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PubMed2006

Is some provider advice on smoking cessation better than no advice? An instrumental variable analysis of the 2001 National Health Interview Survey.

RESEARCH OBJECTIVE: To estimate the effect of provider advice in routine clinical contacts on patient smoking cessation outcome. DATA SOURCE: The Sample Adult File from the 2001 National Health Interview Survey. We focus on adult patients who were either current smokers or quit during the last 12 months and had some contact with the health care providers or facilities they most often went to for acute or preventive care. STUDY DESIGN: We estimate a joint model of self-reported smoking cessation and ever receiving advice to quit during medical visits in the past 12 months. Because providers are more likely to advise heavier smokers and/or patients already diagnosed with smoking-related conditions, we use provider advice for diet/nutrition and for physical activity reported by the same patient as instrumental variables for smoking cessation advice to mitigate the selection bias. We conduct additional analyses to examine the robustness of our estimate against the various scenarios by which the exclusion restriction of the instrumental variables may fail. PRINCIPAL FINDINGS: Provider advice doubles the chances of success in (self-reported) smoking cessation by their patients. The probability of quitting by the end of the 12-month reference period increased from 6.9 to 14.7 percent, an effect that is of both statistical (p < .001) and clinical significance. CONCLUSIONS: Provider advice delivered in routine practice settings has a substantial effect on the success rate of smoking cessation among smoking patients. Providing advice consistently to all smoking patients, compared with routine care, is more effective than doubling the federal excise tax and, in the longer run, likely to outperform some of the other tobacco control policies such as banning smoking in private workplaces.

Adult↗
PubMed2004

Instrumental variables technique: cigarette price provided better estimate of effects of smoking on SF-12.

OBJECTIVE: Debate surrounds the usefulness of the instrumental variables (IV) technique for medical research. The choice of an instrument for the technique has been contentious. This study estimated the effects of smoking on physical functional status. We chose an especially valid and strong instrument: cigarette price. STUDY DESIGN AND SETTING: The data were a nationally representative cross-sectional sample of 34,288 persons aged 30 to 91 in 1996-1997. The sample was drawn from the Community Tracking Study. Number of cigarettes smoked per day was predicted by the average cigarette price for the state in which the subject resided. The outcome measure was physical functional status and was measured by the SF-12 physical functional index. RESULTS: In multivariable models we found the following: cigarettes per day was strongly and negatively associated with the SF-12 index (P<.001); cigarette price was strongly and negatively associated with cigarettes per day (P=.002); the predicted cigarettes per day (the IV) was strongly and negatively associated with the SF-12 index in linear regression and tobit regression (P=.047 and P=.021). CONCLUSION: Estimated coefficients from the IV method suggested that the effect of smoking on physical functional status was substantially larger than estimates that relied on conventional methods.

Adult↗
PubMed2007

Instrumental variables and interactions in the causal analysis of a complex clinical trial.

We consider the application of instrumental variable techniques in a longitudinal clinical trial in paediatric HIV/AIDS, with a substantial degree of non-compliance to randomized treatment (Nelfinavir versus placebo) and with left censoring of the outcome variable (HIV RNA concentration). We consider in detail the assumptions and implications behind the inclusion and exclusion of interactions between randomized arm and baseline covariates in modelling actual treatment received, and between treatment and baseline covariates in modelling outcome. Estimated treatment effects were sensitive to inclusion of interactions, and we show how such sensitivity can be explored and explained.

Anti-HIV Agents↗
PubMed1998

Who is the marginal patient? Understanding instrumental variables estimates of treatment effects.

OBJECTIVE: To clarify the issues of generalizability arising from the use of instrumental variable (IV) methods to estimate treatment effects in nonexperimental medical outcome studies. DATA SOURCE: We generate Monte Carlo data designed to resemble typical data sets where detailed health status information is unavailable and the treatment assignment process is unobserved. The model used to generate our data makes the realistic assumption that unobservable health status characteristics of patients influence the treatment assignment process and the effectiveness of treatment. STUDY DESIGN: We use Monte Carlo data to illustrate the circumstances where IV estimates generalize to an unobservable patient subpopulation and those where IV estimates generalize to the entire patient population represented by the sample used in the analysis. We also simulate the effect of two policy changes that affect practice patterns. Further, we show that IV estimates are useful for predicting the effect of these changes on treatment effectiveness when the subpopulation to which the IV estimate refers is the same or very similar to the population whose treatment status is affected by the policy change. CONCLUSIONS: Health services researchers cannot take for granted that IV estimates generalize to the same population represented by the sample used for analysis. Instead, researchers must rely on their knowledge of clinical practice and theory regarding the treatment assignment process in interpreting their results and in predicting the effect of changes in practice patterns.

Analysis of Variance↗
PubMed2005

Estimating treatment effects from randomized clinical trials with noncompliance and loss to follow-up: the role of instrumental variable methods.

Perfectly implemented randomized clinical trials, particularly of complex interventions, are extremely rare. Almost always they are characterized by imperfect adherence to the randomly allocated treatment and variable amounts of missing outcome data. Here we start by describing a wide variety of examples and then introduce instrumental variable methods for the analysis of such trials. We concentrate mainly on situations in which compliance is all or nothing (either the patient receives the allocated treatment or they do not--in the latter case they may receive no treatment or a treatment other than the one allocated). The main purpose of the review is to illustrate the use of latent class (finite mixture) models, using maximum likelihood, for complier-average causal effect estimation under varying assumptions concerning the mechanism of the missing outcome data.

Depression↗
PubMed1994

Does more intensive treatment of acute myocardial infarction in the elderly reduce mortality? Analysis using instrumental variables.

OBJECTIVE: To determine the effect of more intensive treatments on mortality in elderly patients with acute myocardial infarction (AMI). DESIGN: Analysis of incremental treatment effects using differential distances as instrumental variables to account for unobserved case-mix variation (selection bias) in observational Medicare claims data (1987 through 1991). MAIN OUTCOME MEASURES: Survival to 4 years after AMI. RESULTS: Patients who receive different treatments differ in observable and unobservable health characteristics, biasing estimates of treatment effects based on standard methods of adjusting for observable differences. Patients' differential distances to alternative types of hospitals are strong independent predictors of how intensively an AMI patient will be treated and appear uncorrelated with health status. Thus, differential distances approximately randomize patients to different likelihoods of receiving intensive treatments. Comparisons of patient groups that differ only in differential distances show that the impact on mortality at 1 to 4 years after AMI of the incremental ("marginal") use of invasive procedures in Medicare patients was at most 5 percentage points; this gain was achieved during the first day of hospitalization and therefore appears attributable to treatments other than the procedures. Admission to a hospital treating a high volume of AMI patients was associated with an effect on mortality at 4 years of less than 1 percentage point, again arising on day 1. Patients living in rural areas experienced acute mortality that was an additional 0.6 percentage-point higher, after controlling for less access to intensive treatments. CONCLUSIONS: For elderly patients with AMI, the aspects of treatment most affecting long-term survival relate to care within the first 24 hours of admission. The survival benefits from greater use of catheterization and revascularization procedures appear minimal in marginal patients.

Aged↗
PubMed1999

Estimating the quality of care in hospitals using instrumental variables.

Mortality rates are a widely used measure of hospital quality. A central problem with this measure is selection bias: simply put, severely ill patients may choose high quality hospitals. We control for severity of illness with an instrumental variables (IV) framework using geographic location data. We use IV to examine the quality of pneumonia care in Southern California from 1989 to 1994. We find that the IV quality estimates are markedly different from traditional GLS estimates, and that IV reveals different determinants of quality. Econometric tests suggest that the IV model is appropriately specified, that the GLS model is inconsistent.

California↗
PubMed1992

[Risk stratification in patients with a first myocardial infarct based on simple clinico-instrumental variables].

UNLABELLED: It is an acknowledged fact that the prognosis for patients with a first myocardial infarction depends mainly on the degree of residual left ventricle function. We wanted to evaluate the importance that certain simple clinical and instrumental variables can have in stratifying post-infarction cardiovascular risk with particular emphasis on chronic obstructive lung disease (COLD). We selected 97 out of the 512 patients treated in the coronary intensive care unit (CICU) from February 1, 1988 to October 31, 1990 according to the following criteria: First myocardial infarction; no cardiogenic shock; no serious concomitant diseases with considered negative prognosis within 6 months. The following variables were considered for all the patients: age; sex; positive family history for ischemic heart disease; history of diabetes mellitus; arterial hypertension; previous cerebrovascular incident; history of obstructive arteriopathy of the lower limbs, of angor and COLD. The following tests were performed on all the patients: echocardiogram prior to discharge form the CICU; angiocardioscintigraphy with Tc-99 between the 20th and 30th day following the acute event; bicycle ergometer stress test on the 30th day. END POINTS: general mortality; cardiac mortality; non-fatal reinfarction; residual angina at 3 months. All the patients were treated with aspirin (325 mg/die) and/or heparin (12,500 units subcutaneously). All 97 patients were monitored for a mean follow-up time of 19.8 months. General mortality was 2.08% (for reinfarction) 24 (24.7%) non-fatal cardiac events.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1998

[The evaluation of parameters pertinent to the excitation in aurora with a time-domain recursive instrumental-variables algorithm].

The time-domain expression and spectral analysis of the combined direct and indirect excitation process in aurora are described. The technique to evaluate the parameters pertinent to the excitation in aurora with a time-domain recursive instrumental-variables algorithm was studied. The parameters thus determined compare favourably with those evaluated by means of a non-recursive cross-spectral technique. A modification to the algorithm allows the tracking of changes in the excitation mechanism by evaluating parameters which vary in time. Processing of real auroral photometric measurements with this method has established the existence of such changes and demonstrated their time history.

English Abstract↗
PubMed1999

An in-vitro method for buccal adhesion studies: importance of instrument variables.

A method using a texture analyzer equipment and chicken pouch as the biological tissue was investigated for measuring the bioadhesive properties of polymers under simulated buccal conditions. The method was evaluated using two polymers, namely Carbopol 974P and Methocel K4M while the instrument variables studied included the contact force, contact time and speed of withdrawal of the probe from the tissue. The parameters measured were the work of adhesion and peak detachment force. Longer contact time and faster probe speed not only gave better reproducibility of results, but also better sensitivities for both parameters measured. On the other hand, a certain level of contact force was found essential for achieving good bioadhesion, above which there was no further contribution to the bioadhesion process. When the method was applied to determine the bioadhesiveness of several polymers, the values obtained for the work of adhesion and peak detachment force were quite consistent in the ranking of the polymers. The Carbopols were found to have the highest values, followed by gelatin, sodium carboxymethyl celluloses and hydroxypropylmethyl celluloses. On the other hand, Alginic acid, Eudragit RLPO and RSPO, and Chitosan appeared to have low bioadhesive values.

Adhesives↗
PubMedDate not supplied

The instrumental variable method to study self-selection mechanism: a case of influenza vaccination.

OBJECTIVE: To assess whether estimates of the effectiveness of influenza vaccination in reducing rates of hospitalizations and all-cause mortality derived from cross-sectional data could be improved by applying the instrumental variable (IV) method to data representing the community-dwelling elderly population in the United States in order to adjust for self-selection bias. METHODS: Secondary data analysis, using the 1996-97 Medicare Current Beneficiary Survey data. First, using single-equation probit regressions this study analyzed influenza-related hospitalization and death due to all causes predicted by vaccination status, which was measured by claims or survey data. Second, to adjust for potential self-selection of the vaccine receipt, for example, higher vaccination rates among high-risk individuals, bivariate probit (BVP) models and two-stage least squares (2SLS) models were employed. The IV was having either arthritis or gout. RESULTS: In single-equation probit models, vaccination appeared to be ineffective or even to increase the probability of adverse outcomes. Based on BVP and 2SLS models, vaccination was demonstrated to be effective in reducing influenza-related hospitalization by at least 31%. The BVP model results implied significant self-selection in the single-equation probit models. CONCLUSIONS: Adjusting for self-selection, BVP analyses yielded vaccine effectiveness estimates for a nationally representative cross-sectional sample of the community-dwelling elderly population that are consistent with previous estimates based on randomized controlled trials, prospective cohort studies, and meta-analyses. This result suggests that analyses with 2SLS and BVP in particular may be useful for the analysis of observational data regarding prevention in which self-selection is an important potential source of bias.

Aged↗
PubMed2007

Survival advantage associated with treatment of injury at designated trauma centers: a bivariate probit model with instrumental variables.

This article analyzes the effectiveness of designated trauma centers in Florida concerning reduction in the mortality risk of severely injured trauma victims. A bivariate probit model is used to compute the differential impact of two alternative acute care treatment sites. The alternative sites are defined as (1) a nontrauma center (NC) or (2) a designated trauma center (DTC). An instrumental-variables method was used to adjust for prehospital selection bias in addition to the influence of age, gender, race, risk of mortality, and type of injury. Treatment at a DTC was associated with a reduction of 0.13 in the probability of mortality.

Adult↗
PubMed2005

The impact of pediatric intensive care unit volume on mortality: a hierarchical instrumental variable analysis.

OBJECTIVE: To evaluate the relation between annual pediatric intensive care unit (PICU) admission volume and mortality. DESIGN: Nonconcurrent cohort design. SETTING: Pediatric patients included in the most currently available research database from the Pediatric Intensive Care Unit Evaluations (PICUEs). PATIENTS: A total of 34,880 consecutive pediatric admissions to a contemporary volunteer sample of 15 U.S. PICUs. MEASUREMENTS AND MAIN RESULTS: We conducted an instrumental variable analysis and adjusted for similarities between patients admitted to different PICUs using mixed-effects, hierarchical techniques. Case mix and severity of illness was adjusted for using patient-level data and the Pediatric Risk of Mortality, version III (PRISM III). On average, admission to higher-volume PICUs was associated with lower severity-adjusted mortality (odds ratio = 0.68 per 100 patient increase in volume; 95% confidence interval: 0.52-0.89) when volume was analyzed as a linear term; however, when PICU volume was analyzed as a quadratic term, we found the lowest severity-adjusted mortality rates among PICUs with annual admission volumes between 992 and 1,491. Furthermore, lower severity-adjusted mortality rates were primarily found among patients with less than a 10% PRISM III predicted risk of mortality. CONCLUSIONS: Although there is an association between lower severity-adjusted mortality among higher volume PICUs, our data suggest that best outcomes are among mid- to large-sized PICUs. These data support minimum annual admission criteria for PICUs but raise the concern that PICUs with very high annual admission volumes may operate beyond an ideal capacity.

Child↗
PubMed2003

Was breast conserving surgery underutilized for early stage breast cancer? Instrumental variables evidence for stage II patients from Iowa.

OBJECTIVE: To estimate the average survival effects of breast conserving surgery plus irradiation relative to mastectomy for marginal stage II breast cancer patients in Iowa from 1989-1994. DATA SOURCES/DATA SETTING: Secondary linked Iowa SEER Cancer Registry--Iowa Hospital Association discharge abstract data for women in Iowa with stage II breast cancer from 1989-1994. STUDY DESIGN: Observational instrumental variables (IV) analysis. DATA COLLECTION/EXTRACTION METHODS: Women with stage II breast cancer from the Iowa SEER Cancer Registry 1989-1994 who received all of their inpatient care in Iowa were linked with their respective hospital discharge abstracts. PRINCIPAL FINDINGS: Breast conserving surgery plus irradiation decreased survival relative to mastectomy for marginal stage II breast cancer patients in Iowa during the early 1990s. In this study marginal patients were those whose surgery choices were affected by differences in area treatment rates and access to radiation facilities. CONCLUSIONS: If marginal patients are representative of patients whose treatment choices would be affected by changes in treatment rates, an increase in the breast conserving surgery plus irradiation rate for stage II early stage breast cancer patients would have decreased survival in Iowa during the early 1990s. Further research with newer data and broader samples is needed to make more current and specific assessments.

Aged↗
PubMed2006

Estimating the effect of smoking cessation on weight gain: an instrumental variable approach.

OBJECTIVE: To propose and test a method that produces an unbiased estimate of the average effect of smoking cessation on weight gain. Previous estimates may be biased due to unobservable differences in attributes of quitters and continuing smokers. An accurate estimate of weight gain due to cessation is important for policymakers, health managers, clinicians, consumers, and developers of smoking cessation aids. STUDY SETTING: Our analysis consisted of an instrumental variables (IVs) approach in which treatment assignment in randomized smoking cessation trials served as a random source of variation in probability of quitting. DATA COLLECTION: We searched the medical literature for previously conducted smoking cessation trials that contained data suitable for our reanalysis. PRINCIPAL FINDINGS: We identified one trial for our reanalysis, the Lung Health Study, a randomized smoking cessation trial with 5,887 smokers aged 35-60 from 1986 to 1994 in several sites across the United States. In our IV reanalysis, we estimated a 9.7 kg weight gain over 5 years due to cessation, as compared with the conventional estimate of 5.3 kg. CONCLUSIONS: The true effect of smoking cessation on weight gain may be larger than previously estimated. This result indicates the importance of fully understanding the possible weight effects of cessation and underscores the need to accompany cessation programs with weight management interventions. The result, however, does not overturn the conclusion that the net health benefits of quitting are positive and very large. The application of the IV technique we propose is likely to be useful in a variety of contexts in which one is interested in the effect of one health condition on another.

Adult↗
PubMed2000

Do longer postpartum stays reduce newborn readmissions? Analysis using instrumental variables.

OBJECTIVE: To determine the effect of postpartum length of stay on newborn readmission. DATA SOURCES: Secondary data set consisting of newborns born in Washington state in 1989 and 1990. The data set contains information about the characteristics of the newborn and its parents, physician, hospital, and insurance status. STUDY DESIGN: Analysis of the effect of length of stay on the probability of newborn readmission using hour of birth and method of delivery as instrumental variables (IVs) to account for unobserved heterogeneity. Of approximately 150,000 newborns born in Washington in 1989 and 1990, 108,551 (72 percent) were included in our analysis. PRINCIPAL FINDINGS: Newborns with different lengths of stay differ in unmeasured characteristics, biasing estimates based on standard statistical methods. The results of our analyses show that a 12-hour increase in length of stay is associated with a reduction in the newborn readmission rate of 0.6 percentage points. This is twice as large as the estimate obtained using standard statistical (non-IV) methods. CONCLUSION: An increase in the length of postpartum hospital stays may result in a decline in newborn readmissions. The magnitude of this decline in readmissions may be larger than previously thought.

Bias↗
PubMed1994

Measurement error, instrumental variables and corrections for attenuation with applications to meta-analyses.

MacMahon et al. present a meta-analysis of the effect of blood pressure on coronary heart disease, as well as new methods for estimation in measurement error models for the case when a replicate or second measurement is made of the fallible predictor. The correction for attenuation used by these authors is compared to others already existing in the literature, as well as to a new instrumental variable method. The assumptions justifying the various methods are examined and their efficiencies are studied via simulation. Compared to the methods we discuss, the method of MacMahon et al. may have bias in some circumstances because it does not take into account: (i) possible correlations among the predictors within a study; (ii) possible bias in the second measurement; or (iii) possibly differing marginal distributions of the predictors or measurement errors across studies. A unifying asymptotic theory using estimating equations is also presented.

Bias↗
PubMed2003

Does aggressive care following acute myocardial infarction reduce mortality? Analysis with instrumental variables to compare effectiveness in Canadian and United States patient populations.

BACKGROUND: Previous U.S. studies suggest that the incremental ("marginal") use of the aggressive approach to care for acute myocardial infarction (AMI) in patients differing only in their distance to hospitals offering aggressive care may be associated with small mortality benefits. We hypothesized that the marginal benefits should be larger in Canada, as the country is operating on a lower margin because the approach to care is more conservative overall. METHODS: This retrospective study used administrative data of hospital admissions and health services for all patients admitted for a first AMI in Quebec in 1988 (n = 8,674). We used differential distances to hospitals offering aggressive care as instrumental variables when measuring mortality up to four years after AMI. RESULTS: Of the 4,422 subjects who were > or = 65 years old, 11 percent received cardiac catheterization within 90 days after admission. In a previous study that applied similar methodology to the 1987 U.S. Medicare population, 23 percent of subjects received catheterization within 90 days. As in the U.S. study, we found that subjects living closer to hospitals offering aggressive care were more likely to receive aggressive care than subjects living further away (26 percent versus 19 percent received cardiac catheterization within 90 days; 95 percent CI: 5 percent to 9 percent). Unlike the U.S. study, we found no differences in mortality across the "close" versus "far" differential distance groups (unadjusted differences at one year: 1 percent; 95 percent CI: -1 percent to 3 percent). This absence of association held in elderly (> or = 65 years) and younger age groups. Adjusted results also showed no differences between subjects receiving aggressive versus conservative care (at one year: 4 percent; 95 percent CI: -11 percent to 20 percent). CONCLUSIONS: Contrary to our hypothesis, but consistent with results from numerous randomized trials and observational studies, we cannot confirm that, on the margin, the aggressive approach to post-AMI care is associated with mortality benefits in Canada.

Aged↗