Clinical and Laboratory Standards Institute EP46—Determining Allowable Total Error Goals and Limits for Quantitative Medical Laboratory Measurement Procedures provides developers (both commercial manufacturers and laboratories that create laboratory-developed tests) and medical laboratory end users with models to inform the determination of allowable total error (ATE) goals and limits. ATE goals and limits are useful during both the Establishment and Implementation Stages of the Test Life Phases Model (see CLSI EP19) to assist in determining acceptance criteria for Validation and Verification Phase performance evaluations. Approaches for determining ATE goals and limits are described based on the effect of analytical performance on clinical outcomes, the comparison with biological variation of the measurand, and the state of the art based on analytical performance similar to that of a peer group. Considerations to the phases of a measurement procedure (preanalytical, analytical, and postanalytical) in setting ATE goals or limits and sources of error contributing to the estimate of total error for which ATE is to be determined are also described. CLSI EP46 is a resource for many CLSI method evaluation documents. Before performing a study to estimate an analytical performance characteristic of a quantitative measurement procedure (accuracy, precision, linearity, etc.), acceptance criteria should be set. These acceptance criteria should be linked to the ATE goals or limits for the measurand. CLSI EP46 provides approaches for determining ATE goals or limits and describes their application. CLSI EP46 can be used to set the ATE limits for the study protocol presented in CLSI EP21 for determining the total analytical error for a quantitative measurement procedure.

CLSI EP46 provides guidance for selecting the relevant sources for establishing allowable total error (ATE) goals and/or limits for quantitative medical laboratory measurement procedures. This guidance is suitable for both commercial products as well as laboratory-developed tests (LDTs). It is particularly useful for end-user medical laboratories to set acceptance criteria (ie, limits) for total analytical error (TAE) before performing studies described in CLSI EP21 and can be used to determine acceptability of a measurement procedure for use to inform clinical decisions. 

The intended users of CLSI EP46 are developers of measurement procedures (both commercial manufacturers and laboratories that create LDTs), regulatory authorities, and medical laboratory personnel. 

Users should learn how to: 
• Describe error and classifications of error as preanalytical, analytical, or postanalytical; random or systematic. 
• Compare frameworks for applying total error concepts. 
• Consider the multiple sources of error contributing to bias and imprecision in a measurement procedure. 
• Determine ATE limits using models based on clinical outcome studies, biological variation of the measurand, and/or the state of the art of the measurand, dependent on the availability of data. 

CLSI EP46 is not intended to provide recommendations or endorsement for specific sources of ATE limits. It does not provide guidance on estimating and evaluating TAE for quantitative measurement procedures, but instead directs users to CLSI EP21 for information on this topic.