Two-way referral bias: Evidence from a clinical audit of lymphoma in a teaching hospital

The objective of this study was to evaluate the effect of referral bias in a clinical audit of lymphoma in a university hospital. We compared demographic and clinical characteristics as well as survival for Jerusalem residents (local) and referred (distant) patients diagnosed from 1987 to 1992 and treated in our institution. Referred patients were younger (P < 0.0001), and less likely to be immigrants (P < 0.0001), than local patients. Aggressive non-Hodgkin's lymphomas (NHL) were more common in the referred population (p = 0.015). Survival for Hodgkin's disease was consistently better for local patients, but for patients with NHL the findings were reversed. In this study referred patients differed in their clinical and sociodemographic characteristics but did not consistently exhibit a worse outcome than that of local patients. The unpredictable nature of referral bias may be due to better functional status or resources among referred patients, or to selective referral for procedures such as bone marrow transplantation. While reports on the natural history of disease from tertiary institutions may be biased by referral patterns, the direction of the bias is not uniform.