Enrollment bias and variation in clinical manifestations: a review of consecutive cases of familial paroxysmal polyserositis.

The effect of systematic enrollment bias was studied in a series of 158 patients with familial paroxysmal polyserositis (F.P.P.) from a special clinic in a university hospital. The characteristics of 79 patients seen for the first time at this special clinic in its first 16 months of operation, were compared with the characteristics of 79 patients presented during the last 6 yr of its operation. As a group the patients studied first at the clinic had a more severe form of the disease. This group had a significantly larger number of patients with multiple clinical manifestations, with proteinuria and amyloidosis. In addition, there were more males and more patients with positive family history of the disease in this earlier group. It is probable that much of the temporal variation in these clinical characteristics between patients studied in the earlier and later periods can be explained by case selection originating from differentials in referral patterns. Thus, a larger proportion of the earlier patients were referred following an episode of hospitalization. Differences in referral pattern, in case selection and in the sources of data, can account for the significant variation in the frequency of the various clinical manifestations in the different published F.P.P. case series from several countries. The effect of enrollment bias on the results of clinical studies and the importance of a population base for such studies is emphasized.