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Advances in science have led to the development of multiple biologics and small molecules for the treatment of inflammatory bowel diseases (IBDs). This growth in advanced medical therapies has been accompanied by an increase in methodological innovation to study and compare therapies. Guidelines provide an evidence-based approach to integrating therapies into routine practice, but they are often unable to provide timely recommendations as new therapies come to market, and they have limited incorporation of real-world evidence when making recommendations. This limits the scope and usability of guidelines, and a gap remains in defining how best to position and integrate advanced medical therapies for IBD. In this review, we provide a framework for clinicians and researchers to understand key differences in sources of evidence, how different methodologies are applied to study the comparative effectiveness of advanced medical therapies in IBD, and considerations for how these sources of evidence can be used to better integrate current guideline recommendations. Over time, we anticipate this framework will allow for a transition to living guidelines and/or practice recommendations.
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Humanos , Productos Biológicos/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factores BiológicosRESUMEN
Comparing different medications is complicated when adherence to these medications differs. We can overcome the adherence issue by assessing effectiveness under sustained use, as in usual causal 'per-protocol' estimands. However, when sustained use is challenging to satisfy in practice, the usefulness of these estimands can be limited. Here we propose a different class of estimands: separable effects for adherence. These estimands compare modified medications, holding fixed a component responsible for non-adherence. Under assumptions about treatment components' mechanisms of effect, a separable effects estimand can quantify the effectiveness of medication initiation strategies on an outcome of interest under the adherence mechanism of one of the medications. These assumptions are amenable to interrogation by subject-matter experts and can be evaluated using causal graphs. We describe an algorithm for constructing causal graphs for separable effects, illustrate how these graphs can be used to reason about assumptions required for identification, and provide semi-parametric weighted estimators.
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Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility of broad clinical deployment has not been established. The objective of this study was to implement RPM based on rWGS and evaluate the clinical and economic impact of this implementation as a first line diagnostic test in the California Medicaid (Medi-Cal) program. Project Baby Bear was a payor funded, prospective, real-world quality improvement project in the regional ICUs of five tertiary care children's hospitals. Participation was limited to acutely ill Medi-Cal beneficiaries who were admitted November 2018 to May 2020, were <1 year old and within one week of hospitalization, or had just developed an abnormal response to therapy. The whole cohort received RPM. There were two prespecified primary outcomes-changes in medical care reported by physicians and changes in the cost of care. The majority of infants were from underserved populations. Of 184 infants enrolled, 74 (40%) received a diagnosis by rWGS that explained their admission in a median time of 3 days. In 58 (32%) affected individuals, rWGS led to changes in medical care. Testing and precision medicine cost $1.7 million and led to $2.2-2.9 million cost savings. rWGS-based RPM had clinical utility and reduced net health care expenditures for infants in regional ICUs. rWGS should be considered early in ICU admission when the underlying etiology is unclear.
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Enfermedad Crítica/terapia , Medicina de Precisión , Secuenciación Completa del Genoma , California , Estudios de Cohortes , Costo de Enfermedad , Cuidados Críticos , Femenino , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Masculino , Medicaid , Estudios Prospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
A crossover trial is an efficient trial design when there is no carry-over effect. To reduce the impact of the biological carry-over effect, a washout period is often designed. However, the carry-over effect remains an outstanding concern when a washout period is unethical or cannot sufficiently diminish the impact of the carry-over effect. The latter can occur in comparative effectiveness research, where the carry-over effect is often non-biological but behavioral. In this paper, we investigate the crossover design under a potential outcomes framework with and without the carry-over effect. We find that when the carry-over effect exists and satisfies a sign condition, the basic estimator underestimates the treatment effect, which does not inflate the type I error of one-sided tests but negatively impacts the power. This leads to a power trade-off between the crossover design and the parallel-group design, and we derive the condition under which the crossover design does not lead to type I error inflation and is still more powerful than the parallel-group design. We also develop covariate adjustment methods for crossover trials. We evaluate the performance of cross-over design and covariate adjustment using data from the MTN-034/REACH study.
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Proyectos de Investigación , Estudios CruzadosRESUMEN
Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.
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Síndrome del Colon Irritable , Estimulación Eléctrica Transcutánea del Nervio , Adolescente , Humanos , Dolor Abdominal/terapia , Dolor Abdominal/complicaciones , Análisis Costo-Beneficio , Atención a la Salud , Síndrome del Colon Irritable/complicaciones , Ensayos Clínicos Controlados como AsuntoRESUMEN
BACKGROUND: Comparative effectiveness research is meant to determine which commonly employed medical interventions are most beneficial, least harmful, and/or most costly in a real-world setting. While the objectives for comparative effectiveness research are clear, the field has failed to develop either a uniform definition of comparative effectiveness research or an appropriate set of recommendations to provide standards for the design of critical care comparative effectiveness research trials, spurring controversy in recent years. The insertion of non-representative control and/or comparator arm subjects into critical care comparative effectiveness research trials can threaten trial subjects' safety. Nonetheless, the broader scientific community does not always appreciate the importance of defining and maintaining critical care practices during a trial, especially when vulnerable, critically ill populations are studied. Consequently, critical care comparative effectiveness research trials sometimes lack properly constructed control or active comparator arms altogether and/or suffer from the inclusion of "unusual critical care" that may adversely affect groups enrolled in one or more arms. This oversight has led to critical care comparative effectiveness research trial designs that impair informed consent, confound interpretation of trial results, and increase the risk of harm for trial participants. METHODS/EXAMPLES: We propose a novel approach to performing critical care comparative effectiveness research trials that mandates the documentation of critical care practices prior to trial initiation. We also classify the most common types of critical care comparative effectiveness research trials, as well as the most frequent errors in trial design. We present examples of these design flaws drawn from past and recently published trials as well as examples of trials that avoided those errors. Finally, we summarize strategies employed successfully in well-designed trials, in hopes of suggesting a comprehensive standard for the field. CONCLUSION: Flawed critical care comparative effectiveness research trial designs can lead to unsound trial conclusions, compromise informed consent, and increase risks to research subjects, undermining the major goal of comparative effectiveness research: to inform current practice. Well-constructed control and comparator arms comprise indispensable elements of critical care comparative effectiveness research trials, key to improving the trials' safety and to generating trial results likely to improve patient outcomes in clinical practice.
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Brazo , Investigación sobre la Eficacia Comparativa , Humanos , Consentimiento Informado , Sujetos de Investigación , Cuidados CríticosRESUMEN
In a prospective observational study (POS) designed to assess the average causal effect of a treatment (e.g. Drug A) compared to a comparator (e.g. Drug B) in the treatment population, enrolling all patients who are assigned to the treatments of interest for follow-up has a potentially large negative impact on the statistical efficiency and bias of the analysis of the outcomes and on the cost of the study. "Up-front matching" is an innovative enrollment method for selecting patients for long-term follow-up among those who have already been assigned to treatment or comparator which uses frequency matching and hence avoids the restrictions of individual matching that other methods have used. To achieve potential statistical and logistical efficiencies in the POS, in up-front matching, a target population is defined based on a retrospective database which then enables selecting populations of patients for follow-up that have desirable statistical properties. In particular, the resulting populations of patients who are enrolled look like the population of treatment patients were randomized to treatment or comparator for the baseline covariates that are used to select patients for follow-up. The method is illustrated in detail for a study designed to assess the effect of injectable antipsychotics versus oral antipsychotics.
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BACKGROUND: The ability to do comparative effectiveness research (CER) for proximal humerus fractures (PHF) using data in electronic health record (EHR) systems and administrative claims databases was enhanced by the 10th revision of the International Classification of Diseases (ICD-10), which expanded the diagnosis codes for PHF to describe fracture complexity including displacement and the number of fracture parts. However, these expanded codes only enhance secondary use of data for research if the codes selected and recorded correctly reflect the fracture complexity. The objective of this project was to assess the accuracy of ICD-10 diagnosis codes documented during routine clinical practice for secondary use of EHR data. METHODS: A sample of patients with PHFs treated by orthopedic providers across a large, regional health care system between January 1, 2016, and December 31, 2018, were retrospectively identified from the EHR. Four fellowship-trained orthopedic surgeons reviewed patient radiographs and recorded the Neer Classification characteristics of displacement, number of parts, and fracture location(s). The fracture characteristics were then reviewed by a trained coder, and the most clinically appropriate ICD-10 diagnosis code based on the number of fracture parts was assigned. We assessed congruence between ICD-10 codes documented in the EHR and radiograph-validated codes, and assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EHR-documented ICD-10 codes. RESULTS: There were 761 patients with unilateral, closed PHF who met study inclusion criteria. On average, patients were 67 years of age and 77% were female. Based on radiograph review, 37% were 1-part fractures, 42% were 2-part, 11% were 3-part, and 10% were 4-part fractures. Of the EHR diagnosis codes recorded during clinical practice, 59% were "unspecified" fracture diagnosis codes that did not identify the number of fracture parts. Examination of fracture codes revealed PPV was highest for 1-part (PPV = 0.66, 95% confidence interval [CI] 0.60-0.72) and 4-part fractures (PPV = 0.67, 95% CI 0.13-1.00). CONCLUSIONS: Current diagnosis coding practices do not adequately capture the fracture complexity needed to conduct subgroup analysis for PHF. Conclusions drawn from population studies or large databases using ICD-10 codes for PHF classification should be interpreted within this limitation. Future studies are warranted to improve diagnostic coding to support large observational studies using EHR and administrative claims data.
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Fracturas del Húmero , Clasificación Internacional de Enfermedades , Femenino , Humanos , Masculino , Bases de Datos Factuales , Registros Electrónicos de Salud , Reproducibilidad de los Resultados , Estudios Retrospectivos , AncianoRESUMEN
BACKGROUND: Immunocompromised patients are at high risk of severe coronavirus disease 2019 (COVID-19) and death, yet treatment strategies for immunocompromised patients hospitalized for COVID-19 reflect variations in clinical practice. In this comparative effectiveness study, we investigated the effect of remdesivir treatment on inpatient mortality among immunocompromised patients hospitalized for COVID-19 across all variants of concern (VOC) periods. METHODS: Data for immunocompromised patients hospitalized for COVID-19 between December 2020 and April 2022 were extracted from the US PINC AITM Healthcare Database. Patients who received remdesivir within 2 days of hospitalization were matched 1:1 using propensity score matching to patients who did not receive remdesivir. Additional matching criteria included admission month, age group, and hospital. Cox proportional hazards models were used to examine the effect of remdesivir on risk of 14- and 28-day mortality during VOC periods. RESULTS: A total of 19 184 remdesivir patients were matched to 11 213 non-remdesivir patients. Overall, 11.1% and 17.7% of remdesivir patients died within 14 and 28 days, respectively, compared with 15.4% and 22.4% of non-remdesivir patients. Remdesivir was associated with a reduction in mortality at 14 (hazard ratio [HR], 0.70; 95% confidence interval, .62-.78) and 28 days (HR, 0.75; 95% CI, .68-.83). The survival benefit remained significant during the pre-Delta, Delta, and Omicron periods. CONCLUSIONS: Prompt initiation of remdesivir in immunocompromised patients hospitalized for COVID-19 is associated with significant survival benefit across all variant waves. These findings provide much-needed evidence relating to the effectiveness of a foundational treatment for hospitalized COVID-19 patients among a high-risk population.
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COVID-19 , Humanos , Tratamiento Farmacológico de COVID-19 , Huésped Inmunocomprometido , Pacientes Internos , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Recent trials testing immune-checkpoint inhibitors in esophago-gastric malignancies have shown mixed results. We aim to assess key subgroups using the ASCO Net Health Benefit Score (NHBS) and ESMO Magnitude of Clinical Benefit Scale (MCBS). MATERIALS AND METHODS: A search for phase III trials of FDA-approved anti-PD-1 or anti-PD-L1 drugs in esophago-gastric cancer trials was identified using www.clinicaltrials.gov. These published studies were scored using the ASCO NHBS and ESMO MCBS. The ASCO NHBS scores were compared by primary site of cancer (esophageal vs gastric) and PD-L1 expression using the Mann-Whitney test and the ESMO-MCBS grading, by Fisher's Exact test. RESULTS: Fifteen of 45 clinical trials were included. Of them, 6 were primarily esophageal cancer trials, and 9 were primarily gastric cancer trials. Ten stratified their analysis based on PD-L1 expression. The ASCO NHBS score was higher (mean 40, range 20 to 56.6 vs. mean 12, range -1.1 to 18.4, P < .01) for esophageal cancer than gastric cancer. No difference was observed in survival and response endpoints between the 2 groups. Similarly, the ESMO MCBS scored higher for esophageal cancer group than gastric cancer (P < .05). Additionally, the scores were higher in those with high PD-L1 expression vs. low PD-L1 (mean 36, range 11.2-66.6 vs. mean 14, range -19.5 to 43.6, P < .05). CONCLUSION: The ASCO NHB and ESMO scores were consistently higher among esophageal cancer trials than gastric cancer trials and in those with high PD-L1 expression than low expression. Histology and PD-L1 expression should be considered when discussing value of immunotherapy to patients.
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Neoplasias Esofágicas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Ensayos Clínicos Fase III como AsuntoRESUMEN
BACKGROUND & AIMS: Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. METHODS: We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. RESULTS: From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. CONCLUSIONS: Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.
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Dispepsia , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Dispepsia/diagnóstico , Dispepsia/tratamiento farmacológico , Análisis Costo-Beneficio , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Endoscopía Gastrointestinal , Satisfacción del PacienteRESUMEN
OBJECTIVE: The IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib. MATERIAL AND METHODS: A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). RESULTS: For ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs. CONCLUSIONS: Guselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs.
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Artritis Psoriásica , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Metaanálisis en Red , Teorema de Bayes , Resultado del Tratamiento , Psoriasis/tratamiento farmacológico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: There is a relative lack of comparative effectiveness research on revascularization for patients with chronic limb-threatening ischemia (CLTI). We examined the association between lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) for CLTI and 30-day and 5-year all-cause mortality and 30-day and 5-year amputation. METHODS: Patients undergoing LEB and PVI of the below-the-knee popliteal and infrapopliteal arteries between 2014 and 2019 were queried from the Vascular Quality Initiative, and outcomes data were obtained from the Medicare claims-linked Vascular Implant Surveillance and Interventional Outcomes Network database. Propensity scores were calculated on 15 variables using a logistic regression model to control for imbalances between treatment groups. A 1:1 matching method was used. Kaplan-Meier survival curves and hierarchical Cox proportional hazards regression with a random intercept for site and operator nested in site to account for clustered data compared 30-day and 5-year all-cause mortality between groups. Thirty-day and 5-year amputation were subsequently compared using competing risk analysis to account for the competing risk of death. RESULTS: There was a total of 2075 patients in each group. The overall mean age was 71 ± 11 years, 69% were male, and 76% were white, 18% were black, and 6% were of Hispanic ethnicity. Baseline clinical and demographic characteristics in the matched cohort were balanced between groups. There was no association between all-cause mortality over 30 days and LEB vs PVI (cumulative incidence, 2.3% vs 2.3% by Kaplan Meier; log-rank P-value = .906; hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.44; P-value = .80). All-cause mortality over 5 years was lower for LEB vs PVI (cumulative incidence, 55.9% vs 60.1% by Kaplan Meier; log-rank P-value < .001; HR, 0.77; 95% CI, 0.70-0.86; P-value < .001). Accounting for competing risk of death, amputation over 30 days was also lower in LEB vs PVI (cumulative incidence function, 1.9% vs 3.0%; Fine and Gray P-value = .025; subHR, 0.63; 95% CI, 0.42-0.95; P-value = .025). There was no association between amputation over 5 years and LEB vs PVI (cumulative incidence function, 22.6% vs 23.4%; Fine and Gray P-value = .184; subHR, 0.91; 95% CI, 0.79-1.05; P-value = .184). CONCLUSIONS: In the Vascular Quality Initiative-linked Medicare registry, LEB vs PVI for CLTI was associated with a lower risk of 30-day amputation and 5-year all-cause mortality. These results will serve as a foundation to validate recently published randomized controlled trial data, and to broaden the comparative effectiveness evidence base for CLTI.
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Procedimientos Endovasculares , Enfermedad Arterial Periférica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Crónica que Amenaza las Extremidades , Procedimientos Endovasculares/efectos adversos , Isquemia/diagnóstico , Isquemia/cirugía , Recuperación del Miembro , Extremidad Inferior/irrigación sanguínea , Medicare , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Estados Unidos/epidemiología , Investigación sobre la Eficacia ComparativaRESUMEN
BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Trastornos de Tic , Humanos , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Depresión/tratamiento farmacológico , Depresión/epidemiología , Estudios de Cohortes , Escitalopram , Fluoxetina/efectos adversos , Metilfenidato/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversosRESUMEN
Comparative effectiveness research is often concerned with evaluating treatment strategies sustained over time, that is, time-varying treatments. Inverse probability weighting (IPW) is often used to address the time-varying confounding by re-weighting the sample according to the probability of treatment receipt at each time point. IPW can also be used to address any missing data by re-weighting individuals according to the probability of observing the data. The combination of these two distinct sets of weights may lead to inefficient estimates of treatment effects due to potentially highly variable total weights. Alternatively, multiple imputation (MI) can be used to address the missing data by replacing each missing observation with a set of plausible values drawn from the posterior predictive distribution of the missing data given the observed data. Recent studies have compared IPW and MI for addressing the missing data in the evaluation of time-varying treatments, but they focused on missing confounders and monotone missing data patterns. This article assesses the relative advantages of MI and IPW to address missing data in both outcomes and confounders measured over time, and across monotone and non-monotone missing data settings. Through a comprehensive simulation study, we find that MI consistently provided low bias and more precise estimates compared to IPW across a wide range of scenarios. We illustrate the implications of method choice in an evaluation of biologic drugs for patients with severe rheumatoid arthritis, using the US National Databank for Rheumatic Diseases, in which 25% of participants had missing health outcomes or time-varying confounders.
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Investigación sobre la Eficacia Comparativa , Humanos , Probabilidad , Sesgo , Simulación por ComputadorRESUMEN
Whilst the Randomised Controlled Trial remains the gold standard for deriving robust causal estimates of treatment efficacy, too often a traditional design proves prohibitively expensive or cumbersome when it comes to assessing questions regarding the comparative effectiveness of routinely used treatments. As a result, patients experience variation in practice as clinicians lack the evidence needed to personalise treatments effectively. This variation may be classified as unwarranted, where existing evidence is ignored, or legitimate where in the absence of evidence, clinicians rely on experience, expert opinion, and inferred principles from basic science to make decisions. We argue that within the right ethical and technological framework, legitimate variation can be transformed into a mechanism for evidence generation and learning. Learning Health Systems which harness existing variation in practice, represent a novel approach for generating evidence from everyday clinical practice. The development of these systems has gained traction due to the increased availability of modern Electronic Health Record Systems. However, despite their promise, overcoming hurdles to successfully integrating clinical trials within Learning Health Systems has proven challenging. This article describes the origins of integrated clinical trials and explores two main barriers to their further implementation - how best to obtain informed consent from patients to participate in routine comparative effectiveness research, and how to automate and integrate randomisation into a clinical workflow. Having described these barriers, we present a potential solution in the form of a research pipeline using a novel form of flexible point-of-care randomisation to allow clinicians and patients to participate in studies where there is clinical equipoise.
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Registros Electrónicos de Salud , Sistemas de Atención de Punto , Humanos , Proyectos de Investigación , Aprendizaje , Consentimiento InformadoRESUMEN
Large randomised trials provide the most reliable evidence of effectiveness of new treatments in clinical practice. However, the time and resources required to complete such trials can be daunting. An overarching clinical trial platform focused on a single condition or type of surgery, aiming to compare several treatments, with an option to stop any or add in new treatment options, can provide greater efficiency. This has the potential to accelerate knowledge acquisition and identify effective, ineffective, or harmful treatments faster. The master protocol of the platform defines the study population(s) and standardised procedures. Ineffective or harmful treatments can be discarded or study drug dose modified during the life cycle of the trial. Other adaptive elements that can be modified include eligibility criteria, required sample size for any comparison(s), randomisation assignment ratio, and the addition of other promising treatment options. There are excellent opportunities for anaesthetists to establish platform trials in perioperative medicine. Platform trials are highly efficient, with the potential to provide quicker answers to important clinical questions that lead to improved patient care.
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Anestesia , Anestesiología , Medicina Perioperatoria , Humanos , Proyectos de InvestigaciónRESUMEN
OBJECTIVE: Provide proof-of-concept for development of a Pediatric Functional Status eScore (PFSeS). Demonstrate that expert clinicians rank billing codes as relevant to patient functional status and identify the domains that codes inform in a way that reliably matches analytical modeling. DESIGN: Retrospective chart review, modified Delphi, and nominal group techniques. SETTING: Large, urban, quaternary care children's hospital in the Midwestern United States. PARTICIPANTS: Data from 1955 unique patients and 2029 hospital admissions (2000-2020); 12 expert consultants representing the continuum of rehabilitation care reviewed 2893 codes (procedural, diagnostic, pharmaceutical, durable medical equipment). MAIN OUTCOME MEASURES: Consensus voting to determine whether codes were associated with functional status at discharge and, if so, what domains they informed (self-care, mobility, cognition/ communication). RESULTS: The top 250 and 500 codes identified by statistical modeling were mostly composed of codes selected by the consultant panel (78%-80% of the top 250 and 71%-78% of the top 500). The results provide evidence that clinical experts' selection of functionally meaningful codes corresponds with codes selected by statistical modeling as most strongly associated with WeeFIM domain scores. The top 5 codes most strongly related to functional independence ratings from a domain-specific assessment indicate clinically sensible relationships, further supporting the use of billing data in modeling to create a PFSeS. CONCLUSIONS: Development of a PFSeS that is predicated on billing data would improve researchers' ability to assess the functional status of children who receive inpatient rehabilitation care for a neurologic injury or illness. An expert clinician panel, representing the spectrum of medical and rehabilitative care, indicated that proposed statistical modeling identifies relevant codes mapped to 3 important domains: self-care, mobility, and cognition/communication.
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Estado Funcional , Pacientes Internos , Niño , Humanos , Estudios Retrospectivos , Actividades Cotidianas , AutocuidadoRESUMEN
INTRODUCTION: Limited evidence exists about which patient and stakeholder engagement practices support or hinder study teams as they negotiate different viewpoints in decisions about the design and conduct of patient-centered outcomes research. METHODS: We applied a multiple-embedded descriptive case study design for six studies funded by the Patient-Centered Outcomes Research Institute (PCORI). We interviewed 32 researchers and stakeholder partners, including patients, caregivers and clinicians, and reviewed documents related to each study (e.g., publications, and progress reports submitted to PCORI). FINDINGS: Overall, researchers reported that incorporating different viewpoints was a strength or opportunity to learn rather than something to be avoided or dreaded. Across cases, different viewpoints and priorities, often related to ethical or pragmatic considerations, emerged between researchers and stakeholders, between stakeholder groups (e.g., patients and clinicians) or within groups (e.g., amongst researchers). Examples of navigating different viewpoints arose across study phases. The length of time to resolve issues depended on how strongly people disagreed and the perceived importance or impact of decisions on the study. All cases used collaborative decision-making approaches, often described as consensus, throughout the study. Interviewees described consensus as using negotiation, compromise or working towards an agreeable decision. To encourage consensus, cases actively facilitated group discussions with an openness to diverse opinions, remained flexible and open to trying new things, referenced a ground rule or common goal and delegated decisions to partners or smaller workgroups. When viewpoints were not easily resolved, cases used different approaches to reach final decisions while maintaining relationships with partners, such as elevating decisions to leadership or agreeing to test out an approach. No one engagement structure (e.g., advisory group, coinvestigator) stood out as better able to manage different viewpoints. Teams adjusted engagement structures and behaviours to facilitate an overall culture of inclusion and respect. Partners acknowledged the intentional efforts of researchers to incorporate their perspectives, navigate challenges and communicate the value of partner input. CONCLUSION: By using collaborative decision-making in the early stages and throughout the study, researchers built trust with partners so that when decisions were difficult to resolve, partners still felt listened to and that their input mattered. PATIENT OR PUBLIC CONTRIBUTION: Members of the PCORI Patient Engagement Advisory Panel in 2019-2020 provided input into the design of the study, including the research questions and approaches to data collection and analysis.
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Evaluación del Resultado de la Atención al Paciente , Participación del Paciente , Humanos , Participación del Paciente/métodos , Proyectos de Investigación , Consenso , Academias e InstitutosRESUMEN
AIMS AND OBJECTIVES: Evidence suggests that preparing patients for surgery using nonpharmacological strategies reduces their anxiety. However, there is no consensus on what the best practices are. This study aims to answer the question: Are interventions using nonpharmacological therapies effective in reducing preoperative anxiety? BACKGROUND: Preoperative anxiety causes physiological and psychological adverse effects, with a negative effect on postoperative recovery. INTRODUCTION: According to the World Health Organization, between 266 and 360 million surgical procedures are performed annually worldwide, and it is estimated that more than 50% of patients will experience some degree of preoperative anxiety. DESIGN: Systematic review of systematic reviews with results of interventions aimed at mitigating preoperative anxiety. METHODS: A search was conducted for systematic reviews with meta-analyses published between 2012 and 2021 in Medline, Scopus, Web of Science and Cochrane Library. Quality was assessed using the AMSTAR-2 scale. The protocol was registered in PROSPERO. RESULTS: A total of 1016 studies were examined, of which 17 systematic reviews were selected, yielding 188 controlled trials with 16,884 participants. In adults, the most common intervention included music, followed by massage, in children virtual reality and clowns. Almost all controlled trials reported a reduction in preoperative anxiety after the intervention, of which almost half had statistically significant results. CONCLUSION: Interventions that include music, massage and virtual reality reduce preoperative anxiety and have shown that they are cost-effective, minimally invasive and with a low risk of adverse effects. Preoperative anxiety can be reduced through a short-term intervention involving nursing professionals as an alternative or complement to drugs. RELEVANCE TO CLINICAL PRACTICE: This review suggests that nursing professionals, in collaboration with other health professionals, should continue to conduct research on the reduction in preoperative anxiety. Further research in this area is needed, to reduce heterogeneity and consolidate the results. NO PATIENT OR PUBLIC CONTRIBUTION: Not applied to our study, as it is a systematic review of systematic reviews.