I am confused about the recent actions regarding pain killing drugs (such as VIOXX). Firsts, I believe that the US FDA dictates that drugs should be “safe and effective”. Leaving the interpretation of this phrase aside, I would assume that any new drug should work (provide its benefit), and not have serious side effects.
Suppose (purely hypothetical case here), that your company has just discovered a new drug that treats HIV/AIDS. It works great-it CURES the disease in 50% of the cases…the other 40% experienece either severe side effects (including death); or illness plus no remediation of the disease.
What would be done with such a drug? Would the company conclude:
(a) the drug is too dangerous and will not be manufactured?, or
(b) the drug will be manufactured; however, the company must seek waivers 9from the users), tolimit liability?
From what I read, VIOXX was very effective in treating arthritis pains. However, it did have very serious side effects(in 10-15% of the population). Does this constitute a worthwhile risk to a potential user?
(a) the drug is too dangerous and will not be manufactured?
Well, this is precisely what the FDA is for. Any drug is going to have some side effects and is going to be less than 100% effective. There are already drugs on the market that have very very severe side effects but are approved to treat even more serious diseases. Many AIDS drugs, for instance, do horrible things to the patients. Or how about chemotherapy for cancer, where the idea is to kill the cancer cells just slightly faster than you kill the patient? It’s the FDA’s job to balance the good with the bad and decide if the one offsets the other or not.
Incidentally, my biochemistry professor told us that if aspirin were just now being discovered, there’s no way the FDA would approve it as an OTC analgesic, because of the stomach problems it causes.
Could you clarify what you mean by this statement. Do you believe 10-15% of the population were potentially at risk for serious side effects from Vioxx use, or that 10-15% of Vioxx users would have serious side effects? They are very different statements, and actually I think but are wrong to some degree/
I think in Merck’s big GI safety trial (the VIGOR) trial it was shown that Vioxx had a statitically significant higher rate of heart attack than the control group (0.5% vs 0.1%), with no significant difference in cardiovascular mortality.
What people need to remember is that any drug works by doing something to your body that your body wasn’t doing “naturally”. Every drug has at least potential side effects. With every drug there is the question of benefit vs risk.
The COX-2 drugs offered potential gastrointestinal benefits to a *portion * of the population. However, they quickly became the arthritis pain drug of choice for the majority of the population. I guess you could say that the benefit/risk question was somewhat ignored in this case. For those people with or susceptible to ulcers, the trade-off probably tilted towards the COX-2s offering more benefit than risk. For everyone else, who knows?
I think Merck likely didn’t habdle the Vioxx safety data well, but I also personally think it wasn’t necessary to pull the drug off the market.
Disclosure: I’ve worked in the pharma industry for about 10 years, but not for Merck.
Oh, and to actually answer the OP. In the past, I could see that hypothetical drug being approved for usage limited to end stage AIDS patients.
Today, after the Vioxx thing, the FDA would shoot you if you walked in the door.
At this point in time, the FDA has absolutely zero incentive to approve any drug, no matter what it cures. We’ll see how long that lasts.
Hey, it’s not like Vioxx was saving lives. It wasn’t even a particularly better or safer pain-killer. So the issue here was “reduce non-life/health threatening pain as well as other drugs, but with a higher risk of death”.
Vioxx wasn’t particularly better at reducing GI bleeds vs. older meds, either.
Your last statement is where you go astray.
There are many drugs with extremely serious side effects that are, nonetheless, approved for use and used every day.
It’s a matter of risk vs. benefit. The seriousness of the disease also has an impact.
Side effects that would be intolerable in, say, a cold remedy or for use in minor infections are used routinely for treatment of life-threatening diseases such as cancer. One of the antibiotics used for treating certain types of meningitis almost always causes hearing damage of some sort, and sometimes complete deafness. Some of the medications used to treat life-threatening septic shock can lead to the loss of fingers, toes, and even more of the extremeties. The reason this is OK, in the sense of approved and legal, is that death is usually seen as a worse outcome than damaged hearing or the loss of your toes, however inconvenient those “side effects” may be to you, personally. Of course, we’d all prefer less toxic means to save lives, but sometimes the best we can do is far from perfect.
For someone who is truly crippled with arthritis, to the point of being unable to care for themselves, a trade off of a slightly higher risk of heart attack for being able to live a normal life again might be worth it. However, Vioxx and cousins really never were more effective than asprin in relieving pain - their main selling point was less gastrointestinal irritation. The vast majority of people who had been taking them should have been on asprin, which is heart-protective, and which they did not need in quantities large enough to put them at high risk for GI problems. Only those who did need large doses of asprin, or who were at usually high risk of GI complications, should ever have been on Vioxx.
A lot of this has to do with over-selling a drug, and people automatically assuming new is better.
Yah, know, Dr M, I think this is the first time I’ve questioned you on a statement regarding medicine, but since evidence-based medicine (EBM) is the stock in trade where I work…
In fact, Vioxx does have less risk of inducing GI complications, including bleeds, than asprin. Not a whole lot less risk, but somewhat less risk which, for those already at high risk of a bleed, but also requiring arthritis medication, made it worth considering. Until this business about increased risk of heat attack came out and skewed the risk vs. benefit equations. And yes, there are drugs other than asprin which relieve pain and have less risk than asprin of GI problems.
The real crime here, IMO, is that the information on increased risk to the heart was there, but kept under wraps. You can’t make an informed decision, and neither can your doctor, if you don’t have access to all the information that’s out there.
The other thing that’s been cranking the handles of the EBM crowd is the perception among the public that Vioxx and other Cox-2 inhibitors produced superior pain relief, which it most certainly did not - which impression the drug companies did absolutely nothing to discourage. Of course not - it was helping sell the drug.
Less risk than aspirin, yes. Aspirin is such a horrible drug for the GI tract (not to mention that it’s toxic range is damn close to it’s therapeutic range for inflammation) that if introduced today, it’d never get approved.
But when compared to Salsalate, trilsate, feldene, and even sulindac, I’m not sure there was really any statistically significant reduction in the risk of GI bleeding, based on the studies I’ve seen. Tho I admit I’ve not combed the literature to make sure I’ve seen them all.
And for the appropriately selected patient, I still think Cox-II has a role. But that patient represents about 1/10 of 1% of all patients who got put on Cox-II. IMHO.
I think we’re in agreement about the “properly selected patient”… but the pharma company(s) couldn’t make a decent profit off such a small sub-set of pain patients, so they fudged a little in the advertising. Didn’t exactly lie, but didn’t tell the whole truth either…
Personally, when given a choice between old-known-quantity and new-hot-medication, I’ll go with the old standard, all other things being equal. But that’s probably not how most people think.