Regression discontinuity designs are underutilized in medicine, epidemiology, and public health: a review of current and best practice

AbstractObjectivesRegression discontinuity (RD) designs allow for rigorous causal inference when patients receive a treatment based on scoring above or below a cutoff point on a continuously measured variable. We provide an introduction to the theory of RD and a systematic review and assessment of the RD literature in medicine, epidemiology, and public health.Study Design and SettingWe review the necessary conditions for valid RD results, provide a practical guide to RD implementation, compare RD to other methodologies, and conduct a systematic review of the RD literature in PubMed.ResultsWe describe five key elements of analysis all RD studies should report, including tests of validity conditions and robustness checks. Thirty two empirical RD studies in PubMed met our selection criteria. Most of the 32 RD articles analyzed the effectiveness of social policies or mental health interventions, with only two evaluating clinical interventions to improve physical health. Seven out of the 32 studies reported on all the five key elements.ConclusionIncreased use of RD provides an exciting opportunity for obtaining unbiased causal effect estimates when experiments are not feasible or when we want to evaluate programs under “real-life” conditions. Although treatment eligibility in medicine, epidemiology, and public health is commonly determined by threshold rules, use of RD in these fields has been very limited until now

Regression Discontinuity Designs in Epidemiology: Causal Inference Without Randomized Trials

When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007–2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/μL CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45–0.94]) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology

Determinants of the Level of Revenue of Tourist Enterprises within the North Coastal Region of Kenya

Revenue of produced goods and/or provided services is determined by the volume of sales, prices of particular products, variety of products, ways of invoicing and period of payment. The current study was carried out at the north coastal region among tourist enterprises to establish factors that influence the amount of revenue they generate per year. The target population involved all enterprises relying on tourists for their business. They include hotel accommodation facilities, curio shops and tour companies. Simple random sampling technique was used to select a final sample of 97 enterprises, whose owners were given self administered questionnaires. Afterwards a regression on determinants of revenue by tourist enterprises was expressed as Y= ?o + ?1X1+ ?2X2+ …?n Xn+ ?; Where: Y – is the dependant variable; X1-n – are the independent variables; ?0 – is the constant ?1-n – are the regression coefficients or change induced in Y by each X,         while ? is the error. The results indicated that the net monthly income of enterprises was determined by the age of the enterprise (? = 0.169, p = 0.001), the location of the business (? = 0.149, p = 0.038) and the number of employees within the enterprise (? = 0.703, p < 0.0005). Therefore findings indicated that the main determinants of revenue for tourist enterprises at Kenya’s north coast were the age of the business, business location and the number of employees. Keywords: Tourist enterprises; Determinants of revenue; Firm; Tourist expenditure

Length of secondary schooling and risk of HIV infection in Botswana: evidence from a natural experiment

Background An estimated 2·1 million individuals are newly infected with HIV every year. Cross-sectional and longitudinal studies have reported confl icting evidence for the association between education and HIV risk, and no randomised trial has identifi ed a causal eff ect for education on HIV incidence. We aimed to use a policy reform in secondary schooling in Botswana to identify the causal eff ect of length of schooling on new HIV infection. Methods Data for HIV biomarkers and demographics were obtained from the nationally representative household 2004 and 2008 Botswana AIDS Impact Surveys (N=7018). In 1996, Botswana reformed the grade structure of secondary school, expanding access to grade ten and increasing educational attainment for aff ected cohorts. Using exposure to the policy reform as an instrumental variable, we used two-stage least squares to estimate the causal eff ect of years of schooling on the cumulative probability that an individual contracted HIV up to their age at the time of the survey. We also assessed the cost-eff ectiveness of secondary schooling as an HIV prevention intervention in comparison to other established interventions. Findings Each additional year of secondary schooling caused by the policy change led to an absolute reduction in the cumulative risk of HIV infection of 8·1 percentage points (p=0·008), relative to a baseline prevalence of 25·5% in the pre-reform 1980 birth cohort. Eff ects were particularly large in women (11·6 percentage points, p=0·046). Results were robust to a wide array of sensitivity analyses. Secondary school was cost eff ective as an HIV prevention intervention by standard metrics (cost per HIV infection averted was US$27 753). Interpretation Additional years of secondary schooling had a large protective eff ect against HIV risk in Botswana, particularly for women. Increasing progression through secondary school could be a cost-eff ective HIV prevention measure in HIV-endemic settings, in addition to yielding other societal benefi ts. Funding Takemi Program in International Health at the Harvard T.H.Chan School of Public Health, Belgian American Educational Foundation, Fernand Lazard Foundation, Boston University, National Institutes of Health

Quasi-experiments to establish causal effects of HIV care and treatment and to improve the cascade of care

Purpose of review Randomized, population-representative trials of clinical interventions are rare. Quasi-experiments have been used successfully to generate causal evidence on the cascade of HIV care in a broad range of real-world settings. Recent findings Quasi-experiments exploit exogenous, or quasi-random, variation occurring naturally in the world or because of an administrative rule or policy change to estimate causal effects. Well designed quasi-experiments have greater internal validity than typical observational research designs. At the same time, quasi-experiments may also have potential for greater external validity than experiments and can be implemented when randomized clinical trials are infeasible or unethical. Quasi-experimental studies have established the causal effects of HIV testing and initiation of antiretroviral therapy on health, economic outcomes and sexual behaviors, as well as indirect effects on other community members. Recent quasi-experiments have evaluated specific interventions to improve patient performance in the cascade of care, providing causal evidence to optimize clinical management of HIV. Summary Quasi-experiments have generated important data on the real-world impacts of HIV testing and treatment and on interventions to improve the cascade of care. With the growth in large-scale clinical and administrative data, quasi-experiments enable rigorous evaluation of policies implemented in real-world settings

Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

This version is the Accepted Manuscript and is published in final edited form as: AIDS. 2017 January 02; 31(1): 147–157. doi:10.1097/QAD.0000000000001307OBJECTIVE: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa. DESIGN: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART. METHODS: We evaluated the frequency of stavudine use and SDS by calendar year 2004-2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART. RESULTS: In all, 33 441 (8.9%; 95% confience interval 8.7-8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20-95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75-85% decrease in the hazards of SDS when compared to stavudine. CONCLUSION: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine