Vioxx and the TGA

[sydunisportsmed]

Great episode of 4 Corners on the ABC last night regarding the Vioxx fiasco. This is a fiasco when you see the story as outlined by the program. The jaw dropper for me is that the TGA (in Aus) and the FDA (in USA) receive all of their funding directly from the drug companies, rather than the government, which means that they don't want to ever bite the hand that feeds too hard.

The facts on Vioxx:

2000 NEJM publishes the VIGOR study, showing a 5 fold increase in cardiac events of Vioxx over Naprosyn (along with decrease in gastro events).
2004 a placebo controlled study is finally completed by Merck, showing a 3 fold increase in cardiac events of Vioxx over placebo, prompting the withdrawal of the drug.

The Merck and vast majority of the expert medical community response to the VIGOR study was that: "Naprosyn probably decreases cardiovascular events, so the increase with Vioxx is probably spurious". It was a reasonable hypothesis, but it was obviously only a HYPOTHESIS and has since been proven to be wrong.

Why did the medical community, and drug regulators, get sold on a hypothesis between 2000 and 2004, paying no attention whatsoever to option B (which turned out to be correct), that Vioxx increased the risk of heart attack?

The answer to this question is obviously that the reach of the drug companies in terms of sponsorship is so wide that criticism is muted.

Much as I am not a fan of the tort law system, the plaintiff lawyers would be rubbing their hands to get at this one, because the regulatory bodies have not shown the conservatism that they should, and the general public has been used as guinea pigs between 2000-2004, when cardiovascular warnings and exclusions should have been far more prominent.

If you didn't see 4 Corners, get a tape or watch for the replay.

[sydunisportsmed]

NB it came out that the Aussie TGA has been far more conservative than the US FDA, although still not enough. Vioxx was never recommended to be taken at > 25mg / day in Australia, which has meant that the number of heart attacks and strokes 'caused' by the drug was a lot less than in the USA, where many people were on 50mg / day. Also Vioxx was held back from release in Australia a bit longer than in the USA, so that Celebrex (which is less COX-2 specific and hence safer from a cardiovascular viewpoint, although not GI) had greater market share in Australia than in the US.

The FDA being Cowboys is not surprising, as they allow oral anabolic steroids to be over the counter in the USA, which must have something to do with the number of gun deaths, as aggressive young males self-medicate to pump their testesterone levels up even further through the roof. George W and your Cowboy predecessors, take a bow.

[injuryupdate]

Interesting articles from the BMJ:

http://bmj.bmjjournals.com/cgi/content/full/330/7496/855

http://bmj.bmjjournals.com/cgi/content/full/330/7496/911

The last one is about a good film that might be worth seeing when it comes out.

[hhh]

Just out of interest what kind of perks have you received from drug companies over the course of your career? Perhaps for ethical reasons you should give away the golf clubs, dinners, brief cases of cash, holidays, dates with hot models etc given to you by the Cox-2 companies as prizes on this website?


Interesting articles from the BMJ:

http://bmj.bmjjournals.com/cgi/content/full/330/7496/855

http://bmj.bmjjournals.com/cgi/content/full/330/7496/911

The last one is about a good film that might be worth seeing when it comes out.

[injuryupdate]

Drug companies are in the business of making money for selling their product, so you don't expect them to necessarily be ethical.

Where the process is breaking down is apparently that:

(1) The regulatory bodies, which are meant to be keeping the drug companies in check, are getting paid by the companies themselves, so they are not doing a lot of kick-arse regulating. Mind you, the surgeons regulate whether surgery is being done ethically, and this is a similar problem.
(2) Not sure whether it happens in Australia, but these BMJ articles suggest that drug companies can buy prescribing information of doctors. This is a critical step, because it suggests that the companies can lay on greater 'incentives' to loyal prescribers (i.e. kickbacks). The equivalent would be in politics if the parties could work out who you voted for, in terms of how much they would represent you. Prescribing should be secret ballot, so you have the right to listen to a rep try to convince you to use their drug, but you don't feel pressure when you are writing an actual prescription.

[hhh]

so what kick backs have you scored?

[sydunisportsmed]

so what kick backs have you scored?

I know this is hard to believe, but in sports medicine we hardly write any prescriptions compared to other docs, so the drug companies are only vaguely interested in us.

The real potential for kickbacks in sports med is from surgeons and radiologists, where we have high rates of referrals.

[hhh]

Cyclo-Oxygenase-2 Inhibitors: Beneficial or Detrimental for Athletes with Acute Musculoskeletal Injuries?

Author: Warden, Stuart J.1
Source: Sports Medicine, 2005, vol. 35, no. 4, pp. 271-283(13)

Abstract:
The major goal of clinicians when treating acute musculoskeletal injuries is to return athletes to their pre-injury level of function, ideally in the shortest time possible and without compromising tissue-level healing. In this regard, a commonly used intervention is the taking of NSAIDs. These are used to limit the amount and duration of inflammation, and to control pain. While NSAIDs have become synonymous with the management of acute musculoskeletal injuries, their efficacy has yet to be proven. This is of particular concern in view of recent research investigating the latest class of NSAIDs – selective cyclo-oxygenase-2 inhibitors (COXIBs). COXIBs were developed to reduce the adverse gastrointestinal (GI) effects of traditional NSAIDs. While they have beneficial anti-inflammatory and analgesic properties, and appear to facilitate earlier return to function following acute injury, the effect of COXIBs on tissue-level healing is currently unknown. In experimental animal models of acute injury, COXIBs have been shown to be detrimental to tissue-level repair. Specifically, they have been shown to impair mechanical strength return following acute injury to bone, ligament and tendon. Clinically, this may have implications for ongoing morbidity and future injury susceptibility. However, the current animal studies have limited translation to the clinical setting, particularly because of significant limitations relating to drug use and dosage in these studies.

There is currently no randomised, controlled trial evidence of the tissue-level effects of COXIBs on acute musculoskeletal injuries. In addition to questions relating to the effect of COXIBs on tissue-level healing, further questions regarding the use of these agents have been raised given a recent link being shown between one COXIB (rofecoxib) and an increased risk for adverse cardiovascular events. Whether this finding is related to the individual properties of rofecoxib or is a class phenomenon is the subject of ongoing investigation. However, in light of the potential risks associated with using COXIBs, an acceptable and possibly safer alternative in the management of acute musculoskeletal injuries may be to use traditional NSAIDs. Traditional NSAIDs do carry the potential for greater adverse GI effects and their clinical effects on tissue-level healing remain relatively unknown. However, they do not appear to be associated with adverse cardiovascular effects, and they are effective pain relievers and cheaper alternatives.

[Snuffy]

Yeah but you'd be propping up the cortisone companies enough to keep them in business