Ioannidis is Wrong

September 29, 2012


For some time, I have been a follower of John P.A. Ioannidis, but I don’t agree with his recent analysis of PSA as a screening tool. 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. Of course, PSA does have false positive problems and overtreatment is an issue. But …

An update from the ERSPC Trial states that “The European Randomized Study of Screening for Prostate Cancer has published its 11-year follow-up results (New England Journal of Medicine, March 15 2012). Once again, they demonstrate that screening does significantly reduce death from prostate cancer. The latest study confirms that a man who undergoes PSA testing will have his risk of dying from prostate cancer reduced by 29%.”

And one can listen to an oncologist, who had metastatic prostate cancer and recovered, and now treats prostate cancer patients.

The USPSTF is empowered by the Affordable Care Act. It’s clear that healthcare spending by the government must be reduced. 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)

Isn’t it likely that cost had a role in the USPSTF decision? But this is not covered in the Ioannidis article.

EP27 – Inappropriate authorship in a CLSI Standard

September 28, 2012


The story

Early in 2007, I proposed a project for CLSI about error grids. The project was approved in early 2008 and I formed a subcommittee (now called document development committee). By the end of 2008 we had had seven teleconferences and produced a substantial draft. EP27-P (P=Proposed) was published in 2009. In 2010, EP27-A (A=Approved) was sent to the Board. There were a substantial number of comments mostly editorial and mainly from one unidentified Board member (later identified as Greg Miller) in August 2010. The comments were promptly addressed. The subcommittee then learned in April of 2011 that the Board had a new series of comments. But CLSI had sat on the document for six months. Comments were addressed again and the entire voting process was repeated with the document sent to the CLSI membership (again) in August 2011. In January, 2012, again after a six month delay, I was told the project had been cancelled and a new document development committee had been formed.

In August, 2012, a revised draft was sent to the CLSI membership. With one exception, the original people who worked on EP27 were dropped as authors, yet the material is largely the same.

Replacing the original list of authors with a new group is inappropriate and unprofessional

The revised version of EP27 has many parts of the original version lifted verbatim. Other parts are clearly identifiable as the original version but edited – note that it is always easier to edit than to create.

But the original document development committee was acknowledged

It doesn’t matter. From the website,

“You are allowed to borrow ideas or phrases from other sources provided you cite them properly and your usage is consistent with the guidelines set by fair use laws. As a rule, however, you should be careful about borrowing too liberally — if the case can be made that your work consists predominantly of someone else’s words or ideas, you may still be susceptible to charges of plagiarism. Also, if you follow the words of a source too closely, and do not use quotation marks, it can be considered plagiarism even if you cite the source.”

The new authors – listed below – will be credited in many ways for work done mostly by others. CLSI will acknowledge ‘their work’, they will be listed as authors in most citations of the document, and they can cite the document as a publication on their bios and resumes. Those who conceived and wrote the document cannot.

R. Neill Carey, PhD, FACB
Peninsula Regional Medical Center
Salisbury, Maryland, USA

Jacob B. Levine, MBA
Siemens Healthcare Diagnostics
Tarrytown, New York, USA

W. Gregory Miller, PhD
Virginia Commonwealth University
Richmond, Virginia, USA

Gene Pennello, PhD
FDA Center for Devices andRadiological Health
Silver Spring, Maryland, USA

Greg Miller is also the president of AACC and president elect of CLSI.

CLSI advertises itself as a “consensus” organization. But to change the document without consulting the original authors is not consensus.

Finally, the following is a list of previous articles about error grids that mention EP27-P.


  1. Krouwer JS. Why manufacturers should embrace error grids. IVD Technology 2010;16:18-21
  2. Krouwer JS and Cembrowski GS. A review of standards and statistics used to describe blood glucose monitor performance. Journal of Diabetes Science and Technology, 2010;4:75-83
  3. Krouwer JS. Wrong thinking about glucose standards. Clin Chem, 2010;56:874-875
  4. Krouwer JS and Cembrowski GS. Towards more complete specifications for acceptable analytical performance – a plea for error grid analysis. Clinical Chemistry and Laboratory Medicine, 2011;49:1127-1130

List of CLSI Standards

September 12, 2012

Previously, I had inadvertently not listed all of the CLSI standards for which I am an author. Here is the corrected list.

  1. Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition EP5-A2 NCCLS, 940 West Valley Road Suite 1400 Wayne, PA., 2004.
  2. Evaluation of the linearity of quantitative analytical methods; Approved Guideline – NCCLS EP6-A, NCCLS, 940 West Valley Road Suite 1400 Wayne, PA., 2003.
  3. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Second Edition EP9-A2 NCCLS, 940 West Valley Road Suite 1400 Wayne, PA., 2002.
  4. Preliminary Evaluation of Quantitative Clinical Chemistry Laboratory Methods; Approved Guideline NCCLS EP10-A3, NCCLS, 940 West Valley Road Suite 1400 Wayne, PA., 2006.
  5. Risk Management Techniques to Identify and Control Laboratory Error Sources; Approved Guideline—Second Edition EP18-A2, CLSI , 771 E. Lancaster Ave. Villanova, PA., 2009
  6. A Framework for NCCLS Evaluation Protocols; Proposed Guideline NCCLS EP19-R, July, 2002, NCCLS, 940 West Valley Road Suite 1400 Wayne, PA., 2002
  7. Estimation of Total Analytical Error for Clinical Laboratory Methods; Approved Guideline NCCLS EP21-A, NCCLS, 940 West Valley Road Suite 1400 Wayne, PA., 2003.
  8. How to Construct and Interpret an Error Grid for Diagnostic Assays. Proposed Guideline CLSI EP27-P, CLSI, 940 West Valley Road Suite 1400 Wayne, PA., 2009.