Got a patent for drug combinations on cardiovascular disease? How about "proving" everyone needs the drug...

[Click on the following for Link to External Article]

Click here for the Medscape Article

The actual study is here:

Click Here

The Premise

Call me a skeptic, call me rude, call me anything you want..But having seen and known too much about conflicts of interest and bias in clinical trials and studies, I become suspicious, especially so when I see small studies and more importantly "meta analyses" make broad stroke recommendations.

Thus when I saw a study that said "Feed all old people anti-hypertensives", I became wary. Alright, the title of the article was a little less crude, I admit. But, nevertheless, it did not please me. Let's examine some quick facts:

Some notes on the study

1. The study examined data from 147 clinical trials conducted over 40 years.

2. The study concluded that all 5 major classes of anti-hypertensives seemed to reduce the risk of cardiovascular events regardless of the patients' history with respect to either prior cardiovascular events/risk or hypertension.

3. How much of a reduction in pressure where they looking for? A 10mm mercury reduction in systolic and 5mm in diastolic pressures.

Results, Conclusions and Recommendations

The study results do look good, just like they do in meta-analyses. After all, you are not directly studying something, just looking for what you would like to see.

People with hypertension are definitely on their path to cardiovascular events. The real difference comes from a combination of hypertension and other factors.

What is the real gripe?

The studies should have focused on reducing hypertension, and consequentially, cardiovascular events in patient populations pre-disposed to hypertensive and cardiac disease. If the 22% reduction in coronary artery disease and 44% reduction in stroke was comparable in both groups, how can we actually assume that patients who we consider not pre-disposed to CV/hypertensive were indeed not actually pre-disposed to the disease?

Well, there can only be one of three answers:

1. That, in these studies, at a broad level, folks who were not considered "at risk" were indeed at risk, and 147 studies were designed poorly. Okay, that is an extreme position to take, but at least some of the studies should be wrong, right?

If not, shouldn't you see a comparable decrease in CV events in patients/controls considered not "at risk"? Well, let's consider the other possibilities.

2. It is quite possible that the controls who were not considered "at risk" would have not really taken good care of their health. They let their life styles slip and as a result, ended up with cardiovascular disease.

3. Since at least some of these studies were treating patients for other factors, such as cholesterol, it is possible that they had a role to play in disease mitigation and the 22% and the 41% might have been influenced by the study population being treated for other conditions - see the problem with "large" and "comprehensive" meta analysis?

The Conclusion and a Side Note

Anyway, at the end of it all, when I came down to the article's end, I found out that the scientists involved in the study, who recommended (albeit with warnings on the fringe about drug combinations) that every "older adult" should be asked to take anti-hypertensive medicine actually own patents on drug combinations...

You can conclude the rest for yourself, but I am no Doctor, and still, I am going to try the "lifestyle change". I really think the idea of popping anti-hypertensives after I reach my "older adult" stage sucks. If that is what I am looking for, I might as well harm my already poor lifestyle a tad bit more...

Other problems?


1. What about people prone to low blood pressure? What if some company thinks it is a great idea to make blood pressure medicines to be a "dietary supplement" and someone prone to lower blood pressure accidentally takes it?

2. Hmm, have you thought about side effects of blood pressure meds before telling the world to take 'em?

A side note: Was aspirin also gold-standardized in a similar manner for all "older adults"?

You know, with the new wave of recommendations on hypertension coming from the old world on the basis of some extremely strong metanalysis, I got to wondering if Aspirin was also pushed on us in a similar manner. Remember when Bayer wanted to call Aspirin a "Dietary Supplement"?

Well, it does not appear to be as flimsy as the anti-hypertensives:

http://circ.ahajournals.org/cgi/content/full/96/8/2751

The AHA seems to have done a fair job, with 22,071 male physicians testing themselves with aspirin as an alternate therapy, resulting in a 44% reduction in MI. Of course, given they are physicians and knew about hypertension, hyperlipidimia (fancy for High Cholesterol) and smoking, maybe, just maybe some of them made "lifestyle changes".

Somewhat comforting, eh?

Abbott the innocent fires Harrison the unrepentent? ...And some very disappointingly minimal actions by Obama

[Click on Post Title for Link to External Article]

If I were the lion from Narnia, I would name Abbott, "Abbott the innocent", that is, if my taxonomy went solely on the basis of companies' ostensible acts. Of course, I am not the lion of Narnia, and no one else should be buying this load of Humira either...

One classic political strategy used in many situations is - assuming the one to yell out loud and clear first is the one to blame.

Except, ahem, we understand politics. And it is "classic" which means old. How many Lucille Ball show endings surprise you anymore?

Here are some questions someone might have to put to the innocents here:

1. Do you review the ads that get put out for $70 million on your behalf?

If not, you are either too rich or, well you are you.

2. If you did review the ads, did you not check for the most fundamental aspect of what approval conditions the ad hints at? Examine this - you don't really get people with science education working for ad companies much. I would imagine not...

So, how did the decision to leave the final proofing for an ad to be displayed in a medical journal get left in the hands of an ad agency? Was the expectation that the ad agency would go hire some outside consultant that would clarify the language on FDA approvals?

If so, who thought that this was a great idea?

3. So, are we to assume, the ad agency, acting on its own poorly conceived cognizance decided to make the fine print, so fine that it is a blur at best, that even if, as suggested by bnet.com, you were to zoom in to 100% or more, the pink vs. white would nearly blind you?

May the cat-belling ceremonies begin

Alright, as another cliche goes, enough beating around the proverbial bush. What responsibility, if any is Abbott going to presume? What punishment if any, is the FDA going to dole out? I mean, the damage is done - right? People have already viewed the ad right? (This presuming those who read journals are incredibly stupid and will trust everything at face value - just ask those who invested in Wall Street).

An analysis

1. The Politics

So, for the last 8 years or so, we can argue, for certain inexplicable reasons (The Bush Presidency if that's what you want to call it), the FDA has been "Deadbeat Central". And now, we have hope and change.

Except it is coming at such a deliberate pace that our hoping and changing seems to need some "extreme enema". The FDA is headless (as of Saturday morning, it has a prospective head and a deputy, provided they have managed to pay taxes, something that Obama nominees have a chronic problem dealing with). Only the God (and not evolution because every alternate opinion, however incredible needs support) knows how much tax-paying and withdrawing drama the nominees will finally bring before they start at the FDA.

2. The Supreme Court

Meanwhile in a far, far galaxy, unkown to Obama and Pelosi (because they are too busy organizing Healthcare summits - because talking rather than doing your job is indeed the best way to get the job done!), the Supreme Court and other agents of spontaneous change will continue to constrict us. How did they figure that pre-emption works only for devices and not drugs?

Is the intention to demonstrate the FDA is good enough only for devices and not drugs? Or did they decided to demonstrate that they are so far removed from the lofty quanta of intellect and depth of understanding required for being at a minimum, a district court judge? Don't they have the responsibility to explain this mess they are leaving us in?

Or did I miss the memo that they don't have to? Looks Cheney-istic, n'est pas?

3. The joke FDA

To pre-empt or not pre-empt - is not the question. In every single way possible, the FDA has demonstrated its incapability at administering anything.

Wait, didn't they just yell at Yaz and Abbott?

Heard of too little, too late?

If no one remembers (and given our short term memory, no one does), here are a few things that the FDA has done to win accolades in the recent past, read my previous post here:

1. The website that the FDA put together on DTC ads to "inform" consumers was designed by a "non-profit" (which of course helps put all the good non-profits to shame) that is a front for the mob, er, pharmaceutical companies. This just makes me sound like one of those Area 51 conspiracy freaks, but this is real! :

http://www.pharmalot.com/2008/09/fda-tapped-pharma-consultant-for-dtc-web-site/

2. They have been so ineffective that companies openly disrespect them - before warning Bayer, the FDA did indicate to them that there was trouble brewing. Bayer didn't care. Take a look at the DTC ads by "Dr." Jarvik and how much pain even Congress had to go through to take him off air (yes, I was one of the folks duped by the ads with him as well, and I am still smarting!).

This is new:

3. Bayer misled customers on Yaz and it's capabilities. The FDA entered into an "agreement" with Bayer asking for a minor correction in the ad - something that appeared fleetingly and is nowhere to be seen. Of course, after the initial celebration of a watered down, ineffective response, no one is talking about it anymore:

http://www.medicalnewstoday.com/articles/138729.php

So, where does this all lead? It goes back to the same topic - the FDA, it's inherent weakness and the unwillingness of lawmakers to do anything about it.

Should we simply complain or come up with a strategy?

Yes, there are several strategies that can be employed - the least effective of which is the one President Obama wishes to employ: blindly continue the same course for the FDA and simply hope that dumping cash and new leadership on a dead mechanism will somehow fix things. Which, is exactly what he has done today. Given the level of promise for change, disappointment and frustration are on the rise.

Here are a few things Obama and Congress can do, at least in the future:

1. Stop thinking linearly as far as the FDA goes. In today's speech, Obama's primary focus was on food, probably motivated by the salmonella outbreaks. However, the FDA regulates much more - drugs, devices, food and a whole array of things. Today's speech confirms that even the President has a poor grasp of the FDA's reach and the necessity to stem it.

One single organization cannot regulate so many aspects of health anymore. Yes, yes, we all know they have subdivisions, but we also know that has basically done nothing. Food administration has to be separated from drug and device administration.

Given the fact that drugs and devices have to be regulated together, one organization should do it. However, they should be distinguished by separate administrations with distinct leadership and separate teams.

2. "Warning letters" and "agreements"

The FDA's business is regulation, not officious groveling to businesses. This is the key point missing in how the FDA is run and how it acts today. In the case of Dr. Jarvik, the Bayer Aspirin ads or even in the case of Yaz, there should have been stricter punishments handed out.

The FDA has failed to act appropriately on all counts. They did not identify the issues at all in some cases - Dr. Jarvik was a fall out of Congress begging and groveling in front of Pfizer for information. The ads kept running for a whole while before Pfizer removed them, almost as an act of condescension, not repentance. The same goes for Bayer with their "dietary supplement nonsense".

This is why the FDA has absolutely no standing anymore. Organizations continually paint outside the boxes and sometimes the paper itself, and they have very, very little to answer for.

How is simply appointing a new head of the FDA actually going to change this? A simple change in leadership is not going to eliminate the regulatory cancer we suffer from.

The solution exists. The strategy exists. However, a lot more action is needed for implementation, bold and quick and unfortunately the President does not seem to be up to it...