Poor report by Scott Pelley on "60 Minutes" about Trasylol

[question everything]

First, a disclaimer. I have never been associated with the FDA, Bayer or any hospital. I am not a physician. In the beginning of my career I worked for a regulated company but was not in that department, and about 15 years ago I researched the work of the FDA - for my own information.

First, the surgeon of the man whose case was presented commented that the Trasylol caused the embolism. If he was aware of such a connection, why did he use that drug?

Second, the "expert" claimed that the FDA does not assure safety of drugs. Pelley kept asking him and the guy kept saying that the FDA only looks at efficacy. This is wrong. The 1938 FDA Act specifically required new drugs to be shown safe before marketing. After the Tahlidomide scare (even though the existing regulations kept it out of our shores) the Kefauver-Harris Amendment added the required efficacy.

If the FDA would not talk to them about that specific case, they could have still asked a spokesperson about the requirement for safety, or simply talk to any drug manufacturer to find out how they submit product registration. Pelley would have found that the first step is a safety test.

Perhaps because of this comment I doubt the last claim of that expert, that 1,000 people a month die from this drug. This, by the way, was the subject of the report. Pelley should have asked him how he calculated that number.

Again, I have no interest in any of the "players" and I certainly have no love for the FDA, with its rigid regulations that ignore the facts that in nature there is synergy and not always one active ingredient. But I think that that story was short on important facts an long on sensationalism.

http://www.cbsnews.com/stories/2008/02/14/60minutes/main3831900.shtml

[Deja Q]

1. I've seen him do reports before. He is a one-sided charlatan who eats sensationalism for breakfast.

Anything he covers is not taken with a grain of salt by me...

Try a bucket full of salt.

[question everything]

5. Interesting. I normally do not pay attention to the specific reporter

in the old days all of them were equally quite competent, now we have Katie Couric..

[cbayer]

6. Her Clinton interview last week was embarassing. nt.

[cbayer]

2. Medical pieces on 60 minutes always get my dander up.

They tend to be sensationalist pieces short on facts and long on innuendo.

My husband, who calls 60 minutes "church", wants to gag me whenever they do one of these because i start shouting at them about all of their inaccuracies.

and even though i have bayer in my name, i am not affiliated with the company. if i were, i suppose my life would be quite different.

[Deja Q]

3. "long on innuendo"

*snort*
:rofl:

[cbayer]

4. What did i say?? OMG, did i make a joke and not even know? nt.

[Postman]

7. 60 Minutes has increasingly become a joke. Scott Pelly in particular.

N/t

[hlthe2b]

8. The language re: safety testing was very inprecise...

There are typically three pre-licensure phases to a clinical trial (and yes, I have participated in conducting them), when safety is assessed via animal data, and from small to larger groups of human subjects as described on the FDA website and summarized below. However, Phase IV, which continues to look at more rare side effects and adverse outcomes are not always conducted; however, when enough people worldwide have been exposed to the drug, these more rare complications come to light. This is not the first drug to have these serious complications come to light, only when many many people have had the drug-- e.g., remember Phen-Fen in weight control which became linked to valvular heart disease?


As for your comment that questioned why the surgeon used the drug if he realized it was linked to embolism.... Apparently he did not know of the link, but only in retrospect--as similar cases began to be reported in the literature as case studies did he come to this conclusion.

Having said that, I agree Pelley's reporting on this and other stories is not up to par.

*************************************
A bit of a primer on Phase I-IV Clinical Trials: http://www.fda.gov/FDAC/features/2003/503_trial.html
Done at hospitals and research centers around the country, clinical trials are conducted in phases. Phase 1 trials try to determine dosing, document how a drug is metabolized and excreted, and identify acute side effects. Usually, a small number of healthy volunteers (between 20 and 80) are used in Phase 1 trials.

Phase 2 trials include more participants (about 100-300) who have the disease or condition that the product potentially could treat. In Phase 2 trials, researchers seek to gather further safety data and preliminary evidence of the drug's beneficial effects (efficacy), and they develop and refine research methods for future trials with this drug. If the Phase 2 trials indicate that the drug may be effective--and the risks are considered acceptable, given the observed efficacy and the severity of the disease--the drug moves to Phase 3.

In Phase 3 trials, the drug is studied in a larger number of people with the disease (approximately 1,000-3,000). This phase further tests the product's effectiveness, monitors side effects, and, in some cases, compares the product's effects to a standard treatment, if one is already available. As more and more participants are tested over longer periods of time, the less common side effects are more likely to be revealed.

Sometimes, Phase 4 trials are conducted after a product is already approved and on the market to find out more about the treatment's long-term risks, benefits, and optimal use, or to test the product in different populations of people, such as children.

[question everything]

14. Thank you for the details

Pelley kept asking his expert - don't recall his name - doesn't the FDA first test for safety? And his guest said: only for efficacy.

And Pelley asked this twice and got the same response.

If Pelley was so certain, as he should, he should have sought additional opinions.

[jtrockville]

9. FDA considers "industry", not the public, to be their client

according to quite a few sources (emphasis mine):

... Since the inception of user fees in the early 1990's, the FDA has treated drug industry as a "client," instead of a regulated entity. ...
-Congressman Maurice Hinchey
http://www.house.gov/hinchey/issues/fda_reformbill.shtml

... As currently configured, the FDA is not able to adequately protect the American public. It's more interested in protecting the interests of industry. It views industry as its client, and the client is someone whose interest you represent. Unfortunately, that is the way the FDA is currently structured. Within the Center for Drug Evaluation and Research about 80 percent of the resources are geared towards the approval of new drugs and 20 percent is for everything else. Drug safety is about five percent. The “gorilla in the living room” is new drugs and approval. Congress has not only created that structure, they have also worsened that structure through the PDUFA, the Prescription Drug User Fee Act, by which drug companies pay money to the FDA so they will review and approve its drug. So you have that conflict as well. ...
-Dr. David Graham, senior drug safety researcher at the FDA
http://www.icspp.org/index.php?option=com_content&task=view&id=129&Itemid=71

...The pharmaceutical industry's influence gets exerted in a number of ways. One, starting 10 years ago (with the Prescription Drug User Fee Act (PDUFA){, the influence was exerted by their directly funding, paying cash right up front, for FDA review. So in many ways, the FDA started looking upon the industry as their client, instead of the public and the public health, which should be the client. ...
-Sidney Wolf, M.D., Director of Public Citizen's Health Research Group since its founding in 1971.
http://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/independent.html

[hlthe2b]

10. Yes... Most of the public thinks FDA does independent testing...

THEY DO NOT. The system is reliant on honest reporting provided by those conducting the testing, which is reviewed by expert staff at FDA. Many times they can detect if something looks "screwy" in the findings, but as seen here, industry can become suspicious of a problem post licensure, and sit on the data until a whistle blower emerges or independent studies (or reports of possible associated death or serious adverse outcomes) come to light...

[jtrockville]

11. Also, the testing is focused on efficacy, not safety.

[hlthe2b]

12. Primary safety testing is in Phase I and the pre-clinical aspects

Phase II and III-- is comparative safety against a placebo (or in some cases comparative drug) group. But, as I try to point out in my post above, many serious adverse outcomes are too rare to show up until potentially millions have received the drug and hence, outside of clinical trials. THAT is what Pelley was trying to point out--however ineffectively.

[jtrockville]

13. Thanks. You clarified it better than Pelley.

[RamboLiberal]

15. But the drug was pulled and the FDA issued a warning

So there is something there. I saw no problem with this report.

Posted 11/5/07
MONDAY, Nov. 5 (HealthDay News) -- Bayer AG suspended worldwide sales of Trasylol, a clotting drug using during heart surgery to prevent bleeding, on Monday following a request from the U.S. Food and Drug Administration to remove the drug from the American market for safety reasons.

The FDA cannot identify a patient population in which the use of Trasylol (aprotinin) outweighs the risk, Dr. John K. Jenkins, director of the FDA's Office of New Drugs, said at an early morning news conference Monday.

However, he added, "the suspension will include a slow phase-out of Trasylol from the marketplace to decrease the possibility of shortages of the alternative drugs." And he added that Bayer could continue to supply the drug if physicians can identify specific patients who would benefit from it.

"Studies have found that Trasylol can increase the risk of kidney damage compared with other drugs," Dr. Gerald Dal Pan, the FDA's director of the Office of Surveillance and Epidemiology, said during the news conference.


http://health.usnews.com/usnews/health/healthday/071105/trasylol-pulled-from-worldwide-market.htm

On January 26, 2006, The New England Journal of Medicine (NEJM) published an article by Mangano et al. reporting an association of Trasylol (aprotinin injection) with serious renal toxicity and ischemic events (myocardial infarction and stroke) in patients undergoing coronary artery bypass grafting surgery (CABG). Another publication (Transfusion, on-line edition, January 20, 2006, Karkouti, et al.) suggests an association between aprotinin administration and renal toxicity among patients undergoing cardiac surgery with cardiopulmonary bypass. FDA is evaluating these studies, along with other studies in the literature and reports submitted to the FDA through the MedWatch program, to determine if labeling changes or other actions are warranted.

While FDA is continuing its evaluation, we are providing the following recommendations to healthcare providers and patients:

Physicians who use Trasylol should carefully monitor patients for the occurrence of toxicity, particularly to the kidneys, heart, or central nervous system and promptly report adverse event information to Bayer, the drug manufacturer, or to the FDA MedWatch program, as described at the end of this advisory.
Physicians should consider limiting Trasylol use to those situations where the clinical benefit of reduced blood loss is essential to medical management of the patient and outweighs the potential risks.

http://www.fda.gov/CDER/DRUG/advisory/aprotinin.htm

[hlthe2b]

16. ABSOLUTELY, there is something THERE, as you say...

The report was very poorly done, but that does not change the message. This drug is bad news. I think you misunderstand the gist of many, if not most of the posts here...