Systematic reviews of complex interventions can vary widely in purpose, data availability and heterogeneity, and stakeholder expectations.
This article addresses the uncertainty that systematic ...reviewers face in selecting methods for reviews of complex interventions. Specifically, it lays out parameters for systematic reviewers to consider when selecting analytic approaches that best answer the questions at hand and suggests analytic techniques that may be appropriate in different circumstances.
Systematic reviews of complex interventions comprising multiple questions may use multiple analytic approaches. Parameters to consider when choosing analytic methods for complex interventions include nature and timing of the decision (clinical practice guideline, policy, or other); purpose of the review; extent of existing evidence; logistic factors such as the timeline, process, and resources for deciding the scope of the review; and value of information to be obtained from choosing specific systematic review methods. Reviewers may elect to revise their analytic approach based on new or changing considerations during the course of the review but should guard against bias through transparency of reporting.
Objective
Neuropathic pain is generally chronic and challenging to treat. Studies often ignore chronicity by reporting short‐duration outcomes and fail to account for medication tolerability. We ...assessed efficacy of oral medications on chronic peripheral neuropathic pain.
Methods
Relevant published, English‐language, randomized controlled trials administering oral medications for peripheral neuropathic pain were identified through MEDLINE (1966 to Dec 1, 2012), EMBASE (1980 to December 2012), the Cochrane Library Databases (through December 2012), and the Oxford Pain Relief Database (through 2012). Included studies reported end point pain or pain reduction from baseline on an 11‐point scale (0–10); had active treatment ≥ 12 weeks; reported an intention‐to‐treat analysis, and had 5‐point quality score ≥ 3. ed information included patient characteristics, neuropathic pain condition, drug and dosage arms, adverse events rates causing dropout, and secondary measures (50% pain improvement, global improvement, and sleep interference). Primary outcome meta‐analysis, stratified by drug and dosage, was followed by an indirect treatment comparison adjusting for study dropouts due to adverse events.
Results
Seventeen studies comprised of 5,975 subjects, totaling 38 active trial arms evaluating 7 drugs, and 17 drug‐dosing combinations met inclusion criteria. Mean pain reduction over placebo ranked highest for duloxetine 120 mg (1.17 95% CI 0.77, 1.58) and pregabalin 600 mg (1.11 95% CI 0.77, 1.45). The Indirect treatment comparison showed largest effect size for duloxetine at 120 and 60 mg followed by pregabalin 600 mg.
Conclusions
Pregabalin and duloxetine had the largest beneficial effects for chronic peripheral neuropathic pain. In the absence of head‐to‐head trials, meta‐analysis and indirect treatment comparisons inform best practice clinical decision‐making.
Abstract Background Computerized provider order entry (CPOE) is the process of entering physician orders directly into an electronic health record. Although CPOE has been shown to improve medication ...safety and reduce health care costs, these improvements have been demonstrated largely in the inpatient setting; the cost-effectiveness in the ambulatory setting remains uncertain. Objective The objective was to estimate the cost-effectiveness of CPOE in reducing medication errors and adverse drug events (ADEs) in the ambulatory setting. Methods We created a decision-analytic model to estimate the cost-effectiveness of CPOE in a midsized (400 providers) multidisciplinary medical group over a 5-year time horizon— 2010 to 2014—the time frame during which health systems are implementing CPOE to meet Meaningful Use criteria. We adopted the medical group’s perspective and utilized their costs, changes in efficiency, and actual number of medication errors and ADEs. One-way and probabilistic sensitivity analyses were conducted. Scenario analyses were explored. Results In the base case, CPOE dominated paper prescribing, that is, CPOE cost $18 million less than paper prescribing, and was associated with 1.5 million and 14,500 fewer medication errors and ADEs, respectively, over 5 years. In the scenario that reflected a practice group of five providers, CPOE cost $265,000 less than paper prescribing, was associated with 3875 and 39 fewer medication errors and ADEs, respectively, over 5 years, and was dominant in 80% of the simulations. Conclusions Our model suggests that the adoption of CPOE in the ambulatory setting provides excellent value for the investment, and is a cost-effective strategy to improve medication safety over a wide range of practice sizes.
Background
Migraine prevention guidelines recommend oral prophylactic medications for patients with frequent headache. This study examined oral migraine preventive medication (OMPM) treatment ...patterns by evaluating medication persistence, switching, and re-initiation in patients with chronic migraine (CM).
Methods
A retrospective US claims analysis (Truven Health MarketScan® Databases) evaluated patients ≥18 years old diagnosed with CM who had initiated an OMPM between 1 January, 2008 and 30 September, 2012. Treatment persistence was measured at six and 12 months’ follow-up. Time-to-discontinuation was assessed for each OMPM and compared using Cox regression models. Among those who discontinued, the proportion that switched OMPMs within 60 days or re-initiated treatment between 61 to 365 days, and their associated persistence rates, were also assessed.
Results
A total of 8707 patients met the inclusion/exclusion criteria. Persistence to the initial OMPM was 25% at six months and 14% at 12 months. Based on Kaplan-Meier curves, a sharp decline of patients discontinuing was observed by 30 days, and approximately half discontinued by 60 days. Similar trends in time-to-discontinuation were seen following the second or third OMPM. Amitriptyline, gabapentin, and nortriptyline had significantly higher likelihood of non-persistence compared with topiramate. Among patients who discontinued, 23% switched to another prophylactic and 41% re-initiated therapy within one year. Among patients who switched, persistence was between 10 to 13% and among re-initiated patients, persistence was between 4 to 8% at 12 months.
Conclusions
Persistence to OMPMs is poor at six months and declines further by 12 months. Switching between OMPMs is common, but results indicate that persistence worsens as patients cycle through various OMPMs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sleep dysfunction can manifest in several ways, ranging from insomnia to somnolence, and from disrupted sleep to lack of restful sleep. Measuring sleep dysfunction is an area of active research and ...there exist a number of patient-reported outcome instruments that measure various aspects of sleep dysfunction. However, these instruments have not been evaluated systematically. We used a conceptual model of sleep that included four physical domains of general interest to patients and investigators, and cover the breadth of this disorder: sleep initiation; sleep maintenance; sleep adequacy; and somnolence. We next considered the additional health-related quality-of-life (HR-QOL) domains of psychological and social functioning, progressing along the continuum to include health perceptions and opportunity. We then conducted a literature review to identify instruments and, using criteria developed by the Medical Outcomes Trust Scientific Advisory Committee, evaluated these instruments for their potential use in measuring sleep dysfunction. Twenty-two instruments were identified. Six instruments were found to include the four physical domains defined a priori (Basic Nordic Sleep Questionnaire, Leeds Sleep Evaluation Questionnaire, Medical Outcomes Study - Sleep Problems Measures, Pittsburgh Sleep Diary, Pittsburgh Sleep Quality Index, Self-Rated Sleep Questionnaire and the Sleep Dissatisfaction Questionnaire). Several additional instruments addressed at least some of the domains and thus may be useful for specific purposes. A few instruments addressed overall HR-QOL, but did not include all four domains of interest (Functional Outcomes of Sleep Questionnaire, Quality of Life in Insomniacs and the Sleep-Wake Activity Inventory). Two instruments had undergone extensive psychometric evaluation (Medical Outcomes Study - Sleep Problems Measures and Pittsburgh Sleep Quality Index), with only the latter reporting information about interpretability. Our review indicates that measuring sleep dysfunction in adults is an area of active research and that much work still needs to be completed, specifically the study of interpretability and the application of patient preferences or item response theory. The specific research focus should dictate instrument selection.
Abstract
Context
Diabetic kidney disease affects nearly one-third of US adults with prevalent type 2 diabetes mellitus (T2DM). The use of new antidiabetic medications in the prevention and treatment ...of diabetic kidney disease is a growing area of research interest.
Objective
We sought to characterize the risk of developing a composite kidney outcome among patients receiving a new antidiabetic medication of the SGLT-2i, GLP-1ra, and DPP-4i drug classes.
Methods
We conducted a systematic literature search in MEDLINE to identify randomized trials observing kidney safety endpoints associated with the use of new antidiabetic medications. Two independent reviewers selected the 7 eligible studies for analysis. Included studies were published between January 2013 and March 2020, conducted with adult participantss, published full-text in English, and observed composite kidney outcomes. A network meta-analysis was conducted within a Bayesian framework using a fixed-effects model with uninformative priors.
Results
A qualitative assessment of transitivity was conducted to ensure similar distribution of potential modifiers across studies. Included studies were generally comparable in mean age, glycated hemoglobin A1c (HbA1c), and mean duration of T2DM at baseline.
Main Conclusions
Compared with placebo, dapagliflozin was associated with the greatest reduction in risk of developing the composite kidney outcome (hazard ratio 0.53; 95% credible interval, 0.43-0.66) followed by empagliflozin, canagliflozin, semaglutide, and liraglutide. Linagliptin did not show a significant reduction in risk of the outcome.
Limitations
This analysis was limited by the scarcity of data for kidney safety endpoints in large, randomized clinical trials. Although the heterogeneity statistic was low, there are slight differences in study design and baseline demographic characteristics across trials.
Background
Adherence and persistence to therapy, or how well a patient follows provider directions on frequency and time to discontinuation of prescribed medications, is associated with positive ...health outcomes, including decreased healthcare costs and patient mortality. A clear literature gap exists assessing adherence and persistence to antidepressants (ADs) in the major depressive disorder (MDD) population at clinically relevant time points and at the therapeutic class level.
Objective
This study assessed adherence and persistence to specific ADs, therapeutic classes, and AD therapy overall at multiple time points among US individuals from commercial, Medicare supplemental, and Medicaid insurance plans.
Methods
Patients with MDD without AD or MDD claims in the prior 6 months who initiated therapy in 2003–2014 with a selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic AD (TCA), monoamine oxidase inhibitor (MAOI), or other AD were identified using MarketScan
®
databases. These databases contain information on diagnoses, billing codes, and dates of service. Adherence (proportion of days covered) and persistence (days until a 30-day gap in therapy) were calculated to AD medication, AD therapeutic class, and AD therapy overall over the first 3, 6, 9, and 12 months from the index prescription date. Multivariable logistic regression estimated the adjusted odds ratios (ORs) of adherence to initial AD medication comparing AD therapeutic classes.
Results
For 527,907 patients, adherence to initial AD medication decreased over 3, 6, 9, and 12 months (41, 31, 24, and 21%, respectively). Similar patterns were observed for adherence to initial AD therapeutic class, AD therapy overall, and all three persistence calculations. The odds of adherence to SNRIs versus SSRIs were 20–27% greater at 3, 6, 9, and 12 months (ORs 1.20, 1.23, 1.25, 1.27, respectively;
p
-values all <0.0001). Similar or significantly lower odds of adherence were demonstrated for other classes versus SSRIs at 3, 6, 9, and 12 months ORs for other ADs 0.80, 0.77, 0.74, 0.72, respectively (
p
-values all <0.0001); ORs for TCAs 0.46, 0.45, 0.47, 0.49, respectively (
p
-values all <0.0001); ORs for MAOIs 1.13, 1.0, 0.77, 0.69, respectively (
p
-values all >0.05).
Conclusion
We found low adherence and persistence to ADs in the MDD population. Within the limitations of the insurance claims data we analysed, our results suggest that adherence may differ based on therapeutic class, as patients initiating SNRI therapy appeared to have a higher likelihood of adherence versus SSRIs over the year assessed, while the odds of adherence appeared similar or lower for other classes versus SSRIs. Further prospective research is needed to confirm these findings and determine additional drivers of these apparent differences by AD therapeutic class.
Interstitial cystitis (IC) is a debilitating condition that affects up to 5% of the U.S.
This condition is characterized by bladder pain, urinary urgency and frequency, nocturia, and, in some ...patients, bladder lesions called Hunner's lesions (HL). IC patients who have HL experience a clinical course that is distinct from those without HL and, as a result, respond differently to existing treatments. Without effective and lasting therapeutic options, IC patients are expected to experience a reduced quality of life and be a significant economic burden. Previous research describing the burden of IC is not only outdated but lacks stratification by HL.
To (a) characterize health care utilization, direct costs, and comorbidities associated with IC and (b) elucidate differences between patients with and without HL.
A retrospective analysis was conducted using health care claims from the Truven Health MarketScan Research Databases. Adults with an incident IC diagnosis between 2009 and 2014 were identified and matched 1:4 to non-IC patients on age, gender, and geographic region. Health care utilization, direct costs, and comorbidities during the first 12 months after diagnosis were compared between the 2 groups, as well as between IC subgroups with and without HL. Associations were evaluated after adjustment for potential confounders using regression models.
A total of 24,836 IC patients were identified and matched to 99,344 non-IC patients. Patients were predominantly female (92%), with a mean age of 49.0 (SD = 15.3) years. IC patients used significantly more health care resources across all categories compared with non-IC patients. On average, having IC was associated with $7,223 higher total health care costs than not having IC (95% CI = $6,650-$7,796), with outpatient costs contributing to 71% of the difference, after adjusting for baseline age, gender, region, insurance type, plan type, and Charlson Comorbidity Index (CCI) score. The odds of developing select comorbidities were 2.61 times greater in IC patients compared with non-IC patients (95% CI = 2.52-2.70), adjusting for baseline age, sex, region, and CCI score. Among IC patients, the HL subgroup (n = 292) used more health care resources, and having HL was associated with $6,895 higher total health care costs compared with not having HL (95% CI = $3,770-$10,020) after adjusting for baseline age, gender, region, insurance type, and plan type.
Findings suggest that patients with IC have significantly higher health care utilization, costs, and comorbidities compared with non-IC patients. This economic burden is further amplified in those with HL.
Funding for this study was contributed by Allergan. Tung was supported by a training grant from Allergan at the time of this study. Hepp was an Allergan employee at the time this study was conducted. The other authors have nothing to disclose. This research was previously presented, in part, as a poster presentation at the International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; Washington, DC; May 23, 2016. Study concept and design were primarily contributed by Hepp, along with Tung and Devine. Tung took the lead in data collection, with assistance from Hepp, and data interpretation was performed by Tung, along with Bansal and Devine. The manuscript was prepared primarily by Tung, along with Devine, Bansal, and Hepp.
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