Foreshadowed by the College of American Pathologists revised predictive marker guidelines such as for Her 2 testing, is an industry trend of increasing validation requirements and practice standardization. If you have been working in the histology industry for a while, you are not surprised by this, since each year the accreditation checklists grow and more documentation is needed to remain compliant. My own feeling has been that when the 2007 ASCO/CAP Her 2 testing guidelines were established, that this was a trend in-the making. Most people thought at that time that my feeling that everything was moving towards the Her 2 standard, was a pretty far-fetched idea. But while I never believed, even at that time that all IHC testing would have such specific and formal guidelines as Her 2, I did think more & more testing would eventually have both practice guidelines and specific standards reminiscent of the template established by the Her 2 guidelines.
Some possible gray areas to be detailed within new guidelines
- Non predictive IHC assays, such as cell markers (keratins, actin etc.) – How many cases are needed in validation study?
- Will all testing need correlation with another laboratory or validated method?
- What is the acceptable level of concordance for many other assays types?
- Are there situations where verification is acceptable and validation is not necessary?
In support of my premise that there is noticeable movement to increasing validation-consider the recent appearance of the front page of the current issue of CAP TODAY of the College of American Pathologists survey results of the IHC validation practices of 727 laboratories in the article “Immunohistochemistry Validation Procedures and Practices “ ( CAP today, Vol. 28, No.3, 2014) . I propose that publications like these act as “heads up” notices to what possible expectations are on the horizon for validation and everything else , and which will appear as requirements in future guidelines and accreditation checklists. When you see an article like this, this is your chance, to have a bit more time to prepare for what you will be expected to do down the road. The data revealed in this IHC validation study didn’t show much that I thought was completely unexpected, (see some data compiled from the survey in the table below).
|Survey Results for Validation Practices with Non-Predictive IHC- FDA Approved|
|Lab has written validation SOP||68%|
|SOP defines # cases for validation||53%|
|SOP defines new antibody lot testing||56%*|
Basically to summarize what I gathered from this article is that that generally laboratories are making good faith attempts to meet validation standards for immunohistochemical assays, but there are some gaps and disparities from lab to lab. I think what is important about these types of publications is of course that they gather national data for comparisons, but also that they provide data which help highlight for CAP and other agencies charged with monitoring quality and patient safety – areas of concern and attention with regards to patient safety and quality improvement. So basically, wherever there are these identified gaps and areas of concern, expect these same areas to be addressed in some guideline very soon. ( i.e. pending CAP guideline- Immunohistochemical Assay Analytic Validation Principles, currently in review and approve status- as an example of how this kind data for IHC has spawned revised guidelines and eventually checklist requirements-and why I want to call you attention to the “heads – up” factor on expecting more stringent validation expectations across the checklists).
Please also consider the CAP guidelines listed in the table below as additional examples of how I think this develops. Most of the guideline topics were practices which in the past were activities which were only loosely directed, and now they have become part of a formalized practice guideline. My belief is that at least all immunohistochemistry markers, any semi-quantitative testing methods, and many other types of processes such as preanaltyic handling/fixation, patient identification, validation and reporting will be defined by diagnostic algorithms, practice standards and guidelines with diagnostically defined report formatting much like Her 2 and other predictive markers. (also consider the CAP sponsored guideline, CAP-NSH collaborative Uniform Labeling guideline, CAP required synoptic report formatting for tumor-biomarkers, expanding HQIP catalog of tissue specific-diagnostic specific challenges, increasing required and optimal CAP proficiency challenges). Take home is, maybe not everything will become as defined as Her 2, but nearly everything is likely to become much more defined than it currently is.
I believe that all of these guidelines listed in the table below have started out as studies, surveys or publications, which were later consolidated into practice recommendations, and eventually become incorporated into formal guidelines and accreditation checklist items.
|Current CAP Guidelines||Some Upcoming Guidelines|
|Principles of Analytic Validation of Immunohistochemical Assays||Immunohistochemical Assay Analytic Validation Principles|
|Guideline Recommendations for Her 2 Testing in Breast Cancer||CAP/ASH Algorithm for Initial Work-up of Acute Leukemia|
|Validation of Whole Slide Imaging for Diagnostic Purposes in Pathology||CAP-NSH Uniform Labeling Requirements for Blocks and Slides in Surgical Pathology|
|Consensus Statement of Effective Communication of Urgent Diagnoses and Significant Unexpected Diagnoses in Surgical Pathology and Cytopathology||Her 2 Testing in Gastric Cancer|
|Guideline for Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer|
To view the complete CAP guideline publications from their website as summary pages or PDF files, clink on the hyperlink GUIDELINES here.
A few notable conclusions can be taken away from even a quick review of these guidelines
- There is an obvious push to increase uniformity and standardization of practices across individual laboratories.
- The mindset presented is one of movement toward evidence-based medical practices; especially those practices demonstrated to improve diagnostic and patient treatment decision- making and reduce cost and waste.
- The standard of practices in any individual laboratory will increasingly be expected to follow standardized methodology and be capable of high correlation with similar results and data from other laboratories.
- It will become imperative for data collection to be in a uniform and standardized syntax to allow more accessibility for data mining, collaborative data sharing and information exchange via shared interfacing and central databases.
Perhaps I have made a convincing introductory argument concerning how we have moved forward from some of our hazy and ill-defined standards of the past to one of ever increasing standardization. I would suggest that the next time you see one of these initial publications you begin at that moment considering how you are going to meet the challenges it presents, and decide how you will incorporate the changes it proposes- well before you really have to. All of us struggle at times to adapt to change and rise to new challenges, (it seems we always have less resources, increasing workloads, ever-diminishing staff…) yet as a group, we always carry on. Usually, after not too much time has passed, we realize that most of the changes will end up being positive and worthwhile.
Joelle Weaver MAOM, HTL (ASCP), QIHC
College of American Pathologists. Current Guidelines. Retrieved 4/15/2014 from http://www.cap.org
Hardy, L. Fitzgibbons, P. et al. Immunohistochemistry Validation Procedures and Practices, a College of American Pathologists Survey of 727 Laboratories. Archives of Pathology & Laboratory Medicine, January 2013.
Morken, T and Ruegg, P. Validation and Quality Control for Immunohistochemistry. NSH Symposium, Seattle, Washington. September, 2010.
Wolff, A. et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Archive of Pathology & Laboratory Medicine. ASCO/CAP HER2 testing Guideline Update. June, 2013.
*Data from Hardy et al., Immunohistochemistry Validation Procedures & Practices, CAP survey of 727 Laboratories, 2013.