Formulary Restrictions Research Articles

Commentaries on health services research

Commentaries on health services research

Antimicrobial Stewardship: The Role of the Patient

The aim of this article is to describe the current state of the patient role in antimicrobial stewardship efforts. There is a global crisis in antimicrobial resistance (AR) for which antimicrobial use is the main driver. Antimicrobial stewardship (AS) is a critical ally in the battle against AR. The extent to which specific AS initiatives are implemented across settings varies considerably; many acute care settings have a formal antimicrobial stewardship program (ASP), but other patient care settings such as outpatient clinics or long-term care facilities are generally in the early phases of developing AS efforts which may include a regional approach encompassing transitions of care. In recognizing that a coordinated care approach across the spectrum of healthcare is essential to improve patient outcomes, there is a renewed and increased push to broaden AS implementation across multiple settings. In the acute care setting, a common characteristic of an ASP is a multidisciplinary team to guide antibiotic decision-making at an individual and a facility level. Efforts often target appropriate use of antimicrobials via formulary restrictions, prescribing decision-support models, education, and audit and feedback of prescribing practices. Patients are not usually included in stewardship efforts. Stewardship literature which includes a patient-role component is limited and focuses primarily on physician-patient communication or educational campaigns to raise public awareness of AS. There is little research exploring direct patient involvement in AS efforts, although there is some evidence that patients are aware of the implications of AR, its link to antimicrobial use, and its impact on health at the population level. Recent work has shown that patients believe there is a role for them in AS efforts; however, there is no guidance on the best approach to achieve patient involvement in AS initiatives and no evidence of the effect of such patient involvement on clinical outcomes. In order to fill the gap in knowledge related to the patient role in AS, we recommend the following for clinicians and researchers:

Financial Toxicity and Societal Costs of Cancer Care: Distinct Problems Require Distinct Solutions.

Control of societal costs can be addressed through clinician education, value-based guidelines and pathways, formulary restrictions, payment reform, and government regulatory decisions but should not be imposed on patients at the point of decision-making in the cancer clinic.

ASP Strategies and Appropriate Antibiotic Use

BackgroundThe Infectious Diseases Society of America (IDSA) recommends hospitals implement antimicrobial stewardship programs (ASP) in order to decrease inappropriate antibiotic use due to the rise in antibiotic-resistant infections. Data are limited on the extent to which different ASP strategies influence appropriate antibiotic use.MethodsWe conducted an online survey in 2016 of U.S. Children’s Hospitals to collect hospital-level information on dedicated ASP effort, ASP monitoring activities, use of audit-feedback, formulary restrictions, rapid diagnostics, etc. During the same period the ASP teams at these hospitals completed 3 point prevalence surveys that documented details on all admitted patients 0–17 years receiving any antibiotics, determined what ASP modifications could be made, and if the antibiotic was appropriate. We employed hierarchical, multivariable logit models to examine which ASP-related, hospital-level strategies were associated with appropriate antibiotic use.ResultsThirty hospitals participated. A total of 6,921 patients were included, representing 10,068 total antibiotics. Of these orders, 8,554 (85.0%) were categorized as appropriate, though this varied across sites (range: 68-92%). Additionally, 78.2% of antibiotics did not have recommended modifications. Appropriate antibiotic use was significantly higher for hospitals that relied on rapid diagnostics (aOR: 1.6; P < 0.001) or monitored their days of therapy (DOT) rate (aOR: 1.4; P < 0.001), whereas the presence of either audit-feedback (aOR: 1.04; P = 0.75) or formulary restrictions (aOR: 0.83; P = 0.059) were not associated. Having annual education for all prescribers had increased likelihood of antibiotics having no modification recommendations (aOR: 1.45; P = 0.037). Total ASP FTE was not correlated with hospital-level percent appropriate use (corr: −0.05; P = 0.79) or antibiotic modification recommendations (corr: −0.08; P = 0.67).ConclusionRoutine monitoring of DOT rates and utilization of rapid diagnostics were associated with appropriate antibiotic use. Additional analysis is needed to understand additional factors that can aid hospitals in developing and maintaining ASPs to reduce inappropriate antibiotic use.Disclosures B. R. Lee, Merck: Grant Investigator, Grant recipient. PCORI: Grant Investigator, Grant recipient. C. Terrill, Merck: Grant Investigator, Research grant Allergan: Grant Investigator, Research grant. J. Newland, Merck: Grant Investigator, Research grant. Allergan: Grant Investigator, Research grant

Impact of Overactive Bladder Step Therapy Policies on Medication Utilization and Expenditures Among Treated Medicare Members.

The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs. To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients. A retrospective cross-sectional study design was utilized. Subjects included individuals enrolled in Humana MAPD plans or PDPs, aged ≥ 65 years, with ≥ 1 prescription for an OAB medication in 2013. Patient demographic characteristics, OAB medication utilization, and pharmacy cost trends in 2013 were described. OAB medication use was calculated as the number of 30-day-supply equivalent medication claims and reported as a percentage of the total number of 30-day-supply equivalent claims across all OAB products. OAB medication expenditures were calculated as a percentage of the sum of pharmacy costs for OAB medications and reported separately for each month and drug during 2013. Temporal trends of OAB medication utilization and expenditures in 2013 were calculated using ordinary least squares regression. Of 194,511 patients, trends in utilization of OAB medications indicated that on average, there was a statistically significant monthly increase in utilization of mirabegron (regression coefficient [B] = 274; P < 0.001; 95% CI: 218, 330), fesoterodine (B = 167; P < 0.001; 95% CI = 129, 205), oxybutynin extended release (ER; B = 357; P = 0.011; 95% CI = 99, 614), and trospium ER (B = 33; P = 0.001; 95% CI = 17, 50) and statistically significant decreases in utilization of solifenacin (B = -202; P = 0.048; 95% CI = -402, -2), tolterodine ER (B = -287; P = 0.002; 95% CI = -437, -137), darifenacin (B = -94; P < 0.001; 95% CI = -128, -61), and trospium immediate release (IR; B = -22; P = 0.001; 95% CI = -32, -12). Total OAB medication expenditures significantly increased an average of 0.12% for each month during the course of 2013 (B = 0.12; P = 0.026; 95% CI = 0.017, -0.223). While monthly oxybutynin IR utilization did not change significantly throughout 2013 (B = 228; P = 0.169; 95% CI = -114, -570), it demonstrated the largest average monthly expenditure increase (B = 0.082; P < 0.001; 95% CI = 0.056, 0.108). When removing oxybutynin IR costs from the total OAB medication costs, the trend in total OAB medication average monthly expenditures was not significant (B = 0.038; P = 0.365; 95% CI = -0.051, -0.126). An over 4-fold per-unit-cost increase for oxybutynin IR was noted. Utilization of 2 branded OAB products increased in the months after ST removal with minimal cost impact. One of the possible reasons total OAB expenditures increased may have been due to the increased cost of the largest-volume generic product, oxybutynin IR. This research was funded by Astellas Pharma Global Development and was conducted as part of the Astellas-Humana Research Collaboration. Ng, Kristy, Schermer, and Bradt are employees of Astellas. Astellas manufactures mirabegron (Myrbetriq) and solifenacin (VESIcare). Abbass, Caplan, Collins, and Suehs are employees of Comprehensive Health Insights, a subsidiary of Humana, which received funding from Astellas for this study. Suehs owns stock in Humana. Chan is an employee of Humana Pharmacy Solutions. Portions of this study were presented as a poster at Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, Florida. Study concept and design were contributed by Ng, Chan, Suehs, and Abbass, along with Collins. Abbass took the lead in data collection, along with Collins and with assistance from Caplan, Chan, and Suehs. Data interpretation was provided by Kristy and Bradt, along with Abbass, Caplan, Ng, Suehs, Collins, and Chan. The manuscript was written primarily by Caplan, along with Schermer, Suehs, and Abbass, and revised by Caplan, Schermer, and Ng, along with the other authors.

Effective Antibiotic Conservation by Emergency Antimicrobial Stewardship During a Drug Shortage.

We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged. Infect Control Hosp Epidemiol 2017;38:356-359.

Antimicrobial stewardship programs that target only high-cost, broad-spectrum antimicrobials miss opportunities to reduce Clostridium difficile infections.

Antimicrobial stewardship programs are promoted as a strategy to reduce Clostridium difficile infections. We implemented an antimicrobial stewardship program comprised of formulary restriction plus prospective audit with feedback for high-cost and broad-spectrum antimicrobials. Subsequently, we reviewed all heath care facility-onset, health care facility-associated C difficile infections. We found that most of these infections were associated with the antecedent receipt of nonaudited, and often unnecessary, antimicrobials.

PHP92 - The 2016 US Payor Landscape: Results from a Survey of Medical and Pharmacy Directors on Formulary Management

To determine the types of approaches preferred by Medical and Pharmacy Directors (MDs+PDs) of US health plans, insurers, and pharmacy-benefit managers to enhance the P&T decision-making process and understand formulary reviews/coverage and changes from prior surveys. Online survey of US MDs+PDs from public/private plans with multiple member-types on: advisor+plan information; formulary coverage and restrictions. Fifty-nine percent of respondents were MDs from National=41.1%; local=38.6%; and regional=30.4%. Clinician-administered products (CAPS, including office-administered infusions/injections) always covered under the medical-benefit (64.3%), 5.4% exclusively under the pharmacy-benefit, the remaining 32.7% benefit coverage was threshold/plan-design based, changes were: not anticipated (70.9%); being implemented (5.4%), expected by 12/16 (14.5%) or by 12/18 (3.6%). Mental health [MH] products were carved-out by 25.9%, conditions with multiple MH-therapies required: generics-first (50%), step-therapy (31.5%) or psychiatrist/specialist care (18.5%). Respondents involved in decisions for: prescription-drugs (All=66.5%,Some=22.4%,None=12.1%) and medical-devices (All=53.7%,threshold-dependent=5.6%,None=40.7%). Parity policies were in place for: All=31.2%;None=20.8%;Mandated-states=20.8%; Commercial-plans=14.6%;Select-plans=10.4%;Medicaid-plans=4.2%; Never heard of=18.7. Affordable-Care-Act (ACA) plans are being eliminated by 21.3% (6.4%=Currently,8.5% Before 12/17) and current ACA family-deductibles were: <$1000(7.9%);$1000-$2499(26.3%);$2500-$4999(28.9%);$5000-$9999(15.8%);>$10000(5.3%). Most were happy with their pharmacy-benefit design, the most requested changes were: Formulary changes (17.1%):Tiering(17.1%);Benefit-alignment (11.4%);and tied at 8.6% Biosimilars, Clinician-involvement; and Evidence-based Medicine (EBM). Cost-Effectiveness Research (CER) results will be used: Care Value=34.6%; Care appropriateness=17.3%; Guideline optimization/improvement=11.5%; Pharmaceutical R&D=1.9%; Medical/pharmacy-benefit management=23.1%; Other=0%; Unsure/None of the above=11.5%. The most common desired P&T process change was tied between no-change and better EBM data (both 31.6%). Most were happy with their medical-benefit, the most request change was moving all drugs to the pharmacy-benefit. Top concerns today and in the future included Oncology; Diabetes and Cardiovascular diseases. The managed care P&T Committee decision-making process is undergoing a series of changes. Medical and pharmacy directors, who commonly serve as P&T Committee members, have distinct opinions as to how to alter the process to adapt to these influences.

Society Launches Quality Prescribing Campaign

Society Launches Quality Prescribing Campaign

Economic Outcomes Associated with a Pharmacist-Adjudicated Formulary Consult Service in a Veterans Affairs Medical Center.

Several cost analysis studies have been conducted looking at clinical and economic outcomes associated with clinical pharmacist services in a variety of health care settings. However, there is a paucity of data regarding the economic impact of clinical pharmacist involvement in formulary management at the hospital level. To evaluate economic outcomes of a pharmacist-adjudicated formulary management consult service in a Veterans Affairs (VA) medical center offering outpatient and inpatient services. This VA medical center uses a pharmacist-adjudicated formulary management system for review of restricted drug consults. A retrospective review of electronic medical records was conducted to identify restricted drug consults at this institution between January 1, 2014, and March 31, 2014. Only restricted drug consults that were not approved were included for evaluation in order to best characterize the effects of formulary interventions by pharmacists. Economic outcomes were determined as direct cost savings by comparing the cost of requested drug with the recommended drug and accounting for the cost of pharmacist review. Characteristics of consults that were not approved and pharmacist rationale were also evaluated. Of 1,802 restricted drug consults adjudicated by a pharmacist during the study period, 198 consults in 190 individual patients met criteria for inclusion and were evaluated. The most commonly requested indications were dyslipidemia, pain, and diabetes, while the most commonly requested drugs were rosuvastatin, insulin pens, tamsulosin, varenicline, ezetimibe, and rivaroxaban. The majority of consults were requested for outpatient use. Total cost savings among 195 evaluable consults was $420,324.05, while mean cost savings per consult was $2,229.43 (range: -$3,009.27-$65,982.36). The highest cost savings were seen with outpatient use. A pharmacist-adjudicated formulary consult service in a VA medical center was associated with a substantial cost savings after adjustment for cost of pharmacist review. Future research should assess clinical outcomes associated with a restrictive formulary management system. No outside funding supported this study. None of the authors report any financial interests or potential conflict of interest with regard to this work. Study concept and design were created by all authors. Data were collected and interpreted by Britt, with input from all authors. The manuscript was written by Britt and revised by all authors.

Current State of Antimicrobial Stewardship at Solid Organ and Hematopoietic Cell Transplant Centers in the United States.

OBJECTIVE To assess the extent of antimicrobial stewardship programs (ASPs) at solid organ transplant (SOT) and hematopoietic cell transplant (HCT) centers in the United States. DESIGN An 18-item voluntary survey was developed to gauge current antimicrobial stewardship practices in transplant patients, examine the availability and perceived usefulness of novel diagnostics and azole levels to guide therapy, and identify challenges for implementation of ASPs at these centers. PARTICIPANTS The survey was distributed electronically to infectious disease physicians and pharmacists at adult and pediatric SOT and HCT centers during May 1-22, 2015. Facilities were deidentified. RESULTS After duplicate removal, 71 (56%) of 127 unique transplant centers in 32 states were analyzed. Forty-four sites (62%) performed at least 100 SOT annually, and 40 (56%) performed at least 100 HCT annually. Top 5 stewardship activities encompassing transplant patients were formulary restriction, guideline development, prospective audit and feedback, education, and dose optimization. Respiratory viral panels (66/66 [100%]), azole levels (64/66 [97%]), and serum/bronchoalveolar lavage galactomannan (58/66 [88%]) were perceived as most useful to guide therapy. Apparent challenges to antimicrobial stewardship included undefined duration for certain infections (53/59 [90%]), diagnostic uncertainty (47/59 [80%]), the perception that antibiotic-resistant infections required escalation (42/59 [71%]), prescriber opposition (41/59 [69%]), and costly drugs (37/59 [63%]). CONCLUSIONS ASP activities were performed at many adult and pediatric SOT and HCT centers in the United States. Diagnostic and therapeutic uncertainty in transplant patients is challenging for ASPs. Collaborative research should examine the impact of antimicrobial stewardship practices in SOT and HCT. Infect Control Hosp Epidemiol 2016;1-6.

A Single-Payer System Can Save Primary Care

A Single-Payer System Can Save Primary Care

PRM24 - Feasibility of Linking Benefit Design and Administrative Claims Data to Evaluate the Impact of Medication Access and Restrictive Formularies Across Multiple Therapeutic Areas

PRM24 - Feasibility of Linking Benefit Design and Administrative Claims Data to Evaluate the Impact of Medication Access and Restrictive Formularies Across Multiple Therapeutic Areas

Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation.

The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials. Retrospective chart review before and after intervention. Le Bonheur Children's Hospital pediatric, neonatal, and cardiac ICUs. All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study. Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit-specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test. Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001). Guideline implementation was successful in reducing targeted broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.

Characteristics of Antimicrobial Stewardship Programs at Veterans Affairs Hospitals: Results of a Nationwide Survey.

BACKGROUND Antimicrobial stewardship programs (ASPs) are variably implemented. OBJECTIVE To characterize variations of antimicrobial stewardship structure and practices across all inpatient Veterans Affairs facilities in 2012 and correlate key characteristics with antimicrobial usage. DESIGN A web-based survey regarding stewardship activities was administered to each facility's designated contact. Bivariate associations between facility characteristics and inpatient antimicrobial use during 2012 were determined. SETTING Total of 130 Veterans Affairs facilities with inpatient services. RESULTS Of 130 responding facilities, 29 (22%) had a formal policy establishing an ASP, and 12 (9%) had an approved ASP business plan. Antimicrobial stewardship teams were present in 49 facilities (38%); 34 teams included a clinical pharmacist with formal infectious diseases (ID) training. Stewardship activities varied across facilities, including development of yearly antibiograms (122 [94%]), formulary restrictions (120 [92%]), stop orders for antimicrobial duration (98 [75%]), and written clinical pathways for specific conditions (96 [74%]). Decreased antimicrobial usage was associated with having at least 1 full-time ID physician (P=.03), an ID fellowship program (P=.003), and a clinical pharmacist with formal ID training (P=.006) as well as frequency of systematic patient-level reviews of antimicrobial use (P=.01) and having a policy to address antimicrobial use in the context of Clostridium difficile infection (P=.01). Stop orders for antimicrobial duration were associated with increased use (P=.03). CONCLUSIONS ASP-related activities varied considerably. Decreased antibiotic use appeared related to ID presence and certain select practices. Further statistical assessments may help optimize antimicrobial practices. Infect Control Hosp Epidemiol 2016;37:647-654.

Telephone Survey of Infection-Control and Antibiotic Stewardship Practices in Long-Term Care Facilities in Maryland

BackgroundMultidrug-resistant organisms are an emerging and serious threat to the care of patients. Long-term care facilities are considered a reservoir of these organisms partly because of the over-prescribing of antibiotics. Antibiotic use is common in long-term care facilities. Antibiotic stewardship programs have been shown to reduce antibiotic consumption in acute-care facilities. The purpose of our study is to investigate existing infection-control practices and antibiotic stewardship programs in long-term care facilities in Maryland. MethodsWe telephoned the infection-control personnel in 231 long-term care facilities in Maryland between February 2014 and July 2015 and reached 124 facilities (59%). ResultsAmong the 124 facilities surveyed, there were 14,371 beds and 337 infection-control personnel with basic infection-control training. Close to 20% of facilities use silver- or antimicrobial-impregnated urinary catheters. Most facilities (97%) track urinary tract infections. Although all report to the health department in the case of an outbreak, only 63 (50.8 %) report directly to the Centers for Disease Control and Prevention. About 80% of facilities isolate patients with Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci with acute infections only. Eighty percent of facilities have basic guidance on choice of antibiotic, and 27% have a restricted formulary. Only 25% of facilities have an antibiotic approval process. Thirty-five percent of facilities have training for antibiotics prescribing. However, 17% of facilities did not know whether such training existed. ConclusionsAntibiotic stewardship programs in long-term care facilities are still in early development stages, but our results demonstrate that the majority of facilities are collecting data on prescribing antibiotics, and a surprising number have antibiotic approval and antibiotics prescribing training.

Impact of a transition to more restrictive drug formulary on therapy discontinuation and medication adherence.

There is conclusive evidence demonstrating that formulary restrictions are associated with reduced utilization and pharmacy spending of the restricted drugs. However, prior efforts to implement restrictive formularies have been associated with inconsistent rates of therapy discontinuation and mixed impacts on adherence to therapy. Also, the impact of transferring patients from an already restrictive formulary to a more aggressive model has not been previously examined. This study evaluated the impact of implementation of a more restrictive formulary on therapy disruption, adherence rates, pharmacy costs and generic utilization among patients with common chronic conditions. In 2014, CVS Health implemented Value Formulary (VF), a restrictive benefit design with the aim of reducing spending while preserving access to and adherence to essential therapy, was used. A retrospective cohort study was conducted to assess changes in therapy disruption rates, pharmacy costs and generic dispensing rate (GDR) (for continuers) and medication adherence (for initiators) following the implementation of VF. The study group was selected from members of three existing employer clients transitioned from standard formulary (SF) to VF on January 2014. The control population was a matched group of six employers with the same preperiod formulary structure, business unit, adherence programmes and patient out-of-pocket cost as the study group. The control group retained SF in 2014. To assess therapy disruption after VF implementation, we categorized patients by their subsequent medication use into three groups: (i) therapy stopped, (ii) therapy continued and (iii) therapy switched. Medication adherence was measured as monthly proportion of days covered (PDC). Pharmacy cost and GDR were measured per utilizer per month (PUPM). Rates of therapy disruption in study and control groups were compared using the chi-square test. Differences in monthly PDC between matched groups were evaluated using multivariate linear regression. Impact of VF on pharmacy cost and GDR was measured through segmented regression of interrupted time series data with generalized estimating equations. A transition from SF to VF influenced drug coverage for approximately 13% of members (as their medications were either no longer covered, or covered restrictively under VF). Compared to patients whose plan sponsors retained SF, the patients that transitioned to VF had a modest (1·3%) but statistically significant increase in therapy discontinuation rates. This was offset by similarly modest improvements in adherence; patients who initiated therapy under VF demonstrated a 1·5% higher adherence to medications as compared to SF patients (P < 0·001). Medication costs in the VF group were lower by $20 PUPM (P < 0·001), and GDR was greater by 4·2% (P < 0·001). Transition of patients to a more restrictive drug formulary led to modest therapy discontinuation, similarly modest improvements in medication adherence and substantial prescription drug cost savings. As healthcare payors search for ways to control the rapid rise in spending for medications without compromising quality, the Value Formulary can serve as a useful tool.

A Review of Quality Measures for Assessing the Impact of Antimicrobial Stewardship Programs in Hospitals.

The growing problem of antimicrobial resistance (AMR) has led to calls for antimicrobial stewardship programs (ASP) to control antibiotic use in healthcare settings. Key strategies include prospective audit with feedback and intervention, and formulary restriction and preauthorization. Education, guidelines, clinical pathways, de-escalation, and intravenous to oral conversion are also part of some programs. Impact and quality of ASP can be assessed using process or outcome measures. Outcome measures are categorized as microbiological, patient or financial outcomes. The objective of this review was to provide an overview of quality measures for assessing ASP and the reported impact of ASP in peer-reviewed studies, focusing particularly on patient outcomes. A literature search of papers published in English between 1990 and June 2015 was conducted in five databases using a combination of search terms. Primary studies of any design were included. A total of 63 studies were included in this review. Four studies defined quality metrics for evaluating ASP. Twenty-one studies assessed the impact of ASP on antimicrobial utilization and cost, 25 studies evaluated impact on resistance patterns and/or rate of Clostridium difficile infection (CDI). Thirteen studies assessed impact on patient outcomes including mortality, length of stay (LOS) and readmission rates. Six of these 13 studies reported non-significant difference in mortality between pre- and post-ASP intervention, and five reported reductions in mortality rate. On LOS, six studies reported shorter LOS post intervention; a significant reduction was reported in one of these studies. Of note, this latter study reported significantly (p < 0.001) higher unplanned readmissions related to infections post-ASP. Patient outcomes need to be a key component of ASP evaluation. The choice of metrics is influenced by data and resource availability. Controlling for confounders must be considered in the design of evaluation studies to adequately capture the impact of ASP and it is important for unintended consequences to be considered. This review provides a starting point toward compiling standard outcome metrics for assessing ASP.

Antimicrobial stewardship in the intensive care setting--a review and critical appraisal of the literature.

Many antimicrobial stewardship programmes (ASPs) target the intensive care unit owing to high antimicrobial utilisation. In this review, we summarise and assess the quality of evidence supporting the implementation of various ASP strategies in the intensive care unit setting with a focus on publications between 2010 and 2015. We searched Medline up to April 2015 and screened publications of interest for additional relevant articles. We grouped the strategies into four categories: audit and feedback, formulary restrictions, guidelines/clinical pathways, and procalcitonin. We used GRADE terminology to describe the quality of evidence. We identified several studies reporting optimisation and reduction of antibiotic utilisation as well as cost reduction in all four strategies. Randomised controlled trials reviewing the role of procalcitonin demonstrate a moderate level of evidence. Given the lack of randomised controlled trials to support the role of guidelines, formulary restrictions, and audit and feedback, the level of evidence supporting these strategies is low. Importantly, there is no convincing evidence to support the main goal of ASP, namely to improve patient outcomes. Larger, rigorous long-term studies using a cluster randomised controlled trial or at least a controlled quasi-experimental design with time series are required to assess the impact of ASP on patient-important outcomes and on the emergence of resistance in the intensive care unit setting.

Confounding by drug formulary restriction in pharmacoepidemiologic research.

The potential consequences of confounding due to drug formulary restrictions in pharmacoepidemiologic research remain incompletely understood. Our objective was to illustrate this potential bias using the example of fluticasone/salmeterol combination therapy, an oral inhaler used to treat asthma and chronic obstructive pulmonary disease, whose use is restricted in the province of Quebec, Canada. We identified all new users of fluticasone/salmeterol in Quebec's administrative databases and classified those who received their initial dispensing of fluticasone/salmeterol between 1 September 1999 and 30 September 2003 as users from the liberal period and those who received it between 1 January 2004 and 31 October 2006 as users from the restricted period. The primary outcome was time to first hospitalization for respiratory causes within 12 months of cohort entry. Our cohort included 72 154 new users from the liberal period and 5058 from the restricted period. Compared with use during the liberal period, use during the restricted period was associated with an increased rate of hospitalization for respiratory causes (crude hazard ratio [HR] = 1.41, 95% confidence interval [CI] = 1.32, 1.51). Subsequent adjustment for age, sex, and hospitalization for respiratory causes in the previous year attenuated the association (HR = 1.05, 95%CI = 0.98, 1.12). Further adjustment for other potential confounders resulted in a lower rate during the restricted period (HR = 0.78, 95%CI = 0.73, 0.83). Formulary restrictions can result in substantial and unexpected confounding and should be considered during the design and analysis of pharmacoepidemiologic studies.