.They realize that clinical judgment and patient values cannot and should not be cast aside.However,I hear physicians at meetings as well as medical student's comments that indicate they seem to believe that if there is not a RCT to a specific point then the tenets of EBM dictate that that procedure,treatment or whatever cannot be rationally used and to use it anyway will not only waste precious resources but may well be harmful. Here's the thing;There are many things that we do that are correct and which no RCT addresses. Further there are RCTs that are facile and basically empty (such one that compares a new antibiotic or ARB , or ACE or PPI with a barely adequate or inadequate dose of a comparator drug.There are many of these studies that drug companies do to show comparative efficacy with a drug which has proven efficacy).
A similar thought to some of what Dr. Laton said was expressed at a recent CME on hypertension by Dr. Tom Giles, President of the American Society of Hypertension when an audience member questioned some statement Giles made because there was " no evidence based medicine" proving the value of the proposed medical management issue.Paraphrasing Giles's reply.'RCTs can be very useful although some provide little useful new information.And some things may not need a RCT for validation. It would be hard to recruit subjects for a RCT to investigate the efficacy of parachutes to manage gravitational challenge.'

Endurance exercise hyponatremia-how does it happen?

One of the gurus of the medical aspects of endurance exercise, Dr. T.D. Noakes, of Cape Town has published a detailed study of 2,135 endurance event participants and gives us slow-marathon and slow- ultramarathon runners some authoritative insight ( Only an abstract seems available so far)into marathoner's hyponatremia. First of all some folks simply drink too much water.These people actually gain weight during an ultra event.Most runners loose weight, which, it turns out, is safer.The second reason is "inadequate suppression of ADH". The third reason he offers is failure to mobilize osmotically inactive sodium from bone. Looking at his data, 19% of the 2,135 runners were hyponatremic in the range of a sodium from 129-135 and another 11% had values less than 129. Weight gain during the race was the tip-off to low serum sodium values but most of those gaining weight (70%) did not have low sodium values. In a separate,earlier publication, Noakes et al studied 6 Iron man participants with a history of hyponatremia and 6 control Iron Men with a water loading experiment and was unable to discern any characteristic pathophysiological features to explain why some do and other do not develop low serum values. Hyponatremia can occur in some elite runners although data from several marathons indicate that the current apparent increase in marathon hyponatremia more typically occurs in slower runners who tend to overhydrate,are inexperienced and tend to be thin and female. The older advice to drink at each hydration station and do not wait for thirst has changed and some race directors are actually recommending fewer aid stations.The official hand book of the New York marathon recommends only 8 oz. every 20 minutes as a maximum. Mild hyponatremia, according Noakes' chapter in "Endurance in Sport" by Shepard and Astrand, is usually mild and self limiting but there are dramatic exceptions including fatal cases.
Hopefully,as inexperienced marathoners are disabused of the notion of excessive water intake during a marathon we will be seeing fewer cases.

charges, counter charges,innuendos and more re: Vioxx,NEJM,Merck,Cleveland Clinic

Almost everyone involved in the Vioxx matter is either accusing someone of something and/or is being accused of something.The editors of NEJM are accusing Merck of not being forthcoming with the VIGOR study heart attack data.Merck counters with the statement that they did not supply NEJM with the "extra" heart attacks because they occurred after the cutoff date for data accumulation and that they did report the deaths to the FDA. Eric Topol is outspoken in his criticism of both Merck and the FDA. Topol has been accused of conflict of interest because he was advisor to a hedge fund which is said to have sold Merck short. Topol has been relieved of his position at the Cleveland Clinic Lerman school of Medicine where he had been provost and chief academic officer. Topol has charged that this action resulted from his role in criticism of Merck both in and out the court proceedings. The clinic counters that the job loss was the result of administrative reorganization and was not related to Topol's role in the Vioxx matter.The CEO of the clinic, Dr. Toby Cosgrove, who demoted Topol had been accused of conflict of interest in several other matters as outlined in interesting detail by hcrenewal .Some medical bloggers question the motives and the significance of the NEJM editors publishing their e-editorial describing the missing 3 heart attacks while the third Vioxx trial was still underway in federal court in Houston.
And if all of that is not enough, McDonalds has accused both Topol and Cosgrove of opportunism and demogogery in working to remove McDonalds from the Cleveland Clinic.This,of course is note related to the Vioxx and the Topol demotion issue, but makes me think how easy it is to make accusations and how hard and often expensive it is to prove them. What is even harder is to try and sort it all out from newpaper stories and boggers comments and revelations. My bias and my sympathy lies with Dr.Topol and not with Merck . As to Topol v.Cleveland Clinic administration, I do not know how to begin to sort all of that out. It could be as simple as a power struggle between two very accomplished physicians or one act in a morality play in which big interests and big conflicts of interests are on the stage.

NEJM editors claim Merck withheld data re: Vioxx study heart attacks

In a turn of events more typical of John Grisham novel than a real trial in a federal court, editors of the NEJM announced in their online journal they had become aware of Merck withholding data from the Vigor trial manuscript which would have made the cardiovascular relative risk even higher.This occurred while the third Vioxx trial is underway in federal court in Houston.Just when you thought revelations about Merck's alleged misdeeds could not get any worse, the editors at NEJM accuse Merck of deleting data so that three additional heart attack deaths did not appear in the data tables.This change did not alter the basic finding of increased risk in the Vioxx treated patients so you wonder why the researchers bothered to make that change.Material,that included internal Merck e-mails- that become public during the trial seemingly lead the editors to take the unusual action of re-assessing data from a several year old article. This raises the lack of credibility to previously unreached levels as regards clinical trials funded by drug companies. Merck has issued a statement in reply to the NEJM editorial statement that in part states the three deaths occurred after the agreed upon cut-off date for the end of the trial and those deaths were reported to the FDA. We have not heard the last of this. We teach medical students that the reasons for an association or lack of one in a clinical study are: chance, causality,bias and confounding. The fifth factor, fraud, was not typically emphasized in that regard, now it maybe it should be.

More problems with CPOE-this time apparently fatal ones

Dr. Andy comments on a tragic situation at a pediatric ICU resulting from the institution of a computerized physician order entry system(CPOE) that apparently significantly impeded proper care with resultant increase in ICU mortality. This experience is described in an article in Pediatrics.(abstract only for non-subscribers)
Previously I had commented on increased adverse reaction rate reported from a VA hospital after they put CPOE into place, but this is worse. According to the proposed explanations of what went wrong, basically the CPOE disrupted the normal flow of care by skilled nurses and doctors and seriously interfered with the procedures,practices,systems and mechanisms that were designed or evolved in that pediatric unit and while they may have not been perfect they were obviously much better than what replaced them.Treatments and diagnostic tests were apparently delayed and the important team work between bedside nurses and physicians was seriously damaged.The ICU is not a forgiving place for delays in treatment and poor communication.I hope this important and frightening article is widely read and appreciated. Systems that alter critical operations at a hospital should not be implemented without considerable input and advice from the people on the ground (the docs and nurses) and need a shakedown cruise or two before it goes live and should run parallel with the old way until folks can determine if it works.If a given IT "solution" will be useful or harmful is an empirical question and to assume that safety or efficiency or whatever positive thing is claimed will automatically occur just because it is IT is foolish. A recent JAMA article on error rate with a CPOE attracted considerable interest.The following quote from an article commenting on that study gives a good description of what it is that computer systems have to deal with in the medical management of patients."Designers of healthcare information technology must be exquisitely sensitive to the non-linear,context dependent, fast communication- dependent,interruption-filled,uncertain and collaborative nature of hospital clinical practice". Unforeseen circumstances will occur with new systems and ways of doing things.We should not be surprised at that.However, in this era of evidence based medicine it is ironic that physicians permit systems to be implanted without evidence of efficacy or safety of a particular system in a particular setting.

The medical profession-have we been divided and conquered?

Thoughts plucked for the insightful editorial ( for which I do not seem able to set up a hyper-link) by Dr. Philip R. Alper (Internal Medical World Report, November 2005) makes me think we have been divided by the power of managed care and the self-interested economic activities of hospitals.Somewhere in the mixture the hospitalist movement may also serve to divide and conquer even if that may be an unintended consequence.
The disruption of the traditional and customary lines of referral occurred early in the managed care era. It became too routine to refer to physicians not because you thought they were the best for your patient but because they were on the patient's insurance plan.Dr. Alper speaks of the growing divide between physician who practice at hospitals and those who are just on the staff. As hospitalists and intensivists grow in number so do the IM and FP docs who do not even go to hospitals except often enough at staff meetings to maintain privileges. He discusses growing tension between those specialists, such as orthopedists, who must be on call at the ER and the docs who-after hours and often during hours-send their patients to the ER and never see them there or later in the hospital.He talks about hospitals who advertise the purported advantages of certain operative procedures by some of its staff surgeons while other surgeons on staff who do not do that particular procedure fume.His theme was in part that all of this and more have lead to a major decrement in the collegiality of physicians. He believes one manifestation of this is the loss of previously almost universal practice of giving professional courtesy. Previously Dr. Alper has written that HCFA and insurance companies have poisoned the relationship between physicians and patients, now he posits that those and other forces seem to be poisoning the relationship between physicians.

Might some good come from the drug-trial book cooking of big pharma?

What good could possibly be derived from publishing misleading medical information in main line journals?
I'll admit this may be carrying the half-full half-empty glass thing a bit too far. But here goes. We-the medical professionals-are now on notice that when we read about a RCT or doze through a meta-analysis that we have to be much more critical and skeptical that ever before. We should now more than ever know better than to say that because there was a RCT showing that drug x did whatever good thing that we now should use that drug and now we have evidence based medicine behind our decision. An RCT may be the best tool we have to assess drug and procedure efficacy and give some data regarding safety but one or even two RCTs are not necessarily sufficient to wrap the banner of EBM about the decision to use that medication.RCT design can be structured to give positive results that are in fact bogus. For example,you can compare your new drug with a lower than maximally effective dose of a old drug and there are many other more subtle tricks of the trade that we can now detect thanks to the growing recognition of the sometimes duplicitous behavior of drug companies. Big Pharma's antics have made us better consumers of medical information and more able to recognize the various forms that pharmaceutical infomercials (I 'm taking about free dinner talks and some of the material in the throwaways) now take. Importantly, medical journal editors are taking steps to make more transparent the mechanics of how clinical trials are put together and analyzed and requiring the authors to make more meaningful statements regarding their role in the publication.Academic centers are beginning to access FDA data and independently re-analyze date regarding drug safety and efficacy.(Kudos to the folks at Cleveland Clinic for leading the way in that regard).Lastly, although hyper-rapacious and overreaching plaintiff attorneys have earned their less than overwhelmingly positive reputations with physicians and the general public, the VIOXX trials may well not only inform us about how drug companies may place short term profits above all else but will serve as a major wake up call to the drug industry that that the jig is up in regard to misleading the medical profession and the public about their products.
We have learned that RCTs are vulnerable to manipulation and- because of that and the fact that typically the subjects chosen for the trials are not always enough like the patients we treat-as important a tool as they can be, they need to be classified as more as a silver standard than a gold standard. Knowing that a given finding resulted from a RCT should not end the discussion, that fact should be the beginning of a consideration of the details of the trial and analysis wherein sometimes the devils lie.Our recognition of some of the ways Big Pharma has manipulated certain aspects of evidence based medicine may have served to alert and inform us about the limitations of EBM.

Noted Cleveland Clinic Cardiologist blasts Merck in deposition

Eric Topol,chief of cardiology at Cleveland Clinic has little good to say in his deposition about Merck's actions in the Vioxx matter and in the efforts of Merck's executives to silence his criticism.Importantly, for the current trial,Topol's deposition stated that Vioxx could increase risk of heart attacks soon after starting the drug.How soon any increased cv risk might manifest itself is apparently an issue at the trial. Merck is taking the position that Vioxx increases risk only after 18 months of use; the plaintiff in this case used it for only one month. This is the third Vioxx trial. His deposition criticized Merck's alleged efforts to spin trial data to decrease any statistical demonstration of increased risk and what he described as the company's efforts by their executives to influence him to stop his publications regarding Vioxx and CV deaths. He states that a former CEO of Merck contacted the CEO of Cleveland Clinic and a VP visited Topol to attempt to dissuade him from publishing anything reflecting poorly on their drug.
All of this came to light on the heels of Topol et al's JAMA publication regarding CV risk of a dual PPAR agonist, muraglitazar, which Merck had submitted to FDA for approval. Merck's interpretation of their data showed no increased risk while Topol and colleagues did.
The David and Goliath drama playing out between Topol and one of the biggest of Big Pharma is just one aspect of the still growing lack of credibility of drug company clinical trial data by the medical community and the general public.Another David story is told by HCRENEWAL wherein a Sheffield University researcher, Dr. Aubrey Blumsohn, is suspended by the university because of a dispute between Proctor and Gamble and Blumsohn regarding a study involving risedronate. That case seems to exemplify the "golden rule" which states that whoever has the gold make the rules.