Sunday, June 7, 2009

Comparative Effectiveness Can Be a Win for the Drug Companies

One of the Obama administration's major initiatives as part of health care reform is comparative effectiveness. Currently, the drug and device companies do almost all of the research. NIH and other government agencies don't often compare which treatments work best and the industry usually only sponsors studies that it knows will make their product come out on top. Thus, it is not surprising that many drug companies do not support this comparative effectiveness. However, their position may be misguided.

A great example of comparative effectiveness was just presented this afternoon at the American Diabetes Association and simultaneously published ahead of press in the New England Journal of Medicine. The trial is called BARI 2D and is a 5 year comparative effectiveness study in over 2,000 type 2 diabetics sponsored by the good old USA (via NIH). In this case, the drug companies won not just once, but twice!

1. Drugs beat interventions. BARI 2D was designed to look at two things. First, in patients with type 2 diabetes who have atherosclerosis (blocked heart arteries), do they do better with interventions like surgery (coronary artery bypass) or percutaneous coronary intervention (where the cardiologist goes in with a catheter to open up a blocked artery with a balloon, often leaving a stent in place) or no interventions and just medications. Previous studies had shown no difference between medical therapy and intervention for stable patients, but the question remained whether or not this would hold true for type 2 diabetics, who are at even higher risk for heart related events. However, the same results were seen. Optimal medical management (think lots of pills) is better than angioplasty and bypass surgery. If I was the head of a drug company, I would be pretty happy with these results.

2. New medicines beat (sort of) old medicines. The second question BARI 2D tried to answer was whether the greatest benefit in this very high risk group of type 2 diabetics would come from insulin providing medicines (insulin, sulfonylurea-which are older drugs) or insulin sensitizing medicines (metformin, and thiazolidinediones or TZD's, which are newer). Again, there was essentially no difference in the primary outcomes of death or major cardiovascular events.

Having the old drugs show no difference then then newer drugs might at first seem like a loss for the drug companies. However, severe hypoglycemia was more frequent among patients assigned to receive insulin provision than among those who received insulin sensitization.This is important, because severe hypoglycemia is bad, and can be life threatening. Even more important, at the 3-year follow-up, the most frequently used drugs in the insulin-provision group were insulin (60.7%) and sulfonylurea (52.0%); in the insulin-sensitization group, the most frequently used drugs were metformin (74.6%) and a thiazolidinedione (62.1%- of which most (55%)was rosiglitazone or Avandia). Specifically, the use of insulin was double in the insulin providing group. If you can achieve the same results without using insulin why wouldn't you? My patients don't like taking insulin. The strips are expensive, checking your blood sugar frequently has been proven to reduce your quality of life, and I already mentioned severe hypoglycemia. This is a loss for those drug companies that make insulin products, but a real win for those drug companies that make pills and other newer insulin sensitizing products. Finally, more than half of the patients in the insulin sensitizing group took Avandia and virtually none took it in the insulin providing group. Guess what? In this group of type 2 diabetics who were at extremely high risk for death and heart attacks, there was absolutely no difference. Thus, BARI 2 D trial confirms what the RECORD trial clearly showedjust the other day: there is no cardiovascular risk associated with Avandia. This is a win for GSK (makers of Avandia) and Takeda (makers of Actos, another TZD).

BARI 2D represents comparative effectiveness at work. It tells us that we should be using medicines (even if some of them are expensive) instead of doing angiography and surgery (even more expensive) in certain patients who are commonly using the later. BARI 2D also shows us that newer (even if some of them are expensive) insulin sensitizing drugs provide equal cardioprotective benefits, but less hypoglycemia and less need for insulin which has many costs associated with it. The drug companies should re-consider their stance on this issue. If they are making novel and useful products, comparative effectiveness will likely be a win for them.

ADDENDUM- In the middle of writing this post, the Wall Street Journal published Diabetes Study Questions Expensive Treatments on this exact same issue. However, they got it wrong on Avandia and Actos. These medicines were shown to provide better sugar control, less hypoglycemia, and less need for insulin. It was indeed disappointing that there was not a statistically significant reduction in death or cardiovascular events. It is possible that longer studies would be needed to show this effect. However, even with no difference in the primary outcome; better glucose control, less hypoglycemia and less use of insulin is a win for these medications, not a loss.


Mr. MedSaver said...

Comparative effectiveness will kill Big Pharma. Want proof? Look at the Top 200 Brand-Name Drugs of 2008:

Dr. Matthew Mintz said...

yes and no.
Let's just look at the top 10: Lipitor, Nexxium, Lexapro, Singulair, Plavix, Synthroid, Prevacid, Advair, Effexor, and Diovan.
Lipitor is not only more effective then generic simvistatin, but does things that even the maximal dose of simva can't, like decrease CRP and prevent the progression of atherosclerosis. Currently, insurance companies push doctors and patients to use generics as seen by an 11% drop in Pfizer's blockbuster. Comparative effectiveness research might ask the question "in which patients should we be using Lipitor over generic simvastatin." This more rationale approach might actually help the branded product makers. This issue will be moot soon when Lipitor goes generic in 2010, but would be very important for Crestor at #11. Plavix would be another winner as more research has shown its benefit. Another winner might be Advair who has seen some decline in sales, most likely due to unnecessary safety fears. Study after study (including Cochrane reviews) show LABA/ICS to be the most effective treatment for asthma. This is important, as most asthmatics studied do not achieve good control.

However, there will also be some clear losers. Singulair would be one of them. This pill is considered alternative treatment by current asthma guidelines because it barely works. Yet, it beats Advair in number of prescriptions! The antidepressants and PPI's would also likely lose because study after study shows similar efficacy. The last on the top 10 list, Diovan, is of great interest to me. Cozaar will soon go generic, but it is the weakest of all the ARB's. Of the few head to head studies available, they all show the newer ARB's better than Cozaar. Currently, I never prescribe Cozaar for my patients that need ARB's (there are a few) because Diovan, Benicar, etc.don't cost them any more than Cozaar, and are clearly more effective. Comparative effectiveness might be a win for ARB companies other than Merk if evidence shows (as I suspect it would based on data and my experience) that it is probably worth it to pay a little extra for the other ARBs until they go generic.
Comparative effectiveness will also force the industry to focus on drugs that really add value as opposed to patent extenders. Novel new products that showed benefit would get comparative effectiveness' stamp of approval and would be theoretically covered despite a high cost.
In my addendum to this post, the Wall Street Journal clearly missed the boat. Medicines like the TZD's are costly, and though they don't seem to prevent heart attacks, the prevent hyopglycemia and more importantly can decrease the need for insulin (which is also very costly in many ways). There are other new diabetes products (saxaglipitn, lirglutide) that showed great promise at this week's ADA meeting. Yes, they are expensive, but similar to BARI 2D, comparative effectiveness would probably show that they are worth it.