Conflict Between Guideline Methodologic Quality and Recommendation Validity: A Potential Problem for Practitioners (Evidence-Based Laboratory Medicine and Test Utilization‪)‬

The methodologic quality of current practice guidelines must be improved (1-20). For many reasons, the methodologic quality of diagnostic guidelines is poorer than that of therapeutic guidelines, particularly in the field of laboratory medicine (10, 21, 22). It is not clear, however, whether these shortcomings in the methodology of guideline development necessarily lead to invalid recommendations, i.e., those that are not supported with consistent research evidence or sufficient consensus among the guideline development team when evidence is conflicting or lacking. We assessed to what extent methodologic quality is linked to recommendation validity in practice guidelines for the use of laboratory tests in the management of patients with non-small cell lung cancer (NSCLC), [7] specifically laboratory tests measuring quantities in biological specimens, thus excluding tissue (or anatomic) pathology tests. Surgery performed at the early stages of NSCLC (I, II, or IIIA to a lesser extent) offers patients a reasonable chance of long-term survival, but this option is available to only a small minority of patients. In more advanced NSCLC (IIIB or higher), chemotherapy alone and chemotherapy with radiotherapy are options, but these therapies mostly aim to prolong patient survival, and the over-whelming majority of patients relapse. In many treatment facilities, no standard therapeutic schemes exist; therefore, controlled trials that include as many patients as possible are needed to assess the potential contribution of new drugs and new therapeutic schemes (23-26). Demonstrating the superiority of a given protocol over another is difficult to accomplish if the prognostic features of different patient subgroups cannot be compared. Consequently, independent prognostic factors must be identified before valid therapeutic trials can be designed, conducted, and interpreted (27). The medical and scientific communities have developed methods for conducting and reporting such therapeutic trials (28).