Impact of definitions of loss to follow-up on estimates of retention, disease progression, and mortality: application to an HIV program in Mozambique

Abstract

Patient retention is critical to the management of chronic diseases such as human immunodeficiency virus (HIV); hence, accurate measures of loss to follow-up (LTF) are important. Many different LTF definitions have been proposed. In a cohort of 9,692 HIV-infected patients initiating antiretroviral therapy in Mozambique from 2006 to 2011, we investigated the impact of the definition of LTF on estimated rates of LTF, acquired immunodeficiency syndrome (AIDS)-defining events, and death by applying 17 different definitions of LTF gleaned from HIV literature. We further investigated the impact of 4 specific components of the LTF definitions. Cumulative incidences of LTF and AIDS-defining events were estimated by treating death as a competing risk; Kaplan-Meier techniques and variations to account for informative censoring were used to estimate rates of mortality. Estimates of LTF 2 years after treatment initiation were high and varied substantially, from 22% to 84% depending on the LTF definition used. Estimates of 2-year mortality varied from 11% to 16%, and estimates of 2-year AIDS-defining events varied from 6% to 8%. As seen here, the choice of LTF definition can greatly affect study conclusions and program evaluations. Selection of LTF definitions should be based on the study outcome, available data on clinical encounters, and the patients' visit schedules; we suggest some general guidelines.

Keywords: HIV; chronic disease; cohort studies; long-term care; lost to follow-up; program evaluation.

Figure 1.

Seventeen definitions of lost to follow-up used in the literature applied to data from a single, rural Mozambican cohort, 2006–2011. Subfigures demonstrate the following: cumulative incidence of LTF (A); cumulative incidence of AIDS-defining events (ADE) (B); and probability of death at 24 months for each definition (C). AIDS, acquired immunodeficiency syndrome; LTF, lost to follow-up.

Figure 2.

Impact of varying specific components of the lost to follow-up definition, Mozambican cohort, 2006–2011. We investigated the impact of various components of the definition of LTF on estimates. All estimates are centered at a definition that classifies patients as LTF if they go 180 days from their last visit without any encounter (180 days, any encounters, prospective, time from last visit). The rows demonstrate the sensitivity of results to variation in these choices: The top row varies the length of time, the second row (from the top) varies what qualifies as a clinic visit, the third row compares prospective and retrospective definitions, and the bottom row compares time from last visit with time from missed visit. The columns correspond to the different study outcomes: The first column contains the cumulative incidence of LTF, the second column contains the cumulative incidence of AIDS-defining events (ADE), and the third column contains the probability of death. AIDS, acquired immunodeficiency syndrome; ART, antiretroviral therapy; LTF, lost to follow-up.

Figure 3.

Correcting 1-year mortality for lost to follow-up, Mozambican cohort, 2006–2011. Subfigures demonstrate the following: cumulative incidence of LTF at 12 months (A); probability of death at 12 months (B); and nomogram-adjusted probability of death at 12 months (C). LTF, lost to follow-up.