This analysis indicates that hierarchical case definitions of increasing sophistication, involving confirmatory physical signs, more specific symptom patterns, or additional investigations, yield remarkably similar associations with putative occupational risk factors to those obtained using simpler case definitions.
Our analysis has certain limitations. In particular, the search strategy is unlikely to have discovered every occupational report over the two decades of inquiry that involved multiple case definitions. Specifying sensitive electronic search terms for this topic is challenging. To make the task manageable, we focussed on systematic reviews of occupational risk factors at each anatomical site as our main source of references to primary research reports, but to improve the detection rate we also hand-searched five leading peer-reviewed occupational journals. In the event, hand-searching identified only three potentially eligible papers missed by the database screen, lending some validity to our search. More importantly, papers were selected blind to information on the ratios of interest, and we have no reason to suppose that the reports retrieved were unrepresentative of the universe of relevant studies in the peer-reviewed literature.
A second area of difficulty lies in evaluating the role of chance in the ratio measures obtained. Scope to estimate CIs for the ratios was limited by the nested nature of many observations and the indeterminate extent of overlap in others. However, the infrequency of ratios of >2 across all 320 comparisons, and of lower confidence limits of RRs for stricter definitions exceeding the central estimates for simpler definitions, argue against important differences being overlooked by chance. Additionally, findings were insensitive to the exclusion of two large influential studies that contributed more than half the observations, suggesting that this possible non-independence of data points from the same study was not a cause of material bias. A further sensitivity analysis suggested that the potential for bias arising from differences in the reference group for paired risk estimates was inconsequential.
A lack of detectable difference between case definitions (ratio close to unity) could arise if the occupational exposures studied were not risk factors for symptoms or disorders at the sites in question, or were defined with substantial measurement error, such as to appear so. However, many of the exposures evaluated were well established or plausible risk factors, and RRs exceeded 1.0 for 81% of the 640 estimates of RR identified during the review. True differences might also be masked by confounding. However, estimates were adjusted in the same statistical models and any superiority in favour of the stricter definition could only be masked by systematic negative confounding relative to the simpler definition. Differences in approach to exposure assessment between studies are unlikely to have biased findings, given the focus on ratios of RRs derived within-study comparisons in which exposures were defined identically.
Alternatively, and more plausibly, little “added value” is created by case definitions of increasing sophistication relative to simple ones in population-level studies, and if so a good case exists for simplification. In planning field studies of ULDs and occupational risk factors, or employers’ surveys of hazard and risk, resource expended on additional physical examinations or investigations will generally yield marginal or no benefits; whereas costs will be predictably higher, with added problems of inconvenience and non-compliance. Similarly, in health surveillance, a complex case definition will be more difficult to implement uniformly across settings and over time, with no clear offsetting benefits.
Our findings do not identify a preferred set of case definitions for ULDs in the context of prevention and surveillance at the population level. Rather, they suggest that variations make little difference. Thus, the preferred starting point for aetiological investigation will normally be a broad case definition that is simpler to apply and may give more cases and therefore greater statistical power. This does not preclude additional exploratory analyses on subsets of cases defined according to more stringent diagnostic criteria, if researchers wish to seek evidence of differential associations with risk factors. It may also be more efficient to use stricter criteria when cases have already been defined in this way (for example, if cases of CTS are readily identifiable from the records of a neurophysiology department, all of whom meet certain criteria following nerve conduction testing). In most situations, however, simple case definitions will suffice. Similarly, in surveillance, simple choices which are easier to implement will usually be preferable.
Finally, in appraising the research literature, our findings imply that heterogeneity of case mix and variations in approach to case classification have less impact than might be supposed. This gives a justification in systematic reviews and meta-analyses for pooling data on associations with risk factors at a given anatomical site between studies, even though such studies may have differences of case definition.
More generally, the utilitarian framework offers an empirical basis for moving towards a simpler, more rational basis on which to classify ULDs for preventive purposes.