A gentle introduction to instrumental variables

Instrumental variables (IV) is a central strategy for identifying causal effects in absence of randomized experiments. Clinicians and epidemiologists may find the intuition of IV easy to grasp by comparison to randomized experiments. Randomization is an ideal IV because treatment is assigned randomly, and hence unaffected by everything else. IV methods in nonexperimental settings mimic a randomized experiment by using a source of “as good as” random variation in treatment instead. The main challenge with IV designs is to find IVs that are as good as randomization. Discovering potential IVs require substantive knowledge and an understanding of design principles. Moreover, IV methods recover causal effects for a subset of the population who take treatment when induced by the IV. Sometimes these estimates are informative, other times their relevance is questionable. We provide an introduction to IV methods in clinical epidemiology. First, we introduce the main principles and assumptions. Second, we present practical examples based on Mendelian randomization and provider preference and refer to other common IVs in health. Third, practical steps in IV analysis are presented. Fourth, the promise and perils of IV methods are discussed. Finally, we suggest further readings.publishedVersio

Preference-based instrumental variables in health research rely on important and underreported assumptions: a systematic review

Objective: Preference-based instrumental variables (PP IV) designs can identify causal effects when patients receive treatment due to variation in providers’ treatment preference. We offer a systematic review and methodological assessment of PP IV applications in health research. Study Design and Setting: We included studies that applied PP IV for evaluation of any treatment in any population in health research (PROSPERO: CRD42020165014). We searched within four databases (Medline, Web of Science, ScienceDirect, SpringerLink) and four journals (including full-text and title and abstract sources) between January 1, 1998, and March 5, 2020. We extracted data on areas of applications and methodology, including assumptions using Swanson and Hernan’s (2013) guideline. Results: We included 185 of 1087 identified studies. The use of PP IV has increased, being predominantly used for treatment effects in cancer, cardiovascular disease, and mental health. The most common PP IV was treatment variation at the facility-level, followed by physician- and regional-level. Only 12 percent of applications report the four main assumptions for PP IV. Selection on treatment may be a potential issue in 46 percent of studies. Conclusion: The assumptions of PP IV are not sufficiently reported in existing work. PP IV studies should use reporting guidelines

A meta-regression of the impact of policy on the efficacy of individual placement and support

Objective: Individual placement and support (IPS) has shown consistently better outcomes on competitive employment for patients with severe mental illness than traditional vocational rehabilitation. The evidence for efficacy originates from few countries, and generalization to different countries has been questioned. This has delayed implementation of IPS and led to requests for country-specific RCTs. This meta-analysis examines if evidence for IPS efficacy can be generalized between rather different countries. Methods: A systematic search was conducted according to PRISMA guidelines to identify RCTs. Overall efficacy was established by meta-analysis. The generalizability of IPS efficacy between countries was analysed by random-effects meta-regression, employing country- and date-specific contextual data obtained from the OECD and the World Bank. Results: The systematic review identified 27 RCTs. Employment rates are more than doubled in IPS compared with standard vocational rehabilitation (RR 2.07 95% CI 1.82–2.35). The efficacy of IPS was marginally moderated by strong legal protection against dismissals. It was not moderated by regulation of temporary employment, generosity of disability benefits, type of integration policies, GDP, unemployment rate or employment rate for those with low education. Conclusions: The evidence for efficacy of IPS is very strong. The efficacy of IPS can be generalized between countries

Long term outcomes and causal modelling of compulsory inpatient and outpatient mental health care using Norwegian registry data: protocol for a controversies in psychiatry research project

Objectives: Compulsory mental health care includes compulsory hospitalisation and outpatient commitment with medication treatment without consent. Uncertain evidence of the effects of compulsory care contributes to large geographical variations and a controversy on its use. Some argue that compulsion can rarely be justified and should be reduced to an absolute minimum, while others claim compulsion can more frequently be justified. The limited evidence base has contributed to variations in care that raise issues about the quality/appropriateness of care as well as ethical concerns. To address the question whether compulsory mental health care results in superior, worse or equivalent outcomes for patients, this project will utilise registry‐ based longitudinal data to examine the effect of compulsory inpatient and outpatient care on multiple outcomes, including suicide and overall mortality; emergency care/injuries; crime and victimisation; and participation in the labour force and welfare dependency. Methods: By using the natural variation in health providers' preference for compulsory care as a source of quasi‐randomisation we will estimate causal effects of compulsory care on short‐ and long‐term trajectories. Conclusions: This project will provide valuable insights for service providers and policy makers in facilitating high quality clinical care pathways for a high risk population group

The role of welfare regimes in the relationship between childhood economic stress and adult health: a multilevel study of 20 European countries

Childhood economic conditions are important for adult health, and welfare regimes may modify this relationship by altering exposure to social determinants of health. We examine the association between childhood economic stress (CES) and self-rated health (SRH) and cancer (any type), and how welfare regimes may influence these associations. We used data from European Social Survey round 7. Our study is based on 30 024 individuals between 25 to 75 years from 20 European countries grouped into five welfare regimes (Scandinavian, Anglo-Saxon, Bismarckian, Southern and Eastern). Multilevel models were used to assess the association between CES and SRH/cancer, and interactions between CES and welfare regimes. CES increased the risk of poor SRH (RR 1.41, 95% CI 1.29–1.54) and cancer (RR 1.19, 95% CI 1.02–1.37). Controlling for adult socioeconomic status slightly reduced risk for poor SRH, but not cancer. CES increased the probability of poor SRH in the Southern and Eastern regime, and the probability of cancer in the Anglo-Saxon regime, relative to the Scandinavian regime. Childhood economic stress increases the risk of poor self-rated health and cancer. More comprehensive welfare states mitigate these associations, which emphasizes the impact of welfare policies on long-term health outcomes of childhood economic conditions

Geographical variation in ADHD: do diagnoses refect symptom levels?

Rates of ADHD diagnosis vary across regions in many countries. However, no prior study has investigated how much within-country geographic variation in ADHD diagnoses is explained by variation in ADHD symptom levels. We examine whether ADHD symptom levels explain variation in ADHD diagnoses among children and adolescents using nationwide survey and register data in Norway. Geographical variation in incidence of ADHD diagnosis was measured using Norwegian registry data from the child and adolescent mental health services for 2011–2016. Geographical variation in ADHD symptom levels in clinics’ catchment areas was measured using data from the Norwegian mother, father and child cohort study for 2011–2016 (n = 39,850). Cross-sectional associations between ADHD symptom levels and the incidence of ADHD diagnoses were assessed with fractional response models. Geographical variation in ADHD diagnosis rates is much larger than what can be explained by geographical variation in ADHD symptoms levels. Treatment in the Norwegian child and adolescent mental health services is free, universally available upon referral, and practically without competition from the private sector. Factors beyond health care access and unequal symptom levels seem responsible for the geographical variation in ADHD diagnosis