Levels of evaluation of preimplantation testing of human embryos

Screening, diagnostic, and prognostic tests can be essential tools enabling healthcare professionals and patients to make informed decisions. A test of a human embryo can assess markers of morbid or lethal conditions, identifying embryos that may not be transferred back into a prospective parent. Alternatively, features identified in an early human embryo may be used to provide a prognosis of reproductive competence. We propose four levels of evaluation of tests of human embryos. Each has a unique methodology and specific clinical aspects. Phase 1 assesses analytic performance and validation to assess that the test consistently produces accurate, reliable, and reproducible results for its intended purpose. Phase 2 assesses clinical performance with diagnostic and predictive value studies. To obtain an unbiased assessment of test characteristics, embryos need to be transferred regardless of the test result. The predicted outcome is then compared with the actual outcome as the reference standard. Phase 3 is the assessment of clinical benefit, including the effectiveness or efficiency of the testing strategy's utilization. The design and conduct of a clinical trial must be tailored to the specific questions of interest and balance outcomes unique to reproductive medicine, including patient-centric outcomes. Phase 4 included the ongoing reporting of key performance indicators, quality assessments, and safety. Once a test is established and in clinical use, it should undergo transparent, rigorous monitoring and evaluation to ensure the reliability of results and patient safety. Optimally, a test should be demonstrated to have good characteristics in each stage of development before moving to the next one to enhance the likelihood of having positive results in the next phase and to efficiently use time, money, and ethics. Just as important, it will also optimize the likelihood that a test is clinically valuable. These levels of development can be applied to existing tests or the future development of tests.