Design, methods, and reporting of impact studies of cardiovascular clinical prediction rules are suboptimal: a systematic review.

OBJECTIVES: To evaluate design, methods, and reporting of impact studies of cardiovascular clinical prediction rules (CPRs). STUDY DESIGN AND SETTING: We conducted a systematic review. Impact studies of cardiovascular CPRs were identified by forward citation and electronic database searches. We categorized the design of impact studies as appropriate for randomized and nonrandomized experiments, excluding uncontrolled before-after study. For impact studies with appropriate study design, we assessed the quality of methods and reporting. We compared the quality of methods and reporting between impact and matched control studies. RESULTS: We found 110 impact studies of cardiovascular CPRs. Of these, 65 (59.1%) used inappropriate designs. Of 45 impact studies with appropriate design, 31 (68.9%) had substantial risk of bias. Mean number of reporting domains that impact studies with appropriate study design adhered to was 10.2 of 21 domains (95% confidence interval, 9.3 and 11.1). The quality of methods and reporting was not clearly different between impact and matched control studies. CONCLUSION: We found most impact studies either used inappropriate study design, had substantial risk of bias, or poorly complied with reporting guidelines. This appears to be a common feature of complex interventions. Users of CPRs should critically evaluate evidence showing the effectiveness of CPRs.

A New Device for Fine-Needle Aspiration Cytology Consisting of a Vibrating Linear Resonant Actuator.

OBJECTIVE: To evaluate the efficacy of a new device for fine-needle aspiration cytology (FNAC) consisting of a vibrating linear resonant actuator (LRA). STUDY DESIGN: Prospective clinical study. METHODS: The LRA frequency was optimized by visualization of the needle motion using a high-speed camera. The FNAC device consists of a vibrating motor fixed to the stopper of a 5-ml syringe and piston. Upon insertion of the syringe needle into a thyroid nodule (with the stopper attached to the syringe piston), sufficient negative pressure with 1-ml suction was maintained. Subsequently, samples were obtained using vibration generated by an LRA or an eccentric rotating mass (ERM). Surgically resected thyroid specimens from 10 patients were evaluated. The number of follicular groups required for adequate diagnosis and the number of larger follicular groups were counted. Next, 254 thyroid nodules from 187 patients were also evaluated by FNAC. The inadequacy rate was determined, and final cytology was classified according to thyroid Bethesda categories. RESULTS: The optimized LRA frequency was 155 Hz. Both the LRA and ERM devices resulted in sufficient amounts of diagnostic material and achieved low inadequacy rates. The number of large follicular groups obtained was significantly greater with the LRA device compared with the ERM device. CONCLUSIONS: The vibrating device using an LRA for thyroid FNAC resulted in sufficient amounts of thyroid follicular groups and achieved low inadequacy rates. In addition, the LRA device allowed for collection of larger follicular groups sufficient to diagnose appropriate thyroid Bethesda categories. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E1393-E1399, 2021.

Effectiveness of different treatments in obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity, defined as daytime hypoventilation, sleep disorder breathing and obesity; during the past few years the prevalence of extreme obesity has markedly increased worldwide consequently increasing the prevalence of OHS. Patients with OHS have a lower quality of life and a higher risk of unfavourable cardiometabolic consequences. Early diagnosis and effective treatment can lead to significant improvement in patient outcomes; therefore, such data has noticeably raised interest in the management and treatment of this sleep disorder. This paper will discuss the findings on the main current treatment modalities OHS will be discussed.

Improving rheumatoid arthritis comparative effectiveness research through causal inference principles: systematic review using a target trial emulation framework.

OBJECTIVES: Target trial emulation is an intuitive design framework that encourages investigators to formulate their comparative effectiveness research (CER) question as a hypothetical randomised controlled trial (RCT). Our aim was to systematically review CER studies in rheumatoid arthritis (RA) to provide examples of design limitations that could be avoided using target trial emulation, and how these limitations might introduce bias. METHODS: We searched for head-to-head CER studies of biologic disease modifying anti-rheumatic drugs (DMARDs) in RA. Study designs were reviewed for seven components of the target trial emulation framework: eligibility criteria, treatment strategies, assignment procedures, follow-up period, outcome, causal contrasts of interest (ie, intention-to-treat (ITT) or per-protocol effect) and analysis plan. Hypothetical trials corresponding to the reported methods were assessed to identify design limitations that would have been avoided with an explicit target trial protocol. Analysis of the primary effectiveness outcome was chosen where multiple analyses were performed. RESULTS: We found 31 CER studies, of which 29 (94%) had at least one design limitation belonging to seven components. The most common limitations related to: (1) eligibility criteria: 19/31 (61%) studies used post-baseline information to define baseline eligibility; (2) causal contrasts: 25 (81%) did not define whether ITT or per-protocol effects were estimated and (3) assignment procedures: 13 (42%) studies did not account for confounding by indication or relied solely on statistical confounder selection. CONCLUSIONS: Design limitations were found in 94% of observational CER studies in RA. Target trial emulation is a structured approach for designing observational CER studies that helps to avoid potential sources of bias.

Bayesian adaptive designs for multi-arm trials: an orthopaedic case study.

BACKGROUND: Bayesian adaptive designs can be more efficient than traditional methods for multi-arm randomised controlled trials. The aim of this work was to demonstrate how Bayesian adaptive designs can be constructed for multi-arm phase III clinical trials and assess potential benefits that these designs offer. METHODS: We constructed several alternative Bayesian adaptive designs for the Collaborative Ankle Support Trial (CAST), which was a randomised controlled trial that compared four treatments for severe ankle sprain. These designs incorporated response adaptive randomisation (RAR), arm dropping, and early stopping for efficacy or futility. We studied the operating characteristics of the Bayesian designs via simulation. We then virtually re-executed the trial by implementing the Bayesian adaptive designs using patient data sampled from the CAST study to demonstrate the practical applicability of the designs. RESULTS: We constructed five Bayesian adaptive designs, each of which had high power and recruited fewer patients on average than the original designs target sample size. The virtual executions showed that most of the Bayesian designs would have led to trials that declared superiority of one of the interventions over the control. Bayesian adaptive designs with RAR or arm dropping were more likely to allocate patients to better performing arms at each interim analysis. Similar estimates and conclusions were obtained from the Bayesian adaptive designs as from the original trial. CONCLUSIONS: Using CAST as an example, this case study shows how Bayesian adaptive designs can be constructed for phase III multi-arm trials using clinically relevant decision criteria. These designs demonstrated that they can potentially generate earlier results and allocate more patients to better performing arms. We recommend the wider use of Bayesian adaptive approaches in phase III clinical trials. TRIAL REGISTRATION: CAST study registration ISRCTN, ISRCTN37807450. Retrospectively registered on 25 April 2003.

Closed testing of each group versus the others combined in a multiple group analysis.

BACKGROUND: Many studies, such as a study of comparative effectiveness, entail a comparison of the beneficial and adverse effects of multiple K> 2 competing therapies. Often, the analysis consists of a comparison of the K groups using an omnibus (T2-like) test for any difference among the groups followed by pairwise comparisons with adjustments for multiple tests. METHODS: We evaluate the properties of an analysis strategy in which each group is compared to the average of the others in hopes of establishing the overall superiority (or harm) of at least one of the therapies. Testing of one-versus-others can be accomplished for virtually any model using simple tests, and the type I error probability α can be controlled by conducting such tests under the closed testing principle. Testing using linear models, the family of generalized linear models, and Cox proportional hazards models is described with examples. RESULTS: Since each tested hypothesis compares one treatment to the average of the others, the K-level null hypothesis in the tree of closed testing is equivalent to any of the (K-1)-level tests, thus reducing the number of tests required. This applies to linear, generalized linear, and Cox proportional hazards models. While the Bonferroni, Holm, and Hommel procedures preserve the desired level α, all are conservative relative to closed one-versus-others testing and closed testing in general provides greater power. CONCLUSION: Testing each of the multiple treatments versus the average of the others is readily and efficiently conducted under the closed testing principle and may be especially useful in the assessment of studies of comparative effectiveness.

Choosing important health outcomes for comparative effectiveness research: 5th annual update to a systematic review of core outcome sets for research.

BACKGROUND: A systematic review of core outcome sets (COS) for research is updated annually to populate an online database. It is a resource intensive review to do annually but automation techniques have potential to aid the process. The production of guidance and standards in COS development means that there is now an expectation that COS are being developed and reported to a higher standard. This is the fifth update to the systematic review and will explore these issues. METHODS: Searches were carried out to identify studies published or indexed in 2018. Automated screening methods were used to rank the citations in order of relevance. The cut-off for screening was set to the top 25% in ranked priority order, following development and validation of the algorithm. Studies were eligible for inclusion if they reported the development of a COS, regardless of any restrictions by age, health condition or setting. COS were assessed against each of the Core Outcome Set-STAndards for Development (COS-STAD). RESULTS: Thirty studies describing the development of 44 COS were included in this update. Six COS (20%) were deemed to have met all 12 criteria representing the 11 minimum standards for COS development (range = 4 to 12 criteria, median = 10 criteria). All 30 COS studies met all four minimum standards for scope. Twenty-one (70%) COS met all three minimum standards for stakeholders. Twenty-three studies (77%) included patients with the condition or their representatives. The number of countries involved in the development of COS ranged from 1 to 39 (median = 10). Six studies (20%) met all four minimum standards [five criteria] for the consensus process. CONCLUSION: Automated ranking was successfully used to assist the screening process and reduce the workload of this systematic review update. With the provision of guidelines, COS are better reported and being developed to a higher standard.

Comparative Clinical Effectiveness Research Focused on Community-Based Delivery of Palliative Care: Overview of the Patient-Centered Outcomes Research Institute's Funding Initiative.

Palliative care is a growing specialty that addresses the needs of individuals diagnosed with advanced illness and their caregivers. Although palliative care has been shown to improve a variety of patient- and caregiver-centered outcomes, access to comprehensive palliative care services for patients is often limited. There is a need to identify the most effective approaches to delivering palliative care to patients in community settings. In fiscal year 2017, based on extensive input from a diverse set of stakeholders, the Patient-Centered Outcomes Research Institute (PCORI) funded nine multisite comparative clinical effectiveness research (CER) trials focused on community-based delivery of palliative care for a total investment of $80 million. These studies, focusing on advance care planning and models of palliative care delivery, represent some of the largest most complex palliative care trials funded to date. Each study evaluates both patient and caregiver outcomes, and together, these trials include a broad range of health conditions, interventions, and settings of care. PCORI has also fostered a learning network of the funded awardees to facilitate the successful conduct of these CER studies and to support awardee efforts to develop collaborative products relevant to advancing the field of palliative care research and practice. The protocols of each of the nine trials, detailed in this issue, demonstrate the expansive reach of the investment PCORI has made in an effort to further the research agenda and provide substantive research evidence in stakeholder-identified areas of need in the field of palliative care.

A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

BACKGROUND: Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. OBJECTIVE: To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. METHODS: Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. RESULTS: Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. CONCLUSIONS: This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. DISCLOSURES: Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.

Perceived Effectiveness of Anti-Marijuana Messages in Adult Users and Nonusers: An Examination of Responses to Messages About Marijuana's Effects on Cognitive Performance, Driving, and Health.

OBJECTIVE: Marijuana use is associated with negative cognitive and health outcomes and risky driving. Given the rapidly changing policies regarding legal recreational and medicinal marijuana use, it is important to examine what types of marijuana prevention messages may be effective in minimizing such outcomes. This study examined cognitive and affective responses to anti-marijuana public health messages in a sample of adult marijuana users and nonusers to determine the correlates of perceived message effectiveness. METHOD: Participants (N = 203; mean age = 37.7 years) were adult marijuana users and nonusers recruited via Amazon Mechanical Turk (August 2017). After completing self-report measures of marijuana use, they viewed six anti-marijuana messages presented in a random order, addressing marijuana's effects in each of three topic areas: cognitive performance, driving, and adverse health outcomes (e.g., two messages per topic). Participants completed assessments of cognitive and affective perceptions after viewing each message. For each message topic, a linear regression model was used to determine which cognitive and affective perceptions were most predictive of perceived message effectiveness. RESULTS: For all message topics, nonusers perceived the messages as more effective than did users (p < .001). In the majority of analyses, greater message effectiveness was associated with increased perceived harm of marijuana and increased liking of the message. For driving and health messages, greater message effectiveness was also significantly correlated with lower pleasant affect. CONCLUSIONS: The findings suggest that audience perceptions may be uniquely predictive of message effectiveness, depending on the topic.

Facilitators and barriers to successful recruitment into a large comparative effectiveness trial: a qualitative study.

Background: Recruitment of participants into research studies, especially individuals from minority groups, is challenging; lack of diversity may lead to biased findings. Aim: To explore beliefs about research participation among individuals who were approached and eligible for the GRADE study. Methods: In-depth qualitative telephone interviews with randomized participants (n = 25) and eligible individuals who declined to enroll (n = 26). Results: Refusers and consenters differed in trust and perceptions of risk, benefits and burden of participation. Few participants understood how comparative effectiveness research differed from other types of trials; however, some features of comparative effectiveness research were perceived as lower risk. Conclusion: We identified facilitators and addressable barriers to participation in research studies.

US young adults' perceived effectiveness of draft pictorial e-cigarette warning labels.

SIGNIFICANCE: Research shows that pictorial warning labels for cigarettes are more effective than text-only warnings, and preliminary work suggests that pictorial warnings could also be considered for electronic cigarettes (e-cigarettes). Pictorial warnings may be important for maximising their effectiveness among young people and enhancing the salience of the single nicotine addiction warning required for e-cigarettes to date in the USA. This study collected pilot data about the perceived effectiveness of draft e-cigarette pictorial warnings. METHODS: Participants were 876 young adults (ages 18-29) recruited through Amazon Mechanical Turk who completed an online e-cigarette survey in 2018. Participants viewed and ranked five versions of the same e-cigarette nicotine addiction warning message-four pictorial and one text-only-on their perceived noticeability, likelihood of capturing young people's attention, memorability, relevance to the addiction warning text and overall effectiveness in warning people about e-cigarette risks. For each outcome, presentation of the five warning versions was randomised. Pictorials included symbolic images of risk and addiction, and of priority audiences for the warning (ie, young people). RESULTS: For all outcomes, pictorial warnings were ranked higher than the text-only warning, and the warning using a yellow triangle caution icon was ranked highest for all outcomes. The text-only warning was ranked as the least likely to be effective for all four outcomes in which it was assessed. Trends were similar for current e-cigarette users and non-users. CONCLUSIONS: Future research should assess perceptions and the appropriateness of pictorial imagery for e-cigarette warnings and test their efficacy against text-only warnings experimentally.

Alternative Conversion Methods for Transition Probabilities in State-Transition Models: Validity and Impact on Comparative Effectiveness and Cost-Effectiveness.

Background. In state-transition models (STMs), decision problems are conceptualized using health states and transitions among those health states after predefined time cycles. The naive, commonly applied method (C) for cycle length conversion transforms all transition probabilities separately. In STMs with more than 2 health states, this method is not accurate. Therefore, we aim to describe and compare the performance of method C with that of alternative matrix transformation methods. Design. We compare 2 alternative matrix transformation methods (Eigenvalue method [E], Schure-Padé method [SP]) to method C applied in an STM of 3 different treatment strategies for women with breast cancer. We convert the given annual transition matrix into a monthly-cycle matrix and evaluate induced transformation errors for the transition matrices and the long-term outcomes: life years, quality-adjusted life-years, costs and incremental cost-effectiveness ratios, and the performance related to the decisions. In addition, we applied these transformation methods to randomly generated annual transition matrices with 4, 7, 10, and 20 health states. Results. In theory, there is no generally applicable correct transformation method. Based on our simulations, SP resulted in the smallest transformation-induced discrepancies for generated annual transition matrices for 2 treatment strategies. E showed slightly smaller discrepancies than SP in the strategy, where one of the direct transitions between health states was excluded. For long-term outcomes, the largest discrepancy occurred for estimated costs applying method C. For higher dimensional models, E performs best. Conclusions. In our modeling examples, matrix transformations (E, SP) perform better than transforming all transition probabilities separately (C). Transition probabilities based on alternative conversion methods should therefore be applied in sensitivity analyses.

Preference option randomized design (PORD) for comparative effectiveness research: Statistical power for testing comparative effect, preference effect, selection effect, intent-to-treat effect, and overall effect.

Comparative effectiveness research trials in real-world settings may require participants to choose between preferred intervention options. A randomized clinical trial with parallel experimental and control arms is straightforward and regarded as a gold standard design, but by design it forces and anticipates the participants to comply with a randomly assigned intervention regardless of their preference. Therefore, the randomized clinical trial may impose impractical limitations when planning comparative effectiveness research trials. To accommodate participants' preference if they are expressed, and to maintain randomization, we propose an alternative design that allows participants' preference after randomization, which we call a "preference option randomized design (PORD)". In contrast to other preference designs, which ask whether or not participants consent to the assigned intervention after randomization, the crucial feature of preference option randomized design is its unique informed consent process before randomization. Specifically, the preference option randomized design consent process informs participants that they can opt out and switch to the other intervention only if after randomization they actively express the desire to do so. Participants who do not independently express explicit alternate preference or assent to the randomly assigned intervention are considered to not have an alternate preference. In sum, preference option randomized design intends to maximize retention, minimize possibility of forced assignment for any participants, and to maintain randomization by allowing participants with no or equal preference to represent random assignments. This design scheme enables to define five effects that are interconnected with each other through common design parameters-comparative, preference, selection, intent-to-treat, and overall/as-treated-to collectively guide decision making between interventions. Statistical power functions for testing all these effects are derived, and simulations verified the validity of the power functions under normal and binomial distributions.

Psychometrics: Trust, but Verify.

There is a continued mandate for practicing evidence-based medicine and the prerequisite rigorous analysis of the comparative effectiveness of alternative treatments. There is also an increasing emphasis on delivering value-based health care. Both these high priorities and their related endeavors require correct information about the outcomes of care. Accurately measuring and confirming health care outcomes are thus likely now of even greater importance. The present basic statistical tutorial focuses on the germane topic of psychometrics. In its narrower sense, psychometrics is the science of evaluating the attributes of such psychological tests. However, in its broader sense, psychometrics is concerned with the objective measurement of the skills, knowledge, and abilities, as well as the subjective measurement of the interests, values, and attitudes of individuals-both patients and their clinicians. While psychometrics is principally the domain and content expertise of psychiatry, psychology, and social work, it is also very pertinent to patient care, education, and research in anesthesiology, perioperative medicine, critical care, and pain medicine. A key step in selecting an existing or creating a new health-related assessment tool, scale, or survey is confirming or establishing the usefulness of the existing or new measure; this process conventionally involves assessing its reliability and its validity. Assessing reliability involves demonstrating that the measurement instrument generates consistent and hence reproducible results-in other words, whether the instrument produces the same results each time it is used in the same setting, with the same type of subjects. This includes interrater reliability, intrarater reliability, test-retest reliability, and internal reliability. Assessing validity is answering whether the instrument is actually measuring what it is intended to measure. This includes content validity, criterion validity, and construct validity. In evaluating a reported set of research data and its analyses, in a similar manner, it is important to assess the overall internal validity of the attendant study design and the external validity (generalizability) of its findings.

Psychotherapy for eating disorders: A meta-analysis of direct comparisons.

Objective: We conducted a meta-analysis of randomized controlled trials (RCTs) of bona fide psychotherapy for adults with eating disorders (EDs). Method: Thirty-five RCTs with 54 direct comparisons were included. The majority of RCTs included participants with bulimia nervosa and/or binge-ED, while only two RCTs included participants with anorexia nervosa, and three RCTs included participants with an ED not otherwise specified. Results: There was a clear advantage of bona fide psychotherapy over wait-list controls. Bona fide psychotherapy was superior to non-bona fide treatment; however, the majority of results were not stable. There were no significant differences between bona fide cognitive-behavioral therapy (CBT) and bona fide non-CBT, with the exception of bona fide CBT resulting in greater reductions in ED psychopathology assessed by the ED Examination, which primarily assesses maintenance factors according to the CBT model. Conclusions: Generally, the results indicate that any bona fide psychotherapy will be equally effective. While the number of trials remains modest, we hope that as more research becomes available, treatment guidelines can be updated, and more evidence-based treatment options will be available for treating EDs.

Are Publicly Funded Health Databases Geographically Detailed and Timely Enough to Support Patient-Centered Outcomes Research?

Emerging health care research paradigms such as comparative effectiveness research (CER), patient-centered outcome research (PCOR), and precision medicine (PM) share one ultimate goal: constructing evidence to provide the right treatment to the right patient at the right time. We argue that to succeed at this goal, it is crucial to have both timely access to individual-level data and fine geographic granularity in the data. Existing data will continue to be an important resource for observational studies as new data sources are developed. We examined widely used publicly funded health databases and population-based survey systems and found four ways they could be improved to better support the new research paradigms: (1) finer and more consistent geographic granularity, (2) more complete geographic coverage of the US population, (3) shorter time from data collection to data release, and (4) improved environments for restricted data access. We believe that existing data sources, if utilized optimally, and newly developed data infrastructures will both play a key role in expanding our insight into what treatments, at what time, work for each patient.

Two-stage residual inclusion for survival data and competing risks-An instrumental variable approach with application to SEER-Medicare linked data.

Instrumental variable is an essential tool for addressing unmeasured confounding in observational studies. Two-stage predictor substitution (2SPS) estimator and two-stage residual inclusion (2SRI) are two commonly used approaches in applying instrumental variables. Recently, 2SPS was studied under the additive hazards model in the presence of competing risks of time-to-events data, where linearity was assumed for the relationship between the treatment and the instrument variable. This assumption may not be the most appropriate when we have binary treatments. In this paper, we consider the 2SRI estimator under the additive hazards model for general survival data and in the presence of competing risks, which allows generalized linear models for the relation between the treatment and the instrumental variable. We derive the asymptotic properties including a closed-form asymptotic variance estimate for the 2SRI estimator. We carry out numerical studies in finite samples and apply our methodology to the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database comparing radical prostatectomy versus conservative treatment in early-stage prostate cancer patients.

Comparing drug effectiveness in children: A systematic review.

PURPOSE: The purpose of the study is to assess the current state of the art in pediatric comparative effectiveness research, potential gaps, and areas for improvement. METHODS: Relevant articles from inception to February 2015 were retrieved from Embase and Medline. We sequentially screened titles, abstracts, and full texts, with independent validation. Data regarding general information and study methods including statistical analysis were extracted. Study quality was assessed using Newcastle-Ottawa Scale (NOS). Investigated drugs were ranked and compared with data on the prevalence of pediatric drug use. RESULTS: Three thousand nine hundred twenty-six abstracts were screened for eligibility and inclusion, and 164 articles were included in the review. Most studies were from North America (46.7%). Only 78 studies (47.6%) reported the design: 90.8% were cohort studies. Neonates were least frequently investigated. The drugs that were most often studied included systemic antibacterials (11.4%), psycholeptics (7.9%), and antiepileptics (7.6%). Adjustment for confounding was made using propensity scores in 8.5% of the studies. Studies that did not report the design were of lower quality. Many effectiveness studies were done on antineoplastic agents, which are not frequently used and few studies on analgesics and drugs for obstructive airway diseases which are frequently prescribed. CONCLUSIONS: There is ample opportunity to improve comparative effectiveness research for drugs used in pediatrics. Routinely prescribed drugs were seldom investigated. Modern methods for confounding adjustment, such as propensity scores, were rarely used.

Statistical analysis plan for a cluster-randomized crossover trial comparing the effectiveness and safety of a flexible family visitation model for delirium prevention in adult intensive care units (the ICU Visits Study).

BACKGROUND: Most adult intensive care units (ICUs) worldwide adopt restrictive family visitation models (RFVMs). However, evidence, mostly from non-randomized studies, suggests that flexible adult ICU visiting hours are safe policies that can result in benefits such as prevention of delirium and increase in satisfaction with care. Accordingly, the ICU Visits Study was designed to compare the effectiveness and safety of a flexible family visitation model (FFVM) vs. an RFVM on delirium prevention among ICU patients, and also to analyze its potential effects on family members and ICU professionals. METHODS/DESIGN: The ICU Visits Study is a cluster-randomized crossover trial which compares an FFVM (12 consecutive ICU visiting hours per day) with an RFVM (< 4.5 ICU visiting hours per day) in 40 Brazilian adult ICUs. Participant ICUs are randomly assigned to either an FFVM or RFVM in a 1:1 ratio. After enrollment and follow-up of 25 patients, each ICU is crossed over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome is the cumulative incidence of delirium measured by the Confusion Assessment Method for the ICU. Secondary and tertiary outcomes include relevant measures of effectiveness and safety of ICU visiting policies among patients, family members, and ICU professionals. Herein, we describe all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of this study. This pre-specified statistical analysis plan was written and submitted without knowledge of the study data. DISCUSSION: This a priori statistical analysis plan aims to enhance the transparency of our study, facilitating unbiased analyses of ICU visit study data, and provide guidance for statistical analysis for groups conducting studies in the same field. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02932358 . Registered on 11 October 2016.