Thursday, May 10, 2012

Pharma Worries

Over the weekend, I read a book by Alison Bass called Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial. It is about a 2004 lawsuit brought by the New York District Attorney against GlaxoSmithKline, in which it charged that GlaxoSmithKline had criminally withheld information about the use of Paxil for pediatric depression. GlaxoSmithKline settled out of court.

 On a larger scale, the book is about the ways in which medications get sold in the United States. It is a grim picture, at least in the time period (1990-2004) that the book really examines. Paxil in children showed no improvement on any score in tests to see if it helped kids, beyond the degree of improvement shown with placebo. The trial groups in youth also had a four times higher rate of suicide attempts (as well as violent outbursts) with a significant increase in actual suicides. In writing about Paxil, scientist doctors accepted money to write studies in which they falsified data and also used abstracts that did not agree with their data sets. Articles were accepted in peer reviewed journals despite the objections of the peers reviewing the data. Martin Keller stole hundreds of thousands of dollars in public funds as well as received hundreds of thousands of dollars from drug companies, wrote one of those fraudulent papers and has yet to go to jail or be fined or lose his job.

 In the United States, medications do not have to be shown to actually work in order to get FDA approval. They certainly don't have to be better than older medications on the market. And they can be prescribed for things they haven't been studied in correlation with and for populations for which they aren't approved (there are some drugs that are exceptions to this rule). I have read a number of books in the last few years that make me very worried and angry because they demonstrate that drugs taken by millions of Americans pose a clear and present danger to their health- without having any of the claimed effects whatsoever!

I believe I wrote a post last year after reading Mad in America: Bad Science, Bad Medicine, and the Enduring Mistreatment of the Mentally Ill by Robert Whitaker, which makes the shocking claim that mental illnesses diagnosed prior to the "antipsychotic" prescriptions had staggeringly higher rates of remission and that studies of "antipsychotic" medications are done in extremely unethical and unscientific ways, by people paid large sums of money. Schizophrenics in countries where antipsychotics are unavailable or less likely to be used have those same high remission rates observed in the United States a hundred years ago (this really hit home because I had just read a book about the insane asylum established in Illinois at the urging of Dorothea Dix in the mid nineteenth century. It boasted a cure rate of greater than 50%).

 Although I have primarily read about medication misinformation around drugs for psychiatric issues (the mentally ill are in many ways a uniquely vulnerable population), medical misinformation disseminated to further the interests of big pharma does not stop there. Anybody who reads much in the medical journals about new therapies tried for any medical condition will come across abstracts that don't agree with the data in the article. Some of this is innocent. Some of it is not. You will also find many medications or medical treatments whose benefit over another medical treatment is some bizarre endpoint that doesn't seem very important. And usually, it isn't. If you look at a hundred different outcomes, and you consider something statistically significant if the chance that it's a coincidence is less than 1% (by statistical models using normal variation- no I'm not explaining that), you can publish findings this way:
This almost certainly explains why, when a diabetes medication or treatment has no apparent benefit, I read statements like "the treatment group had better preservation of c-peptide" or "insulin antibody levels were lower in the treatment group" or "weight gain was lower in the treatment group" when the data shows, in the three articles respectively, no reduction in the primary end markers which were total insulin dose and A1c, no reduction in the primary end marker which was A1c, and that weight gain was actually only lower in very specific periods of time after starting the trial medication vs control medication- they looked at weight every two weeks and it was higher some weeks and lower other weeks. The three in question are studies on insulin pumps (vs MDI), Humalog (vs Humulin R) and Lantus (vs NPH). That drug companies are making false claims about the efficacy and safety of diabetes medications to doctors and patients is not questionable; it's a certainty.

 The very first one I noticed was right there in the prescribing information for Lantus. I'm sure y'all have heard the Lantus claim to fame; that it gives a relatively flat level of insulin action for 24 hours. Now if I wanted to test how long a medication lasted in a person (or animal), I'd keep testing their levels, say once an hour, until they stopped being measurable. Do you think this is what Sanofi Aventis did? No! (or at least, that's not what they say they did). No, what they did was take a large number of people, give them Lantus, and measure blood levels of Lantus every hour until... 24 hours. The first people in the study to stop having Lantus in their blood stopped having it there between 10 and 11 hours after the shot. The majority of people still had Lantus at a level very similar to the first hours after 24 hours. Guess what that means? It means if you are an average person taking Lantus every 24 hours, you have a time period in which you have two Lantus shots active, causing a significant difference in your Lantus levels. Surprise!

 Although there are dozens of companies making and selling insulin worldwide, only three sell insulin for humans in the United States: Lilly, Sanofi, and Novo Nordisk. All three have interesting stories that come up if you google them with the word "lawsuit", although Sanofi seems to have been sued over sex related charges to do with female pharmaceutical reps, and Novo with not paying overtime.

Having thought a lot about the dangers in medical products, one of my first instincts is to try to figure out which medications a person should be most sceptical of. Here's my list:
 - Medications that have been recently released and that do not exist in generic form. New medications are more likely to have common side effects that haven't been exposed, or that didn't reach statistically significant levels in trials. Don't take a new medication unless you want to be a guinea pig (noble of you) or it stands to make a really big difference in your life.
- Medications for which a clear need does not exist. Yes, treatments for male pattern baldness exist. One of them can also cause male infertility. Medications that have only been shown to affect proxy measures of health should be considered suspect as well. Don't take a medication to lower your cholesterol or blood pressure or blood sugar or heart disease risk if those medications haven't been shown to decrease risk of death (or at least whatever health complications you truly care about- because I'm fairly certain you wouldn't mind high blood pressure if it wasn't for the risk to your eyes and kidneys and heart- so if the medication lowers blood pressure without protecting these things, it's not doing you any good).
 -Medications that were tested and are primarily used in a population that isn't you should be suspect, especially if they are new. Be wary of a drug that is only FDA approved for lowering cholesterol if your doctor wants to prescribe it for your arthritis.
 -If your doctor has samples, beware. That means his primary education about the product almost certainly came from a pharma rep, who almost certainly sugar coated the efficacy of the medication, and not from experience, colleagues, or medical journals. It doesn't mean the product or medication is a bad thing, just somewhat suspect.
 One thing I wonder is whether or not products and medications coming from smaller companies should be given more or less trust. Little companies have less money to influence doctors and the FDA, but they have more invested in each thing they market. If it's not great, they have nothing. I don't know the answer to that one.

No comments: