There are many problems with science. Science will never be perfect, but only people who do not understand science claim that it should be perfect.
One of the problems with science is publication bias. A paper that has a positive results about a brand name drug is twice as likely to be published than a paper with neutral results or with negative results.
The drug company has no incentive to publish a paper that does not make their drug look good. If you think that this is conspiracy talk, ask the drug companies for the results of the studies that have not been published.
Dr. Joe Lex states that we should take the published positive results for any drug and cut the claimed benefit in half, because the first published studies are often the most positive results that we will ever see.
Positive results may be seen as the best case scenario.
Look at the way that the antiarrhythmic amiodarone (Cordarone by Wyeth Pharmaceuticals Company, a subsidiary of Pfizer Inc.) became the ACLS (Advanced Cardiac Life Support) standard of care for VF/Pulseless VT (Ventricular Fibrillation/Pulseless Ventricular Tachycardia). One study showed that we had more ROSC (Return Of Spontaneous Circulation) with amiodarone than with lidocaine (Xylocaine by Astra Apotekarnes Kem Fab [SE], now AstraZeneca LP, originally patented in 1948 as a local anesthetic, but probably no longer patent protected as an antiarrhythmic at the time of the studies).
In the 2000 ACLS guidelines, we were told that we should treat every VF/Pulseless VT patient with amiodarone.
A single study compared ROSC among patients treated with 300 mg amiodarone or an equal volume of Polysorbate 80. Polysorbate 80 is a diluent in amiodarone that appears to cause bradycardia and hypotension, so it is not appropriate as a placebo.
Wow! That’s Effective!
There was a statistically significant difference in ROSC. 44 percent (108 of 246) of the amiodarone group and 34 percent (89 of 258) in the placebo group had ROSC for a p value of 0.03.
There was not a statistically significant difference in survival to discharge – 13.4 percent (33 of 246) of the amiodarone group and 13.2 percent (34 of 258) of the
Polysorbate 80 placebo group.
Yawn. That’s NOT Effective.
Of the 504 study patients, 67 (13 percent) were discharged alive from the hospital. Of the remaining 130 patients who were admitted to the hospital, 13 patients awakened, and 117 (90 percent) never regained consciousness.
Since the best outcome for 90% of these patients was a short-term coma, followed by death, was this result of a single study appropriate to change the standard of care?
More patients had ROSC, but none of them survived to discharge.
ROSC is the wrong goal.
The standard of care was changed based on this single study that did not show any improvement that mattered.
Wyeth stated that they were studying the effect of amiodarone on survival to discharge, but after becoming the standard of care, Wyeth had no reason to publish a study that did not show improved outcomes with
Brandon Oto mentions this 13 1/2 minute presentation by Dr. Ben Goldacre at Ted Talks, which is very good to watch.
A better, much more informative 1 1/2 hour presentation by Dr. Goldacre is available at CSPAN –
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text from Circulation.
The adverse hemodynamic effects of the IV formulation of amiodarone are attributed to vasoactive solvents (polysorbate 80 and benzyl alcohol).
 Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation.
Kudenchuk PJ, Cobb LA, Copass MK, Cummins RO, Doherty AM, Fahrenbruch CE, Hallstrom AP, Murray WA, Olsufka M, Walsh T.
N Engl J Med. 1999 Sep 16;341(12):871-8.
PMID: 10486418 [PubMed - indexed for MEDLINE]
Kudenchuk, P., Cobb, L., Copass, M., Cummins, R., Doherty, A., Fahrenbruch, C., Hallstrom, A., Murray, W., Olsufka, M., & Walsh, T. (1999). Amiodarone for Resuscitation after Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation New England Journal of Medicine, 341 (12), 871-878 DOI: 10.1056/NEJM199909163411203