Tag: validation

Validate, Transfer or Establish: What Are You Doing with Your Reference Intervals?

Reference intervals are absolutely necessary for proper interpretation of laboratory tests, and yet obtaining appropriate reference intervals can be the bane of the laboratory. I mentioned establishing, validating or transferring reference intervals in an earlier blog post, but didn’t talk about exactly what these are and when to use which one.

Establishing a reference interval is exactly what it says. A reference interval must be established if a new assay has never been performed in the lab and there is no current reference interval to start with. Most often, laboratory developed tests (LDTs) that are developed from scratch will require the establishment of a reference interval. To do this, ideally 120 samples from healthy individuals for each sub-population (gender or age sub-group) is used, although there are methods available using smaller sample sizes. Samples used to establish reference intervals may be collected a priori, meaning they are collected from individuals for the express purpose of establishing a reference interval, with well-defined inclusion or exclusion criteria used, or a posteriori, meaning they are samples collected and analyzed first, with exclusion criteria applied after statistical analysis.

Validating a reference interval is the easiest way to obtain one, and is what is hoped for when a new method is introduced. Validation is usually used when a new instrument or method replaces an old one, and reference intervals are currently in place. A patient correlation study is done using at least 20 patients. The data is analyzed with regression, bias and correlation statistics. If the bias and regression are acceptable, the reference interval that is currently in place will also work with the new assay. The interval has been validated and can be used with the new method.

When a validation study is done for a new method and the results of the data analysis are NOT acceptable to validate the assay, then a transference study is necessary. A transference study is simply an extended correlation. More than 20 patients are used, enough to determine the amount of bias between the two methods. Then the old reference interval is adapted to fit the new method, using the amount of bias determined. For example if the new method measures 15 percent higher than the old method, the reference intervals will be increased 15 percent across the board. Transference is recommended to be performed once. If another new method is brought in for that analyte, rather than transfer the reference interval again, a new interval should be established.

All three of these methods for obtaining reference intervals are useful in the right situations. It is important to know when to use which method.

 

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-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

Simplify Equipment Validation with a Validation Master Plan

How compliant are you with all your clinical equipment validation (including the point of care equipment)? The equipment validation process is a crucial component in any clinical laboratory practice; any serious deficiency in equipment validation could threaten the business continuance of the institution. Clinical Laboratory Improvement Amendments (CLIA) regulations set standards on test systems, equipment, instruments, reagents, materials, and supplies for clinical laboratories. Laboratories must properly qualify, monitor, and verify or establish performance specifications for any test systems used for patient testing. The federal regulations and explanation for Verification of Performance Specification and Calibration and Calibration Verifications (as well as other CLIA regulations) can be found on the CMS website.

New equipment comes to the laboratory with settings already in place by the manufacturer. For example, urine drug screen analytes may be preset at certain cutoff levels. It is the laboratory’s responsibility to recheck all new equipment validation on all the so called “manufacturer settings.” A detailed guidance document on equipment validation was published by the Clinical and Laboratory Standards Institute (CLSI) in August 2011. QMS13A (formerly GP37A Equipment Validation) outlines the equipment validation process into several crucial validation components: Selection Qualification (SQ), Installation Qualification (IQ), Operational Qualification, and Performance Qualification (PQ).

Laboratories should start a strategic and simple approach to equipment validation with a validation master plan (VMP). This plan provides a structured approach to equipment validation that will allow many problems to be addressed before they become crises. It also assures equipment needs (functional, business and technical) are met. A VMP should:

  • Be approved by the laboratory’s medical director.
  • Appropriately assess and mitigate any potential hazards.
  • Establish policies and procedures.
  • Assign equipment data reviews.
  • Include personnel training for all shifts.
  • Comply with all patient safety requirements.
  • Outline the timeframe from equipment acquisition to “go live” date.
  • Include accuracy and precision studies.
  • Specify the reportable range and normal values for all analytes.

Typically, 20 samples for each level of normal and abnormal results should be tested for accuracy and precision studies. Clinical equipment should never be used for patient testing until all validation processes reviewed, assessed and approved by the appropriate medical lab director. When determining the reportable range, calibrators and samples should reflect the full range. For example, if the manufacturer suggests a reportable range for glucose of 10 mg/dl to 600 mg/dl, having the lowest sample test at 50 mg/dl would be unacceptable.

In summary, creating and designing a good VMP can save all the agonies and time spent in later future in equipment validation in any clinical laboratory or point of care department. Once one successful VMP have been accomplished and produced, future equipment validation would become much easier and manageable. The overall process would ultimately assure accuracy and reliability of the equipment system in the institution, thereby improving patient safety.

 

Information on policies or practices are solely from my personal experience ONLY and have NO relation to my affiliation with any regulatory or government agency.

 satyadi

-Caroline Satyadi, MT(ASCP), SM, DLM, SLS, MBA, MS, CQA (ASQ) has been a laboratory management professional for over 25 years. She has worked with several different medical industries for CLIA/CMS, FDA/ICH/ISO, TJC/CAP/COLA/HFAP accreditation survey readiness.