[gdpawel]

The method used to present information about chemotherapy influences treatment decisions. In deciding on endorsing chemotherapy, patients understand the information best when presented with data in the absolute survival benefit format, rather than those presented with data in the relative risk reduction information format. Absolute survival benefit is the most easily understood method of conveying the information regarding benefit of treatment.

Discussions between doctors and patients about the risks and benefits of chemotherapy need to be changed. Being told that chemotherapy reduces your risk by 30% of recurrence can be misleading and meaningless, unless you know your risk in the first place. If your risk of recurrence is 15%, you are only reducing it by 5%. And this doesn't even reflect the harm that could be done to those who don't need the treatment.

What is that harm? There are the toxicities that can end your life: leukemia and heart failure. There are toxicities that can ruin your life: loss of libido, loss of cognitive function, severe joint pain, and bone fractures. These harms are usually ignored or understated. One of the reasons is because they are understudied.

How will gene profiling for prognosis and prediction be used in the real world? Will women choose chemotherapy even though they have only a small chance of a recurrence? The bias towards chemotherapy and its overuse still permeates our society and will affect how this profile test is used. Many women will opt for chemotherapy even for a one or two percent benefit. Will women consider a low risk result low enough to forgo chemotherapy, or will they persue it anyway because of historic bias?

I've always known about the pervasive way clinical trials focus on the relative risk (which powerfully exaggerates the benefits of drugs) and drug companies frame the question in terms of relative risks (systematically inflates their value), and absolute risk.

The number needed to treat (NNT), developed in 1988 to avoid the confusing distinction between "relative" and "absolute" reduction of risk, is perhaps one of the most important, least recognized, and most emblematic distortions you can find.

Some years back, the NCI issued a clinical alert to oncologists announcing the results of several clinical trials showing that women with node negative breast cancer benefited from chemotherapy. According to "number needed to treat" analysis, one hundred women would have to undergo chemotherapy for 10 to benefit.

Ninety women would risk toxicities but get none of the benefits. So what is the harm? The toxicities included not only those that can end your life like heart failure and leukemia, but some of those that can ruin you life like loss of cognitive function, loss of libido, severe arthritis and risk of bone fractures. These harms are usually ignored or understated. One of the reasons is because they are understudied.

So it began the "standard" practice to administer chemotherapy to women with node negative breast cancer that still exists today. Treat everyone to improve the survival chances of a small minority. How will the new gene profiling tests for prognosis be used in the real world today? Will women choose chemotherapy even though they have only a small chance of a recurrence? The bias towards chemotherapy and its overuse still permeates our society and will affect how these profile tests are used.

Many women will opt for chemotherapy even for a one or two percent benefit. Will women consider a low risk result low enought to forgo chemotherapy, or will they persue it anyway because of historic bias?

The clinical alert mentioned above was issued in 1987, a year before the NNT was developed to avoid the confusing distinction between "relative" and "absolute" reduction of risk.

A more honest use of NNT is not just an issue of forthrightness, it is also cost-effective.