October 11, 2012
I recently mentioned that I have published a blog entry in a journal. The current entry is the reverse, where this blog entry is based on a recent publication (Krouwer, JS Interference Testing: Why Following Standards Is Not Always the Right Thing to Do. Journal of Diabetes Science and Technology, 2012;6:1182–1184.)
In this publication, I note that the CLSI standard about interference testing – EP7-A2 – recommends that a manufacturer may state that there was no interference if a substance meets a clinical goal where the level of bias from interference will not cause clinical harm. For example, if for substance “A” the clinical goal is bias from interference less than 10%, the manufacturer could state substance “A” does not interfere, even if it were true that substance “A” caused a bias of 9%.
This is wrong because it mixes the concept of finding an analytical interference (call this bias level 1) and the level of interference required to cause harm (call this bias level 2.) Laboratorians would like to know both concentration levels. So a table of interfering substances should look like this.
Substances that fail would have more information.
The reason for this blog entry is that I just got a copy of CLSI C56-A, which is about interference testing for hemolysis, icterus, and lipemia and for this manufacturing dominated standards group, C56-A has the same problem as EP7-A2.
October 9, 2012
Ioannidis has written an interesting article (1) about biomarker failures, but I don’t agree with his first example of a failure. He says that PSA is a failure and “largely useless— or even harmful—and therefore needs to be abandoned.” He offers as evidence the recent USPSTF recommendation, which recommends against PSA screening altogether (2).
But there are several reasons to question abandoning PSA. For one, the USPSTF data analysis has been challenged (3). Secondly, an update (4) from the ERSPC Trial showed that PSA screening does significantly reduce death from prostate cancer whereby a man who undergoes PSA testing will have his risk of dying from prostate cancer reduced by 29%. And thirdly, one can question whether cost played a role in the USPSTF conclusion. The USPSTF is empowered by the Affordable Care Act. Ezekiel Emmanuel, President Obama’s special health care advisor suggested (5) that “the complete lives system produces a priority curve on which individuals aged between roughly 15 and 40 years get the most substantial chance [of healthcare resources], whereas the youngest and oldest people get chances that are attenuated.” PSA screening has been recommended to start at age 50.
There would be considerable cost savings for:
- the population of men over 50 in the US (or between 50 and 75) that would no longer receive a PSA test
- the number of men that would have had an elevated PSA that would not receive a biopsy
- the number men that would have been diagnosed with early prostate cancer via a PSA test / biopsy (~ 200,000 per year) that would not receive treatment (surgery or radiation)
So in spite of the fact that PSA has many false positives (and some false negatives) and that there is overtreatment of prostate cancer, just because an expert panel concluded to abandon PSA, this does not mean it is the right conclusion.
- Ioannidis JP, Biomarker Failures Clin Chem 59 in press.
- Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:120–34.
- Schröder, FH, Stratifying Risk — The U.S. Preventive Services Task Force and Prostate-Cancer Screening N Engl J Med 2011; 365:1953-1955.
- Schröder, FH, Hugosson, J, Roobol, MJ, et. al. Prostate-Cancer Mortality at 11 Years of Follow-up N Engl J Med 2012;366:981-90.
- Persad G, Wertheimer A, Emanuel EJ, Principles for allocation of scarce medical interventions. Lancet 2009; 373: 423–31.
October 8, 2012
A while ago I edited one of my blog entries and sent it in as a Letter to the Editor to Clinical Chemistry. Much to my surprise it was published: Krouwer JS, Wrong thinking about glucose standards. Clin Chem, 2010;56:874-875.
I edited my last blog entry and sent it in as a Letter to the Editor. But when I read the instructions for authors, I noted that it said that letters would only be accepted for articles or brief communications and sure enough my letter was rejected by not being about an article or brief communication. Apparently, the policy has changed because my previous letter was about a Q&A piece: Sacks DB. Tight glucose control in critically ill patients: Should glucose meters be used?. Clin Chem 2009;55:1580-1583.
So this made me think how much of Clinical Chemistry is comprised of articles or brief communications. The results are:
Percent that is not
articles or brief communications
This seems messed up. Almost half of what is in Clinical Chemistry is not subject to comment.
I will publish my edited blog entry shortly.