December 19, 2008

What I'd Like to See Change at the FDA

The FDA announced some changes in how it will approve drugs for Type 2 diabetes which have sparked controversy in the diabetes community. Unlike many, I believe this is good news, not bad. A fellow diabetes activist asked me what I would like to see changed in the FDA and I wrote him a reply which I am sharing with you here.

The most important thing I'd like to see change at the FDA is going to happen without our needing to submit petitions: restoring science as a criteria for drug approval. The Bush FDA was notorious for the way that decisions were made based on financial connections of FDA staff to drug makers and their religious beliefs. But beyond that I think the following are most important:

1. End "direct to consumer" drug advertisements. These are well-known to be full of lies, but it takes so many months until an ad is shut down for false claims that these lies cando their work.

2. Make drug testing compare a new drug with the safe, cheap existing drugs. If there is no significant benefit compared to safe, cheap drugs, do not approve the drug. Right now, most drugs are only compared to placebo. So a new drug that is no more effective than a safe, cheap proven drug but costs 20 times more per pill gets approved with huge fanfare and becomes the subject of a billion dollar advertising campaign that gets doctors switching patients to it from the safe cheap drug.

3. Do not let drug companies claim a drug "rejuvenates beta cells" until this has been proven by direct measurement in humans. Every single such claim for a drug in the past, which included the major claim used to market Avandia, has been based on surrogates like HOMA measurements which turn out to be a false guide or on findings in rodents which did not extend to humans.

After a decade we finally saw research that showed conclusive evidence that Avandia did NOT rejuvenate beta cells. But for a decade doctors prescribed it on that premise.

Currently Januvia and Byetta are being sold with the same claim, based only on test tube and rodent studies. This motivates doctors to keep people on these drugs EVEN when their blood sugars are deteriorating and they are experiencing severe side effects. The long term deterioration in blood sugars experienced by people who are taking Byetta long-term suggests that just like Avandia, it does not rejuvenate beta cells. But doctors continue to tell patients it does.

4. When a new designer drug is targeting a gene or specific receptor, the approval process MUST included investigation of the other uses of that gene or receptor and the impact of the drug on those other functions must be explored.

The dangerous side effects of ALL drugs from sulfonylureas to Avandia to Januvia turned out to be caused by the OTHER functions of the genes or receptors they target. There is currently NO requirement in the testing process that the drug company do this. The technology for exploring gene expression has advanced greatly and the cost of this kind of research has dropped dramatically. It is now very possible to see which genes are expressing in response to different stimuli. It is possible to see which receptors are accepting a drug.

We can no longer approve 21st century drugs only with techniques developed in the first half of the 20th century.

People who have not been prescribed the drugs given to people with Type 2 diabetes can have little idea how dreadful the many side effects of Type 2 drugs really are.

But many patients trust their doctors completely, and if the doctor gives them a drug, no matter how awful it makes them feel, they take it, especially if they have been told, as many have, that the drug is "regrowing their beta cells."

Their reward for this may be enormous weight gain, osteoporosis, and even blindness (Actos and Avandia), heart attack (Avandia, Glipizide), pancreatitis (Byetta), irreversible inflammation syndromes or cancer (Januvia.)

I get heartbreaking emails from people who have suffered these permanent side effects. They are very real. I myself live every day with a miserable permanent side effect of a prescription drug. So I would far rather that a drug not be approved, than that it be "fast-tracked", sold to hundreds of thousands of people, and worsen their lives. Especially when there are already other drugs that work just as well.

To the argument that making drug approval harder will stifle drug development, I say only, look at the profits on a single successful drug. As long as a company can earn $200 a month from a vial of 30 pills or 60 units of an injectable drug, drug development will continue.

As it is, the drug companies are not doing new research. They are putting most of their efforts into making tiny changes to existing drugs to keep them under patent or into developing copycat versions of drugs sold by other companies. If the incentive to copy other drugs were lost, we might actually see new drugs coming in the pipeline, which is far from the case now.

8 comments:

SnowDog said...

Ah Jenny, you want to use force in so many different ways. Don't you know that force is backed by threats of violence at the point of a gun?

Let people say what they want, test the way they want, and claim whatever they want. Don't hinder new drugs from coming to market. If people lie or make false claims, this information will get into the market too; those responsible will lose their reputation, and fraud has always been a crime.

Jenny said...

SnowDog,

"If people lie or make false claims this information will get into the market too".

It took 10 years for the news that Avandia causes irreversible osteoporosis to hit the market--this is going to kill a lot of older women.

It will take at least that long for doctors to realize that Januvia energizes cancer.

Thousands of people may die unnecessary during the decade while drug companies profit. Even with Rezulin, hundreds of people ended up with liver failure who need not have, had the drug company acted more responsibly.

Nothing will bring back the people who die unnecessarily. When they die unnecessarily taking a drug that makes only a tiny difference in their blood sugars as is the case with TZDs, the tragedy is that much more unnecessary.

Anonymous said...

New Year's Resolution: Watch and think about "Sweet Misery." This was shown recently on the Documentary Channel. It is so perverse, and because aspartame is such a godsend for diabetics longing for a 'taste of sweet' without the penalties, it seems they are doubly victimized.

The 'market' may take care of false advertising and pseudo-science . . . but how many are harmed in the meantime.

--Melody

Anonymous said...

Jenny, I can't help but notice that you are not a fan of TZD's at all. I agree that Avandia should have been taken off the market in 1999. However, Actos, I believe is a far far superior drug. You said,"When they die unnecessarily taking a drug that makes only a tiny difference in their blood sugars as is the case with TZDs," What drug has a better A1C drop then Actos, and for as long? You wrote quite a bit bashing both Actos and Avandia, citing a ton of studies, but I couldn't help but notice you didn't mention the ProActive study. It showed huge reductions in heart attack, stroke and all cause mortality, and it consisted of over 5200 patients who already had a macrovascular event. There is no other drug with even close to similar data. Or the Periscope Study, which showed a possible reversal of coronary atherosclerosis. And Actos is the only oral anti-diabetic drug with FDA approved safety data included in the PI. The only one. So when you say that their are safer drugs, which ones exactly are you referring too? So, with all this data, how do you lump it together with Avandia and say that it's just as dangerous, when clearly it is not. And it is all too painfully obvious that the other drugs available are not able to deal effectively with such a progressive disease. I'm not saying Actos is perfect, or for everyone, but I believe it is definitely one of the best choices available.

Jenny said...

Counteracting the studies you cite (which I have not been able to read in full text to see exactly how they were conducted and to what extent they were controlled by Takeda) are those that show that Actos CAUSES heart failure in younger people who were fine before they started it, that it increases the likelihood of retinal edema (which leads to blindness) and that it causes bone bone fractures over time, which in older women is a major cause of death.

There are several other drugs that lower A1c to the same extent, including metformin, byetta in those who response to it, prandin, and sulfonylureas.

A low carb diet will reduce A1c by two or three times as much without the threat of damaging organs permanently

Anonymous said...

Actos can lower A1C up to 2.6% points. With Metformin, and Byetta your looking around 1.5%. Sulfonylureas can get you close to a 2% drop, but then you have to deal with bouts of hypoglycemia which can be very dangerous, and sulfs also contribute to an accelerated drop in beta cell function. Byetta increases your risk of pancreatitis, and the last few instances of pancreatitis have been fatal because they were cases of necrotizing and hemorrhagic pancreatitis. Not to mention that byetta jsut hit the market and haven't even completed a macrovascular outcomes trial. So, honestly how can anyone say they are safe?
The trial I was referring to earlier called the ProActive trial was completed in Europe. I'm sure it was funded by Takeda, but nowadays doctors aren't going to do research out of the kindness of their hearts and then hope that the pharm co pays them later for tehir troubles. You should take a look at it. The results are pretty amazing. As far as CHF, many drugs contribute towards CHF in all age groups (insulin and sulf's for instance can also lead to peripheral edema which can cause or exacerbate CHF.) In the ProActive trail there was a greater occurence of hospitalization due to Serious heart failure in the Actos arm, but the instances of death from that heart failure was 1.6% in the Actos group and 1.5% in the placebo group.

Jenny said...

Anonymous,

The lowering of A1c after 26 weeks reported in the official Actos prescribing information is .3 to .8% in a population whose average A1c was 10%.

The very small number of deaths from pancreatitis found with Byetta--6, and it is not clear if there is causation, palls next to the deaths from unnecessary heart failure from Actos.

There is no such thing as "mild" heart failure. It is fatal within a period of time longer than the study you cite.

You really need to tell your bosses at the lobbying firm promoting Actos to give you better data. And please post any further rebuttals from a non-anonymous ID so we can see who you really are.

Anonymous said...

First, in the study you are referring to it was actually .9%.

Second, what makes you think Byetta is so safe? They haven't completed a macrovascular outcomes trial, and they have no fda approved safety data in their PI. Is it really a good idea to take a drug just because nothing has been reported yet? Ignorance is not always bliss.

Thirdly, there is such a thing as mild heart failure. It's simply a matter of ejection fraction.

Lastly, I don't work for a lobby firm and no one "gives" me any data. I look it up freely on the internet because I choose to. The really sad thing that I can't figure out is why do you only choose to post the negative things about drugs you dislike and positive things about drugs that you obviously favor? If you think about it. There are a lot of desperate type 2 diabetics out there who are fairly naive and haven't really educated themselves about their disease. And by reporting only the things you choose to report, you are manipulating them in roughly the same manner that the big pharma companies manipulate them. Don't you think it would be better to lay everything on the table, both good and bad, and let people decide for themselves?

I prefer to remain anonymous. I would comply (although, not understand) if you would like me to refrain from commenting because of this.

Believe it or not, I have enjoyed our dialogue. I think a lot can be learned from a open minded debate.