Quality and quantity of information in summary basis of decision documents issued by health Canada.
ABSTRACT: Health Canada's Summary Basis of Decision (SBD) documents outline the clinical trial information that was considered in approving a new drug. We examined the ability of SBDs to inform clinician decision-making. We asked if SBDs answered three questions that clinicians might have prior to prescribing a new drug: 1) Do the characteristics of patients enrolled in trials match those of patients in their practice? 2) What are the details concerning the drug's risks and benefits? 3) What are the basic characteristics of trials?14 items of clinical trial information were identified from all SBDs published on or before April 2012. Each item received a score of 2 (present), 1 (unclear) or 0 (absent). The unit of analysis was the individual SBD, and an overall SBD score was derived based on the sum of points for each item. Scores were expressed as a percentage of the maximum possible points, and then classified into five descriptive categories based on that score. Additionally, three overall 'component' scores were tallied for each SBD: "patient characteristics", "benefit/risk information" and "basic trial characteristics".161 documents, spanning 456 trials, were analyzed. The majority (126/161) were rated as having information sometimes present (score of >33 to 66%). No SBDs had either no information on any item, or 100% of the information. Items in the patient characteristics component scored poorest (mean component score of 40.4%), while items corresponding to basic trial information were most frequently provided (mean component score of 71%).The significant omissions in the level of clinical trial information in SBDs provide little to aid clinicians in their decision-making. Clinicians' preferred source of information is scientific knowledge, but in Canada, access to such information is limited. Consequently, we believe that clinicians are being denied crucial tools for decision-making.
Project description:Social and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order.Adults, aged ?18 years, were recruited using ResearchMatch.org for this randomized, parallel design study conducted in 2015 (data analyzed in 2015-2016). Three versions of the SBD measures, sharing the same items but in different orders of presentation (Versions 1-3), were developed. Randomized to six groups, participants completed each version at least 1 week apart (Weeks 1-3). Version order was counterbalanced across each administration and randomization was stratified by gender, race, and age. Main outcomes were effect of question order, completion time, and non-response rates.Of 781 participants, 624 (80%) completed the Week 1 questionnaire; median completion time for answering all SBD questions was 5 minutes, 583/624 participants answered all items, and no statistically significant differences associated with question order were observed when comparing responses across all versions. No significant differences in responses within assignment groups over time were found, with the exception of the stress measure for Group 5 (p=0.036).Question order did not significantly impact participant responses. Time to complete the questionnaire was brief, and non-response rate was low. Findings support the feasibility of using the Institute of Medicine-recommended questionnaire to capture SBDs.
Project description:PURPOSE:To compare importance ratings of patient-reported outcomes (PROs) items from the viewpoints of childhood cancer survivors, parents, and clinicians for further developing short-forms to use in survivorship care. METHODS:101 cancer survivors, 101 their parents, and 36 clinicians were recruited from St. Jude Children's Research Hospital. Participants were asked to select eight items that they deemed useful for clinical decision making from each of the four Patient-Reported Outcomes Measurement Information System Pediatric item banks. These item banks were pain interference (20 items), fatigue (23 items), psychological stress (19 items), and positive affect (37 items). RESULTS:Compared to survivors, clinicians rated more items across four domains that were statistically different than did parents (23 vs. 13 items). Clinicians rated five items in pain interference domain (ORs 2.33-6.01; p's?<?0.05) and three items in fatigue domain (ORs 2.22-3.80; p's?<?.05) as more important but rated three items in psychological stress domain (ORs 0.14-0.42; p's?<?.05) and six items in positive affect domain (ORs 0.17-0.35; p's?<?.05) as less important than did survivors. In contrast, parents rated seven items in positive affect domain (ORs 0.25-0.47; p's?<?.05) as less important than did survivors. CONCLUSIONS:Survivors, parents, and clinicians viewed importance of PRO items for survivorship care differently. These perspectives should be used to assist the development of PROs tools.
Project description:INTRODUCTION:Many patients who are discharged from the emergency department (ED) with a symptom-based discharge diagnosis (SBD) have post-discharge challenges related to lack of a definitive discharge diagnosis and follow-up plan. There is no well-defined method for identifying patients with a SBD without individual chart review. We describe a method for automated identification of SBDs from ICD-10 codes using the Unified Medical Language System (UMLS) Metathesaurus. METHODS:We mapped discharge diagnosis, with use of ICD-10 codes from a one-month period of ED discharges at an urban, academic ED to UMLS concepts and semantic types. Two physician reviewers independently manually identified all discharge diagnoses consistent with SBDs. We calculated inter-rater reliability for manual review and the sensitivity and specificity for our automated process for identifying SBDs against this "gold standard." RESULTS:We identified 3642 ED discharges with 1382 unique discharge diagnoses that corresponded to 875 unique ICD-10 codes and 10 UMLS semantic types. Over one third (37.5%, n = 1367) of ED discharges were assigned codes that mapped to the "Sign or Symptom" semantic type. Inter-rater reliability for manual review of SBDs was very good (0.87). Sensitivity and specificity of our automated process for identifying encounters with SBDs were 84.7% and 96.3%, respectively. CONCLUSION:Use of our automated process to identify ICD-10 codes that classify into the UMLS "Sign or Symptom" semantic type identified the majority of patients with a SBD. While this method needs refinement to increase sensitivity of capture, it has potential to automate an otherwise highly time-consuming process. This novel use of informatics methods can facilitate future research specific to patients with SBDs.
Project description:Earlier, we reported on the design of sulfated benzofuran dimers (SBDs) as allosteric inhibitors of thrombin (Sidhu et al. J. Med. Chem.201154 5522-5531). To identify the site of binding of SBDs, we studied thrombin inhibition in the presence of exosite 1 and 2 ligands. Whereas hirudin peptide and heparin octasaccharide did not affect the IC(50) of thrombin inhibition by a high affinity SBD, the presence of full-length heparin reduced inhibition potency by 4-fold. The presence of ?' fibrinogen peptide, which recognizes Arg93, Arg97, Arg173, Arg175, and other residues, resulted in a loss of affinity that correlated with the ideal Dixon-Webb competitive profile. Replacement of several arginines and lysines of exosite 2 with alanine did not affect thrombin inhibition potency, except for Arg173, which displayed a 22-fold reduction in IC(50). Docking studies suggested a hydrophobic patch around Arg173 as a plausible site of SBD binding to thrombin. The absence of the Arg173-like residue in factor Xa supported the observed selectivity of inhibition by SBDs. Cellular toxicity studies indicated that SBDs are essentially nontoxic to cells at concentrations as high as 250 mg/kg. Overall, the work presents the localization of the SBD binding site, which could lead to allosteric modulators of thrombin that are completely different from all clinically used anticoagulants.
Project description:This work evaluates the performance of longitudinal item response (IR) theory models in shortened assessments using an existing model for part II and III of the MDS-UPDRS score. Based on the item information content, the assessment was reduced by removal of items in multiple increments and the models' ability to recover the item characteristics of the remaining items at each level was evaluated. This evaluation was done for both simulated and real data. The metric of comparison in both cases was the item information function. For real data, the impact of shortening on the estimated disease progression and drug effect was also studied. In the simulated data setting, the item characteristics did not differ between the full and the shortened assessments down to the lowest level of information remaining; indicating a considerable independence between items. In contrast when reducing the assessment in a real data setting, a substantial change in item information was observed for some of the items. Disease progression and drug effect estimates also decreased in the reduced assessments. These changes indicate a shift in the measured construct of the shortened assessment and warrant caution when comparing results from a partial assessment with results from the full assessment.
Project description:BACKGROUND:Clinicians recognise that some critically ill children are difficult-to-sedate. It may be possible to identify this clinical phenotype for sedation response using statistical modelling techniques adopted from machine learning. This requires identification of a finite number of variables to include in the statistical model. OBJECTIVE:To establish face and content validity for 17 candidate variables identified in the international literature as characteristic of the difficult-to-sedate child phenotype. METHODS:Paediatric critical care clinicians rated the relevance of 17 variables characterising the difficult-to-sedate child using a four-point scale ranging from not (1) to highly relevant (4). Face and content validity of these variables were assessed by calculating a mean score for each item and computing an item-level content validity index. Items with a mean score >1 were rated as having adequate face validity. An item-level content validity index ?0.70 indicated good to excellent content validity. SETTING AND PARTICIPANTS:Web-based survey emailed to members of the Pediatric Acute Lung Injury and Sepsis Investigators Network or the Society of Critical Care Medicine Pediatric Sedation Study Group. RESULTS:Of 411 possible respondents, 121 useable surveys were returned for a response rate of 29%. All items had a mean score >1, indicating adequate face validity. Ten of 17 items scored an item-level content validity index ?0.70. The highest scoring items were requiring three or more sedation classes simultaneously, daily modal sedation score indicating agitation, sedation score indicating agitation for 2 consecutive hours, receiving sedatives at a dose >90th percentile of the usual starting dose, and receiving intermittent paralytic doses for sedation. CONCLUSIONS:Computation of an item-level content validity index validated variables to include in statistical modelling of the difficult-to-sedate phenotype. The results indicate consensus among paediatric critical care clinicians that the majority of candidate variables identified through literature review are characteristic of the difficult-to-sedate child.
Project description:BACKGROUND:Little research has examined whether shared decision making (SDM) occurs in consultations for acute respiratory infections (ARIs), including what, and how, antibiotic benefits and harms are discussed. We aimed to analyse the extent and nature of SDM in consultations between GPs and patients with ARIs, and explore communication with and without the use of patient decision aids. METHODS:This was an observational study in Australian general practices, nested within a cluster randomised trial of decision aids (for acute otitis media [AOM], sore throat, acute bronchitis) designed for general practitioners (GPs) to use with patients, compared with usual care (no decision aids). Audio-recordings of consultations of a convenience sample of consenting patients seeing a GP for an ARI were independently analysed by two raters using the OPTION-12 (observing patient involvement in decision making) scale (maximum score of 100) and 5 items (about communicating evidence) from the Assessing Communication about Evidence and Patient Preferences (ACEPP) tool (maximum score of 5). Patients also self-completed a questionnaire post-consultation that contained items from CollaboRATE-5 (perceptions of involvement in the decision-making process), a decisional conflict scale, and a decision self-efficacy scale. Descriptive statistics were calculated for each measure. RESULTS:Thirty-six consultations, involving 13 GPs, were recorded (20 for bronchitis, 10 sore throat, 6 AOM). The mean (SD) total OPTION-12 score was 29.4 (12.5; range 4-54), with item 12 (need to review decision) the highest (mean?=?3) and item 10 (eliciting patients' preferred level of decision-making involvement) the lowest (mean?=?0.1). The mean (SD) total ACEPP score was 2 (1.6), with the item about discussing benefits scoring highest. In consultations where a decision aid was used (15, 42%), compared to the 21 usual care consultations, mean observer-assessed SDM scores (OPTION-12, ACEPP scores) were higher and antibiotic harms mentioned in all (compared to only 1) consultations. Patients generally reported high decision involvement and self-efficacy, and low decisional conflict. CONCLUSIONS:The extent of observer-assessed SDM between GPs and patients with ARIs was generally low. Balanced discussion of antibiotic benefits and harms occurred more often when decision aids were used.
Project description:BACKGROUND:Healthy Hearts Northwest (H2N) is a study of external support strategies to build quality improvement (QI) capacity in primary care with a focus on cardiovascular risk factors: appropriate aspirin use, blood pressure control, and tobacco screening/cessation. METHODS:To guide practice facilitator support, experts in practice transformation identified seven domains of QI capacity and mapped items from a previously validated medical home assessment tool to them. A practice facilitator (PF) met with clinicians and staff in each practice to discuss each item on the Quality Improvement Capacity Assessment (QICA) resulting in a practice-level response to each item. We examined the association between the QICA total and sub-scale scores, practice characteristics, a measure of prior experience with managing practice change, and performance on clinical quality measures (CQMs) for the three cardiovascular risk factors. RESULTS:The QICA score was associated with prior experience managing change and moderately associated with two of the three CQMs: aspirin use (r =?0.16, p =?0.049) and blood pressure control (r =?0.18, p =?0.013). Rural practices and those with 2-5 clinicians had lower QICA scores.. CONCLUSIONS:The QICA is useful for assessing QI capacity within a practice and may serve as a guide for both facilitators and primary care practices in efforts to build this capacity and improve measures of clinical quality. TRIAL REGISTRATION:This trial is registered with www.clinicaltrials.gov Identifier# NCT02839382, retrospectively registered on July 21, 2016.
Project description:BACKGROUND:To develop items for an early warning score (RECAP: REmote COVID-19 Assessment in Primary Care) for patients with suspected COVID-19 who need escalation to next level of care. METHODS:The study was based in UK primary healthcare. The mixed-methods design included rapid review, Delphi panel, interviews, focus groups and software development. Participants were 112 primary care clinicians and 50 patients recovered from COVID-19, recruited through social media, patient groups and snowballing. Using rapid literature review, we identified signs and symptoms which are commoner in severe COVID-19. Building a preliminary set of items from these, we ran four rounds of an online Delphi panel with 72 clinicians, the last incorporating fictional vignettes, collating data on R software. We refined the items iteratively in response to quantitative and qualitative feedback. Items in the penultimate round were checked against narrative interviews with 50 COVID-19 patients. We required, for each item, at least 80% clinician agreement on relevance, wording and cut-off values, and that the item addressed issues and concerns raised by patients. In focus groups, 40 clinicians suggested further refinements and discussed workability of the instrument in relation to local resources and care pathways. This informed design of an electronic template for primary care systems. RESULTS:The prevalidation RECAP-V0 comprises a red flag alert box and 10 assessment items: pulse, shortness of breath or respiratory rate, trajectory of breathlessness, pulse oximeter reading (with brief exercise test if appropriate) or symptoms suggestive of hypoxia, temperature or fever symptoms, duration of symptoms, muscle aches, new confusion, shielded list and known risk factors for poor outcome. It is not yet known how sensitive or specific it is. CONCLUSIONS:Items on RECAP-V0 align strongly with published evidence, clinical judgement and patient experience. The validation phase of this study is ongoing. TRIAL REGISTRATION NUMBER:NCT04435041.
Project description:The Lactobacillus amylovorus alpha-amylase starch binding domain (SBD) is a functional domain responsible for binding to insoluble starch. Structurally, this domain is dissimilar from other reported SBDs because it is composed of five identical tandem modules of 91 amino acids each. To understand adsorption phenomena specific to this SBD, the importance of their modular arrangement in relationship to binding ability was investigated. Peptides corresponding to one, two, three, four, or five modules were expressed as His-tagged proteins. Protein binding assays showed an increased capacity of adsorption as a function of the number of modules, suggesting that each unit of the SBD may act in an additive or synergic way to optimize binding to raw starch.