An IV for the RCT: using instrumental variables to adjust for treatment contamination in randomised controlled trials

Although the randomised controlled trial is the “gold standard” for studying the efficacy and safety of medical treatments, it is not necessarily free from bias. When patients do not follow the protocol for their assigned treatment, the resultant “treatment contamination” can produce misleading findings. The methods used historically to deal with this problem, the “as treated” and “per protocol” analysis techniques, are flawed and inaccurate. Intention to treat analysis is the solution most often used to analyse randomised controlled trials, but this approach ignores this issue of treatment contamination. Intention to treat analysis estimates the effect of recommending a treatment to study participants, not the effect of the treatment on those study participants who actually received it. In this article, we describe a simple yet rarely used analytical technique, the “contamination adjusted intention to treat analysis,” which complements the intention to treat approach by producing a better estimate of the benefits and harms of receiving a treatment. This method uses the statistical technique of instrumental variable analysis to address contamination. We discuss the strengths and limitations of the current methods of addressing treatment contamination and the contamination adjusted intention to treat technique, provide examples of effective uses, and discuss how using estimates generated by contamination adjusted intention to treat analysis can improve clinical decision making and patient care

Providing clinicians with a patient’s 10-year cardiovascular risk improves their statin prescribing: a true experiment using clinical vignettes

Abstract Background Statins are effective for primary prevention of cardiovascular (CV) disease, the leading cause of death in the world. Multinational guidelines emphasize CV risk as an important factor for optimal statin prescribing. However, it’s not clear how primary care providers (PCPs) use this information. The objective of this study was to determine how primary care providers use information about global CV risk for primary prevention of CV disease. Methods A double-blinded, randomized experiment using clinical vignettes mailed to office-based PCPs in the United States who were identified through the American Medical Association Physician Masterfile in June 2012. PCPs in the control group received clinical vignettes with all information on the risk factors needed to calculate CV risk. The experimental group received the same vignettes in addition to the subject’s 10-year calculated CV risk (Framingham risk score). The primary study outcome was the decision to prescribe a statin. Results Providing calculated CV risk to providers increased statin prescribing in the two high-risk cases (CV risk > 20%) by 32 percentage points (41% v. 73%; 95% CI = 23-40, p <0.001; relative risk [RR] = 1.78) and 16 percentage points (12% v. 27%, 95% CI 8.5-22.5%, p <0.001; RR = 2.25), and decreased statin prescribing in the lowest risk case (CV risk = 2% risk) by 9 percentage points [95% CI = 1.00-16.7%, p = 0.003, RR = 0.88]. Fewer than 20% of participants in each group reported routinely calculating 10-year CV risk in their patients. Conclusions Providers do not routinely calculate 10-year CV risk for their patients. In this vignette experiment, PCPs undertreated low LDL, high CV risk patients. Giving providers a patient’s calculated CV risk improved statin prescribing. Providing PCPs with accurate estimates of patient CV risk at the point of service has the potential to improve the efficiency of statin prescribing.http://deepblue.lib.umich.edu/bitstream/2027.42/134534/1/12872_2013_Article_871.pd

Can risk modelling improve treatment decisions in asymptomatic carotid stenosis?

Abstract Background Carotid endarterectomy (CEA) is routinely performed for asymptomatic carotid stenosis, yet its average net benefit is small. Risk stratification may identify high risk patients that would clearly benefit from treatment. Methods Retrospective cohort study using data from the Asymptomatic Carotid Atherosclerosis Study (ACAS). Risk factors for poor outcomes were included in backward and forward selection procedures to develop baseline risk models estimating the risk of non-perioperative ipsilateral stroke/TIA. Baseline risk was estimated for all ACAS participants and externally validated using data from the Atherosclerosis Risk in Communities (ARIC) study. Baseline risk was then included in a treatment risk model that explored the interaction of baseline risk and treatment status (CEA vs. medical management) on the patient-centered outcome of any stroke or death, including peri-operative events. Results Three baseline risk factors (BMI, creatinine and degree of contralateral stenosis) were selected into our baseline risk model (c-statistic 0.59 [95% CI 0.54–0.65]). The model stratified absolute risk between the lowest and highest risk quintiles (5.1% vs. 12.5%). External validation in ARIC found similar predictiveness (c-statistic 0.58 [0.49–0.67]), but poor calibration across the risk spectrum. In the treatment risk model, CEA was superior to medical management across the spectrum of baseline risk and the magnitude of the treatment effect varied widely between the lowest and highest absolute risk quintiles (3.2% vs. 10.7%). Conclusion Even modestly predictive risk stratification tools have the potential to meaningfully influence clinical decision making in asymptomatic carotid disease. However, our ACAS model requires target population recalibration prior to clinical application.https://deepblue.lib.umich.edu/bitstream/2027.42/152135/1/12883_2019_Article_1528.pd

Medication cost problems among chronically ill adults in the US: did the financial crisis make a bad situation even worse?

A national internet survey was conducted between March and April 2009 among 27,302 US participants in the Harris Interactive Chronic Illness Panel. Respondents reported behaviors related to cost-related medication non-adherence (CRN) and the impacts of medication costs on other aspects of their daily lives. Among respondents aged 40–64 and looking for work, 66% reported CRN in 2008, and 41% did not fill a prescription due to cost pressures. More than half of respondents aged 40–64 and nearly two-thirds of those in this group who were looking for work or disabled reported other impacts of medication costs, such as cutting back on basic needs or increasing credit card debt. More than one-third of respondents aged 65+ who were working or looking for work reported CRN. Regardless of age or employment status, roughly half of respondents reporting medication cost hardship said that these problems had become more frequent in 2008 than before the economic recession. These data show that many chronically ill patients, particularly those looking for work or disabled, reported greater medication cost problems since the economic crisis began. Given links between CRN and worse health, the financial downturn may have had significant health consequences for adults with chronic illness

Association between hospital case volume and the use of bronchoscopy and esophagoscopy during head and neck cancer diagnostic evaluation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102212/1/cncr28379.pd

Informal Caregiving for Diabetes and Diabetic Complications Among Elderly Americans

Objectives: Little is known regarding the amount of time spent by unpaid caregivers providing help to elderly individuals for disabilities associated with diabetes mellitus (DM). We sought to obtain nationally representative estimates of the time, and associated cost, of informal caregiving provided to the elderly with diabetes, and to determine the complications of DM that contribute most significantly to the subsequent need for informal care. Methods: We estimated multivariable regression models using data from the 1993 Asset and Health Dynamics (AHEAD) Study, a nationally representative survey of people aged 70 or older (N=7,443), to determine the weekly hours of informal caregiving and imputed cost of caregiver time for community-dwelling elderly with and without a diagnosis of DM. Results: Those without DM received an average of 6.1 hours per week of informal care, those with DM taking no medications received 10.5 hours, those with DM taking oral medications received 10.1 hours, and those with DM taking insulin received 14.4 hours of care (P

Adherence to Competing Strategies for Colorectal Cancer Screening Over 3 Years

We have shown that, in a randomized trial comparing adherence to different colorectal cancer (CRC) screening strategies, participants assigned to either fecal occult blood testing (FOBT) or given a choice between FOBT and colonoscopy had significantly higher adherence than those assigned to colonoscopy during the first year. However, how adherence to screening changes over time is unknown

Interhospital Transfers Among Medicare Beneficiaries Admitted for Acute Myocardial Infarction at Nonrevascularization Hospitals

Background—Patients with acute myocardial infarction (AMI) who are admitted to hospitals without coronary revascularization are frequently transferred to hospitals with this capability, yet we know little about the basis for how such revascularization hospitals are selected. Methods and Results—We examined interhospital transfer patterns in 71 336 AMI patients admitted to hospitals without revascularization capabilities in the 2006 Medicare claims using network analysis and regression models. A total of 31 607 (44.3%) AMI patients were transferred from 1684 nonrevascularization hospitals to 1104 revascularization hospitals. Median time to transfer was 2 days. Median transfer distance was 26.7 miles, with 96.1% within 100 miles. In 45.8% of cases, patients bypassed a closer hospital to go to a farther hospital that had a better 30-day risk standardized mortality rates. However, in 36.8% of cases, another revascularization hospital with lower 30-day risk-standardized mortality was actually closer to the original admitting nonrevascularization hospital than the observed transfer destination. Adjusted regression models demonstrated that shorter transfer distances were more common than transfers to the hospitals with lowest 30-day mortality rates. Simulations suggest that an optimized system that prioritized the transfer of AMI patients to a nearby hospital with the lowest 30-day mortality rate might produce clinically meaningful reductions in mortality. Conclusions—More than 40% of AMI patients admitted to nonrevascularization hospitals are transferred to revascular- ization hospitals. Many patients are not directed to nearby hospitals with the lowest 30-day risk-standardized mortality, and this may represent an opportunity for improvement. (Circ Cardiovasc Qual Outcomes. 2010;3:468-475.)This work was supported by 1K08HL091249-01 from the NIH/ NHLBI and used the Measurement Core of the Michigan Diabetes Research and Training Center (NIH/NIDDK, P60DK-20572). This project was also funded in part under a grant from the Pennsylvania Department of Health, which specifically disclaims responsibility for any analyses, interpretations, or conclusions. The funders were not involved in study design, interpretation, or the decision to publish.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78005/1/10.I.Circ.Outcomes.pd