Matches in SemOpenAlex for { <https://semopenalex.org/work/W4296513710> ?p ?o ?g. }
- W4296513710 endingPage "e689" @default.
- W4296513710 startingPage "e674" @default.
- W4296513710 abstract "Randomised controlled trials (RCTs) inform prescription guidelines, but stringent eligibility criteria exclude individuals with vulnerable characteristics, which we define as comorbidities, concomitant medication use, and vulnerabilities due to age. Poor external validity can result in inadequate treatment decision information. Our first aim was to quantify the extent of exclusion of individuals with vulnerable characteristics from RCTs for all prescription drugs. Our second aim was to quantify the prevalence of individuals with vulnerable characteristics from population electronic health records who are actively prescribed such drugs. In tandem, these two aims will allow us to assess the representativeness between RCT and real-world populations and identify vulnerable populations potentially at risk of inadequate treatment decision information. When a vulnerable population is highly excluded from RCTs but has a high prevalence of individuals actively being prescribed the same medication, there is likely to be a gap in treatment decision information. Our third aim was to investigate the use of real-world evidence in contributing towards quantifying missing treatment risk or benefit through an observational study.We extracted RCTs from ClinicalTrials.gov from its inception to April 28, 2021, and primary care records from the Clinical Practice Research Datalink Gold database from Jan 1, 1998, to Dec 31, 2020. We referred to the British National Formulary to classify prescription drugs into drug categories. We conducted descriptive analyses and quantified RCT exclusion and prevalence of individuals with vulnerable characteristics for comparison to identify populations without treatment decision information. Exclusion and prevalence were assessed separately for different age groups, individual clinical specialities, and for quantities of concomitant conditions by clinical specialities, where multimorbidity was defined as having two or more clinical specialties, and medications prescribed, where polypharmacy was defined as having five or more medications prescribed. Population trends of individuals with multimorbidity or polypharmacy were assessed separately by age group. We conducted an observational cohort study to validate the use of real-world evidence in contributing towards quantifying treatment risk or benefit for patients with dementia on anti-dementia drugs with and without a contraindicated clinical speciality. To do so, we identified the clinical specialities that anti-dementia drug RCTs highly excluded yet had corresponding high prevalence in the real-world population, forming the groups with highest risk of having scarce treatment decision information. Cox regression was used to assess if the risk of mortality outcomes differs between both groups.43 895 RCTs from ClinicalTrials.gov and 5 685 738 million individuals from primary care records were used. We considered 989 unique drugs and 286 conditions across 13 drug-category cohorts. For the descriptive analyses, the median RCT exclusion proportion across 13 drug categories was 81·5% (IQR 76·7-85·5) for adolescents (aged <18 years), 26·3% (IQR 21·0-29·5) for individuals older than 60 years, 40·5% (IQR 33·7-43·0) for individuals older than 70 years, and 52·9% (IQR 47·1-56·0) for individuals older than 80 years. Multimorbidity had a median exclusion proportion of 91·1% (IQR 88·9-91·8) and median prevalence of 41·0% (IQR 34·9-46·0). Concomitant medication use had a median exclusion proportion of 52·5% (IQR 50·0-53·7) and a median prevalence of 94·3% (IQR 84·3-97·2), and polypharmacy had a median prevalence of 47·7% (IQR 38·0-56·1). Population trends show increasing multimorbidity with age and consistently high polypharmacy across age groups. Populations with cardiovascular or otorhinolaryngological comorbidities had the highest risk of having scarce treatment decision information. For the observational study, populations with cardiovascular or psychiatric comorbidities had highest risk of having scarce treatment decision information. Patients with dementia with an anti-dementia prescription and contraindicated cardiovascular condition had a higher risk of mortality (hazard ratio [HR] 1·20 [95% CI 1·13-1·28 ; p<0·0001]) compared with patients with dementia without a contraindicated cardiovascular condition. Patients with dementia with comorbid delirium (HR 1·25 [95% CI 1·06-1·48]; p<0·0088), intellectual disability (HR 2·72 [95% CI 1·53-4·81]; p=0·0006), and schizophrenia and schizotypal delusional disorders (HR 1·36 [95% CI 1·02-1·82]; p=0·036) had a higher risk of mortality compared with patients with dementia without these conditions.Overly stringent RCT exclusion criteria do not appropriately account for the heterogeneity of vulnerable characteristics observed in real-world populations. Treatment decision information is scarce for such individuals, which might affect health outcomes. We discuss the challenges facing the inclusivity of such individuals and highlight the strength of real-world evidence as an integrative solution in complementing RCTs and increasing the completeness of evidence-based medicine assessments in evaluating the effectiveness of treatment decisions.Wellcome Trust, National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Academy of Medical Sciences, and the University College London Overseas Research Scholarship." @default.
- W4296513710 created "2022-09-21" @default.
- W4296513710 creator A5015984989 @default.
- W4296513710 creator A5025964083 @default.
- W4296513710 creator A5050747301 @default.
- W4296513710 creator A5055076799 @default.
- W4296513710 creator A5057543019 @default.
- W4296513710 creator A5073010916 @default.
- W4296513710 date "2022-10-01" @default.
- W4296513710 modified "2023-10-17" @default.
- W4296513710 title "Comparing clinical trial population representativeness to real-world populations: an external validity analysis encompassing 43 895 trials and 5 685 738 individuals across 989 unique drugs and 286 conditions in England" @default.
- W4296513710 cites W1964172790 @default.
- W4296513710 cites W1982021576 @default.
- W4296513710 cites W1983117789 @default.
- W4296513710 cites W2017978677 @default.
- W4296513710 cites W2025315774 @default.
- W4296513710 cites W2043990618 @default.
- W4296513710 cites W2048353385 @default.
- W4296513710 cites W2106952837 @default.
- W4296513710 cites W2113976466 @default.
- W4296513710 cites W2144867139 @default.
- W4296513710 cites W2153244834 @default.
- W4296513710 cites W2168272173 @default.
- W4296513710 cites W2171466942 @default.
- W4296513710 cites W2288876626 @default.
- W4296513710 cites W2467710456 @default.
- W4296513710 cites W2525999137 @default.
- W4296513710 cites W2791881027 @default.
- W4296513710 cites W2805062403 @default.
- W4296513710 cites W2885447570 @default.
- W4296513710 cites W2900081888 @default.
- W4296513710 cites W2900671079 @default.
- W4296513710 cites W2905544274 @default.
- W4296513710 cites W2943458032 @default.
- W4296513710 cites W2944890781 @default.
- W4296513710 cites W2963955749 @default.
- W4296513710 cites W2973419479 @default.
- W4296513710 cites W2993268422 @default.
- W4296513710 cites W3008105828 @default.
- W4296513710 cites W3009768886 @default.
- W4296513710 cites W3021472140 @default.
- W4296513710 cites W3023095763 @default.
- W4296513710 cites W3046454849 @default.
- W4296513710 cites W3098511379 @default.
- W4296513710 cites W3129769620 @default.
- W4296513710 cites W3140760072 @default.
- W4296513710 cites W3157316811 @default.
- W4296513710 cites W3201751808 @default.
- W4296513710 cites W3211658667 @default.
- W4296513710 cites W4200162826 @default.
- W4296513710 cites W4213181205 @default.
- W4296513710 cites W4220966962 @default.
- W4296513710 doi "https://doi.org/10.1016/s2666-7568(22)00186-6" @default.
- W4296513710 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36150402" @default.
- W4296513710 hasPublicationYear "2022" @default.
- W4296513710 type Work @default.
- W4296513710 citedByCount "19" @default.
- W4296513710 countsByYear W42965137102022 @default.
- W4296513710 countsByYear W42965137102023 @default.
- W4296513710 crossrefType "journal-article" @default.
- W4296513710 hasAuthorship W4296513710A5015984989 @default.
- W4296513710 hasAuthorship W4296513710A5025964083 @default.
- W4296513710 hasAuthorship W4296513710A5050747301 @default.
- W4296513710 hasAuthorship W4296513710A5055076799 @default.
- W4296513710 hasAuthorship W4296513710A5057543019 @default.
- W4296513710 hasAuthorship W4296513710A5073010916 @default.
- W4296513710 hasBestOaLocation W42965137101 @default.
- W4296513710 hasConcept C100406419 @default.
- W4296513710 hasConcept C105795698 @default.
- W4296513710 hasConcept C126322002 @default.
- W4296513710 hasConcept C15744967 @default.
- W4296513710 hasConcept C168563851 @default.
- W4296513710 hasConcept C174106493 @default.
- W4296513710 hasConcept C23131810 @default.
- W4296513710 hasConcept C2426938 @default.
- W4296513710 hasConcept C2908647359 @default.
- W4296513710 hasConcept C33923547 @default.
- W4296513710 hasConcept C37381756 @default.
- W4296513710 hasConcept C39896193 @default.
- W4296513710 hasConcept C40993552 @default.
- W4296513710 hasConcept C512399662 @default.
- W4296513710 hasConcept C535046627 @default.
- W4296513710 hasConcept C71924100 @default.
- W4296513710 hasConcept C77805123 @default.
- W4296513710 hasConcept C98274493 @default.
- W4296513710 hasConcept C99454951 @default.
- W4296513710 hasConceptScore W4296513710C100406419 @default.
- W4296513710 hasConceptScore W4296513710C105795698 @default.
- W4296513710 hasConceptScore W4296513710C126322002 @default.
- W4296513710 hasConceptScore W4296513710C15744967 @default.
- W4296513710 hasConceptScore W4296513710C168563851 @default.
- W4296513710 hasConceptScore W4296513710C174106493 @default.
- W4296513710 hasConceptScore W4296513710C23131810 @default.
- W4296513710 hasConceptScore W4296513710C2426938 @default.
- W4296513710 hasConceptScore W4296513710C2908647359 @default.
- W4296513710 hasConceptScore W4296513710C33923547 @default.
- W4296513710 hasConceptScore W4296513710C37381756 @default.
- W4296513710 hasConceptScore W4296513710C39896193 @default.