Monday, January 1, 2007

Not quite a repost - Number Needed to Treat (NNT)

Rather than repost this entry on the NNT, I thought I would discuss the issue a little further. For background, here are some references:
For the individual, the NNT doesn't really matter. After all, when you take a drug, it doesn't matter what happens to other people on the drug. It only matters what happens to you. However, for public policy makers and insurance companies, the NNT has become very important. The reasoning goes as follows:

Say you, as an insurance company, wanted to compare two therapies to prevent serious cardiovascular events (e.g. cardiovascular death, myocardial infarction): niacin and simvastatin. The cost of a cardiac event is high both economically (in terms of health care cost and days missed) and in pain and suffering. Then we can answer the following question: what is the cost of preventing one event using niacin and simvastatin?

You can organize the work as follows:
Therapy Source Duration (years) Cost/Day NNT Total Cost/1 prevention
Niacin Coronary Drug Project 6.2 $0.21 20 $9,511.11
Simvastatin 4S 5.4 $0.93 13 $23,845.71

The only calculated column is the last one (you can easily set this kind of table up in any spreadsheet). The calculation is total=duration*365.25*cost/day*NNT. In addition, I used a favorable cost for simvastatin (although it will get more favorable when more generics hit the market) and an unfavorable cost for niacin. Source of data is Tables 1 and 2 from Therapeutics Letter, May 1998 as shown here. Note that cerivastatin has been withdrawn since then, and a generic form of simvastatin has hit the market.

You can interpret the last column as follows: to prevent one cardiovascular event, you expect to pay $9,511.11 for niacin therapy or $23,845.71 for simvastatin therapy.

Simvastatin actually doesn't compare too unfavorably with niacin therapy. Other measures such as safety profile (including NNH - Number Needed to Harm - for the more serious adverse events) are needed in the decision making process, but under this measure we should not rule out simvastatin as a valid and effective therapy. The main issue is unit cost, something that will change as generics come on the market or something that can be negotiated down (especially in the case of transporting drugs to developing countries).

Speaking of safety profile, that is something that hasn't been figured into the table above. The costs associated with flushing, gastrointestinal problems, skin problems, and acute gout, -- all associated with niacin -- along with the NNH for these issues, need to be addressed. On the simvastatin side, creatine kinase elevation with muscle weakness and rhabdomyolysis need to be addressed, along with the other adverse events that have been found to be associated to statin therapy in the last couple of years. These expected costs are to be added to the costs in the table above.

There are a few caveats to the NNT a couple of which I mention below:
  • First, the NNT is a number derived from an estimate, i.e. 1/absolute risk reduction. Though most estimates are reported with a standard error, NNTs are not (and this is a flaw). Likewise, the costs above have a range deriving from several sources: range of cost, range of NNT, range of durations studied.
  • The NNT is based on population-based statistics. For an individual making an individual decision about healthcare, it carries less weight than it would for an insurance company deciding which therapies to cover or a healthcare NGO deciding which therapies to pay for transport into developing countries. Side effect risk factors, metabolism profile, and other individual factors carry more weight (and those carry less, but higher than zero, weight with policy makers).
So next on my plate in the NNT series is how to compute a standard error from measures that you see in the literature.