4.1 Laboratories conducting routine testing have a continuing need to make improvements in their testing processes. In these situations it must be demonstrated that any changes will not cause an undesirable shift in the test results from the current testing process nor substantially affect a performance characteristic of the test method. This standard provides guidance on experiments and statistical methods needed to demonstrate that the test results from a modified testing process are equivalent to those from the current testing process, where equivalence is defined as agreement within a prescribed limit, termed an equivalence limit.

4.1.1 Examples of modifications to the testing process include, but are not limited, to the following:

(1) Changes to operating levels in the steps of the test method procedure,

(2) Installation of new instruments, apparatus, or sources of reagents and test materials,

(3) Evaluation of new personnel performing the testing, and

(4) Transfer of testing to a new location.

4.1.2 The equivalence limit, which represents a worst-case difference, is determined prior to the equivalence test and its value is usually set by consensus among subject-matter experts.

4.2 Two principal types of equivalence are covered in the practice, means equivalence and non-inferiority. Means equivalence implies that a sustained shift in test results between the modified and current testing processes refers to an absolute difference, meaning differences in either direction from zero. Non-inferiority is concerned with a difference only in the direction of an inferior outcome in a performance characteristic of the modified testing procedure versus the current testing procedure.

4.2.1 Equivalence testing is performed by an experiment that generates test results from the modified and current testing procedures on the same materials that are routinely tested. An exception is bias equivalence where the experiment consists of conducting multiple testing on a certified reference material (CRM) having an accepted reference value (ARV) to evaluate the test method bias.

4.2.2 Examples of performance characteristics directly applicable to the test method are bias, precision, sensitivity, specificity, linearity, and range. Additional characteristics are test cost and elapsed time to conduct the test procedure.

4.2.3 Non-inferiority may involve trade-offs in performance characteristics between the modified and current procedures. For example, the modified process may be slightly inferior to the established process with respect to assay sensitivity or precision but may have off-setting advantages such as faster delivery of results or lower testing costs.

4.3 Risk Management-Guidance is also provided for determining the amount of data required to control the risks of making the wrong decision in accepting or rejecting equivalence (see Section X1.2).

4.3.1 The consumer's risk is the risk of falsely declaring equivalence. The probability associated with this risk is directly controlled to a low level so that accepting equivalence gives a high degree of assurance that the true difference is less than the equivalence limit.

4.3.2 The producer's risk is the risk of falsely rejecting equivalence. The probability associated with this risk is controlled by the amount of data generated by the experiment. If valid improvements are rejected by equivalence testing, this can lead to opportunity losses to the company and its laboratories (the producers) or cause unnecessary additional effort in improving the testing process.