I am happy to respond to Dr. Rich’s blog entry which refers to me. I enjoy reading Dr. Rich’s blog, value his wisdom, and thoroughly enjoyed his book. I agree with Dr. Rich that
“the controversy regarding CER has to do with how its results will be applied”
“DrRich suspects that Dr. Krouwer is more familiar with laboratory research than with clinical research”
Actually, what I do is analyze data. It usually does relate to the laboratory via diagnostic companies.
Dr. Rich talks about the problems with randomized clinical trials (RCT). I agree with his points; however, take different treatments for prostate cancer. Here, a RCT make no sense because the study would be too complicated, expensive, and take too long with respect to a viable alternative.
There are at least 8 treatments for prostate cancer:
- Active surveillance (watchful waiting)
- Open radical prostatectomy
- Laparoscopic radical prostatectomy
- IMRT radiation
- Proton beam therapy
- Brachytherapy (seeds)
- HIFU (not approved in the US)
However, the number of categories increases because:
Patients are usually subdivided into low, intermediate , or high risk as a function of PSA, Gleason score, and stage. This leads to 24 treatment categories. Moreover, there are a variety of other complicating factors such as combination treatments including the use of androgen derivation therapy (ADT) applied to some patients for one of several reasons, surgical skill for relevant procedures, localized therapy, salvage treatments, and so on.
The alternative to a RCT is simply to analyze existing data. There are around 185,000 men diagnosed with prostate cancer each year. Each ten years provides 1,850,000 cases. That’s a lot of data! If one had a way of simply collecting the outcomes (success rates, side effects, total cost) of each case, one would have CER.
Yet, existing studies that attempt to answer some of these questions have bias. To deal with all points would be a book so take one example – incontinence as a side effect of treatment, especially radical prostatectomy.
First, one has to take into account the pre treatment rate of incontinence which is around 9% – see WebMD (the pre treatment rate is a bigger issue for another side effect – erectile dysfunction). It is not clear that studies take into account prior side effect rates.
From Medscape, physician-reported studies report a lower rate of incontinence than when patients are surveyed. One can speculate that physicians would like to minimize the side effects of treatments that they provide. Moreover, the definition of incontinence including when it is measured after treatment differs among studies or is not provided at all. And of course, some of the definitions are questionable. Thus, using less than three pads a day qualifies as continent according to Zincke, et. al.
What is needed is standardization of terms and survey instruments and a reliable method to collect this data. If this doesn’t occur, then it will be hard to draw conclusions about this side effect whether the study is transparent (well described) or not. One can argue that there will always be some bias but it does matter how much if policies will result from such studies.