scholarly journals Three-step matching algorithm to enhance between-group comparability and minimize confounding in comparative effectiveness studies

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Chen-Yi Yang ◽  
Shihchen Kuo ◽  
Edward Chia-Cheng Lai ◽  
Huang-Tz Ou
Keyword(s):  
Propensity Scores ◽  
Medication Possession Ratio ◽  
Reliability And Validity ◽  
Study Drug ◽  
Patient Characteristics ◽  
Study Groups ◽  
Research Database ◽  
Matching Algorithm ◽  
Glucagon Like Peptide 1 ◽  
Confounder Adjustment

AbstractWe developed a three-step matching algorithm to enhance the between-group comparability for comparative drug effect studies involving prevalent new-users of the newer study drug versus older comparator drug(s). The three-step matching scheme is to match on: (1) index date of initiating the newer study drug to align the cohort entry time between study groups, (2) medication possession ratio measures that consider prior exposure to all older comparator drugs, and (3) propensity scores estimated from potential confounders. Our approach is illustrated with a comparative cardiovascular safety study of glucagon-like peptide-1 receptor agonist (GLP-1ra) versus sulfonylurea (SU) in type 2 diabetes patients using Taiwan’s National Health Insurance Research Database 2003–2015. 66% of 3195 GLP-1ra users had previously exposed to SU. The between-group comparability was well-achieved after implementing the matching algorithm (i.e., standardized mean difference < 0.2 for all baseline patient characteristics). Compared to SU, the use of GLP-1ra yielded a significantly reduced risk of the primary composite cardiovascular events (hazard ratio [95% confidence interval]: 0.71 [0.54–0.95], p = 0.022). Our matching scheme can enhance the between-group comparability in prevalent new-user cohort designs to minimize time-related bias, improve confounder adjustment, and ensure the reliability and validity of study findings.

Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA508-CRA508 ◽  
Author(s):  
R. E. Aubert ◽  
E. J. Stanek ◽  
J. Yao ◽  
J. R. Teagarden ◽  
M. Subar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Active Form ◽  
Plasma Concentrations ◽  
Medication Possession Ratio ◽  
Study Groups ◽  
Rank Test ◽  
Research Database ◽  
Concurrent Use ◽  
Cyp2d6 Inhibitors

CRA508 Background: Tamoxifen (TAM) is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Diminished CYP2D6 function, both by genetic variation or concurrent use of pharmacologic inhibitors, can significantly reduce endoxifen plasma concentrations and may lead to reduced TAM effectiveness. Methods: We interrogated an integrated research database comprised of de-identified medical and pharmacy claims (Rx) data for 10.7 million U.S. health plan members to identify women with breast cancer (BrCa) new to TAM therapy in a 30-month period from 2003 to 2005, and investigated the risk of recurrent BrCa as a function of concurrent use of potent and moderate inhibitors of CYP2D6. Inclusion criteria were: greater than or equal to 24 months of follow-up data and adherence to TAM (medication possession ratio > 70%) over 2 years (N = 1,298). Disease recurrence was defined by BrCa ICD-9 codes or CPT codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy occurring at least 6 months after the index TAM Rx. Two study groups were identified: TAM alone (N = 945) or TAM + a CYP2D6 inhibitor concomitantly (N = 353). BrCa recurrence rates were compared using Kaplan-Meier analysis with log-rank test, and univariate hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards model. Results: The study groups were similar at baseline. Median age was 52 years (TAM) and 53 years (TAM + CYP2D6 inhibitor). Interventions performed in the TAM alone group included mastectomy in 54%, lumpectomy in 36%, and radiation therapy in 47%, and were 52%, 38%, 46%, respectively, in the TAM + CYP2D6 inhibitor group. Among women on a CYP2D6 inhibitor, the median duration of overlap with TAM was 255 days. Patients receiving TAM + a CYP2D6 inhibitor had a 2-year BrCa recurrence rate of 13.9% versus 7.5% in patients receiving TAM alone (HR 1.92, 95% CI 1.33–2.76, p < 0.001). Conclusions: Our findings support the presence of a clinically significant drug interaction between TAM and known CYP2D6 inhibitors. This resulted in a significant 1.9 fold higher BrCa recurrence within 2 years of initiating TAM therapy. [Table: see text]

scholarly journals Survey to describe variability in early onset scoliosis cast practices

2018 ◽  
Vol 12 (4) ◽  
pp. 406-412 ◽  
Author(s):  
A. Grzywna ◽  
A. McClung ◽  
J. Sanders ◽  
P. Sturm ◽  
L. Karlin ◽  
...  
Keyword(s):  
Early Onset ◽  
Congenital Scoliosis ◽  
Patient Characteristics ◽  
Study Groups ◽  
Early Onset Scoliosis ◽  
Radiographic Evaluation ◽  
Level Of Evidence ◽  
Major Curve ◽  
Radiographic Measurements ◽  
Multicentre Research

Purpose To investigate paediatric orthopaedists’ cast practices for early onset scoliosis regarding patient selection, cast application, radiographic evaluation, treatment cessation and adjunctive bracing. Methods A casting survey was distributed to all paediatric orthopaedists in Children’s Spine and Growing Spine Study Groups (n = 92). Questions included physician and patient characteristics, technique, treatment, outcomes, radiographic measurements and comparison to other treatments. A total of 55 orthopaedists (60%) responded, and descriptive statistics were calculated on the subset who cast (n = 45). Results A majority of respondents use cast treatment for idiopathic and syndromic scoliosis patients, but not for neuromuscular or congenital scoliosis patients. Major curve angle ranked most important in orthopaedists’ decision to commence cast treatment, in comparison with rib-vertebra angle difference or clinical observations. The major curve angle threshold to initiate casting was a median of 30° (20° to 70°), and the minimum patient age was median ten months (3 to 24). First in-cast and out-of-cast radiographs are taken standing, supine, awake, under anesthesia and/or in traction. In all, 58% consistently cast over or under the arm, while 44% vary position by patient. Respondents were divided about the use of a brace after cast treatment: 22% do not prescribe a brace, 31% always do and 36% do in some patients. Conclusions Future multicentre research studies must standardize radiographic practices and consider age and major curve angle at cast initiation and termination, scoliosis aetiology, shoulder position and treatment duration. Practices need to be aligned or compared in these areas in order to distinguish what makes for the best cast treatment possible. Level of Evidence V, Expert opinion

Association between acute ischemic stroke etiology and macroscopic aspect of retrieved clots: is a clot’s color a warning light for underlying pathologies?

2019 ◽  
Vol 11 (12) ◽  
pp. 1197-1200 ◽  
Author(s):  
Alessandro Sgreccia ◽  
Zoé Duchmann ◽  
Jean Philippe Desilles ◽  
Bertrand Lapergue ◽  
Julien Labreuche ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Infective Endocarditis ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Case Reports ◽  
Patient Characteristics ◽  
Study Groups ◽  
Double Blind ◽  
Stroke Etiology

BackgroundFew case reports have considered the chromatic aspect of retrieved clots and the possible association with their underlying etiology.ObjectiveThe aim of our study was to analyze the frequency of the TOAST ischemic stroke typical (atrial fibrillation, dissection, atheroma) and atypical (infective endocarditis, cancer-related, valve-related thrombi) etiologies depending on the chromatic aspect of retrieved clots.MethodsA total of 255 anonymized and standardized clot photos of consecutive patients treated by mechanical thrombectomy for acute ischemic stroke were included. A double-blind evaluation was performed by two senior interventional neuroradiologists, who classified the visual aspects of the clots into two main patterns: red/black or white. Main patient characteristics, distribution of underlying stroke etiologies, and outcomes were compared between the two study groups.ResultsThe inter-reader agreement for clot colors was excellent (k=0.78). Two hundred and thirty-three patients were classified as having red/black clots and 22 as having white clots. A statistically significant association (p=0.001) between atypical etiologies and white clots was observed.ConclusionsWhite clots were significantly associated with atypical etiologies in this cohort,in particular, with infectious endocarditis.

scholarly journals Direct Oral Anticoagulants in Atrial Fibrillation Patients With Concomitant Hyperthyroidism

2020 ◽  
Vol 105 (9) ◽  
pp. 2893-2904
Author(s):  
Yi-Hsin Chan ◽  
Lung-Sheng Wu ◽  
Lai-Chu See ◽  
Jia-Rou Liu ◽  
Shang-Hung Chang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Lower Risk ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Study Groups ◽  
Research Database ◽  
Nonvalvular Atrial Fibrillation ◽  
Asian Patients

Abstract Objective Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44–0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43–0.86; P = 0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.

scholarly journals Three handy tips and a practical guide to improve your propensity score models

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000953 ◽  
Author(s):  
Sytske Anne Bergstra ◽  
Alexandre Sepriano ◽  
Sofia Ramiro ◽  
Robert Landewé
Keyword(s):  
Real World ◽  
Observational Studies ◽  
Propensity Scores ◽  
Patient Characteristics ◽  
Confounding By Indication ◽  
Real World Data ◽  
Treatment Allocation ◽  
Popular Method ◽  
Clinical Scenarios ◽  
Treatment Responses

Real-world data are increasingly available to investigate ‘real-world’ safety and efficacy. However, since treatment in observational studies is not randomly allocated, confounding by indication may occur, in which differences in patient characteristics may influence both treatment choices and treatment responses. A popular method to adjust for this type of bias is the use of propensity scores (PS). The PS is a score between 0 and 1 that reflects the likelihood per patient of receiving one of the treatment categories of interest conditional on a set of variables. At least in theory, in patients with similar PS, the treatment prescribed will be independent of these variables (pseudorandomisation). But researchers using PS sometimes fail to recognise important methodological flaws which can lead to spurious conclusions. These include perfect prediction of treatment allocation, untied observations and lack of generalisability due to oversimplification of complex clinical scenarios. In this viewpoint we will discuss the most commonly encountered flaws and provide a stepwise description on the estimation and use of PS, such that in future publications these flaws can be avoided.

Revised International Prognostic Index (R-IPI) Is a Better Predictor of Outcome Than the Standard IPI for Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab and CHOP (R-CHOP).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 492-492 ◽  
Author(s):  
Laurie H. Sehn ◽  
Mukesh Chhanabhai ◽  
Catherine Fitzgerald ◽  
Karamjit Gill ◽  
Paul Hoskins ◽  
...  
Keyword(s):  
Overall Survival ◽  
International Prognostic Index ◽  
Young Patients ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Research Database ◽  
Clinical Tool ◽  
Field Radiation

Abstract Background: The IPI, which was developed prior to the availability of rituximab, remains the primary clinical tool used to predict outcome for patients with DLBCL. Since clinical trials investigating the use of rituximab and chemotherapy in this patient population have been confined to either elderly or young patients exclusively, the utility of the IPI in the era of immuno-chemotherapy remains unknown. Methods: We performed a retrospective analysis to assess the predictive value of the IPI in an unselected population of patients with DLBCL treated with R-CHOP. Patients were identified using the Lymphoid Cancer Research Database of the British Columbia (BC) Cancer Agency. We included all patients ≥16 years of age who were newly diagnosed with DLBCL prior to Jan 15, 2005, and were treated in BC with an R-CHOP protocol. Patients were excluded if they were HIV positive, had evidence of an active second malignancy or an underlying indolent lymphoma. Results: 365 patients were identified. Patient characteristics were as follows: median age 61 y (16–90); male, 61%; advanced stage III/IV, 59%; elevated LDH, 54%; PS≥2, 40%; &gt;1 extranodal site, 35%. Central pathology review was performed on 95% of patients; 324 DLBCL, 36 PMBCL, 5 other. All patients received R-CHOP; 9% were treated with R-CHOP x 3 and involved field radiation therapy for limited stage disease, remaining patients received 6–8 cycles of R-CHOP. Median follow-up for living patients is 22 months. Overall, the IPI remains predictive for both progression-free survival (p&lt;0.0001) and overall survival (p&lt;0.0001). However, the IPI no longer permits separation between the two low risk subgroups (low v low-intermediate) or between the two high risk subgroups (high-intermediate v high). (see Table) An alternate grouping of the IPI is proposed (R-IPI) that identifies three distinct prognostic groups. (see Table and Figure) Conclusions: The IPI remains predictive in the era of immuno-chemotherapy, but the R-IPI provides a simplified and more accurate prediction of outcome. The IPI factors can no longer be used to identify a group with less than a 50% chance of survival. Overall Survival According to Revised IPI (R-IPI) Overall Survival According to Revised IPI (R-IPI)

Compliance and persistency with imatinib

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6038-6038 ◽  
Author(s):  
W. Feng ◽  
H. Henk ◽  
S. Thomas ◽  
J. Baladi ◽  
A. Hatfield ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Multivariate Analyses ◽  
Medication Possession Ratio ◽  
Patient Characteristics ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
First Year ◽  
Optimal Dosing ◽  
Medical Benefits ◽  
N 93

6038 Background: Imatinib is an oral therapy with efficacy in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). Optimal dosing and adherence to treatment is critical to achieve the best clinical outcomes. This study examined compliance and persistency with imatinib and identified the clinical and patient characteristics related to compliance. Methods: Claims data from a US health plan were used to identify imatinib-treated patients from 6/1/01–3/31/04 who had continuous pharmacy and medical benefits in the 3 months prior and 12 months following initiation of imatinib therapy, and a diagnosis of CML or GIST (ICD-9-CM 205.1, 205.10, or 205.11 for CML; 159.0, 159.8, or 159.9 for GIST). Compliance was defined by medication possession ratio (MPR = total days supply of imatinib in the first year divided by 365). Persistency was defined as failure to refill imatinib within 30 days from the run-out date of the prior prescription. Multivariate analyses were used to identify key factors associated with compliance. Results: Total 878 imatinib-treated patients were identified of whom 413 had at least 15 months’ continuous eligibility. Sixty-nine percent (n = 286) were diagnosed with CML, 8% (n = 34) with GIST, and 23% (n = 93) with neither. Results are presented for CML and GIST patients. The average age was 51 and 58% were males. The average starting daily dose was 424 mg, with 80% (n = 255) initiating on 400 mg daily. The mean MPR was 76%. Overall, 28% patients discontinued imatinib for at least 30 consecutive days during the 1-year follow up period. Multivariate analyses indicated MPR improved with age until age 51 and then deteriorated (p < 0.001) but at a diminishing rate, decreased as the number of medications increased (p < 0.001), and was lower in women (p = 0.005) and patients with more cancer complications (p < 0.001). In addition, women were more likely to discontinue than men (OR = 2.08; p = 0.003). Conclusions: Compliance to imatinib was about 75% with 30% of patients interrupting therapy for at least 30 consecutive days in the first year. It has been found that interruption of imatinib therapy may lead to rapid tumor progression in GIST (PASCO05 Le Cesne #9031). Not having patients take the correct doses on a regular basis may lead to sub therapeutical clinical outcomes. [Table: see text]

Phase 2 study of the CDK4 inhibitor abemaciclib in dedifferentiated liposarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11004-11004 ◽  
Author(s):  
Mark Andrew Dickson ◽  
Andrew Koff ◽  
Sandra P. D'Angelo ◽  
Mrinal M. Gounder ◽  
Mary Louise Keohan ◽  
...  
Keyword(s):  
Partial Response ◽  
Primary Endpoint ◽  
Study Drug ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Cancer Center ◽  
Phase 2 ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
Cdk4 Inhibitor

11004 Background: The oncogene cyclin-dependent kinase 4 (CDK4) is amplified in > 90% of de-differentiated liposarcomas (DDLS). We previously demonstrated that treatment with the CDK4 inhibitor palbociclib results in favorable progression-free survival (PFS) in DDLS. Abemaciclib is a newer and more potent CDK4 inhibitor. This single-arm phase 2 study was designed to test the activity of abemaciclib in DDLS. Methods: Participants were adults with advanced DDLS, measurable disease by RECIST 1.1, any (or no) priory therapy, and progression by RECIST in the 6 months prior to study entry. The primary endpoint was PFS at 12 weeks. Based on historical data, promising drugs have 12-week PFS of ≥ 40% and not promising ≤ 20%. This study would be positive if 12-week PFS was ≥ 60%. The study was approved by the Institutional Review Board of Memorial Sloan-Kettering Cancer Center and all patients provided written informed consent. The study was registered at Clinicaltrials.gov (NCT02846987) and study drug was provided by Eli-Lilly. Results: Treatment was abemaciclib 200 mg by mouth twice daily continuously. 30 patients were treated and 29 were evaluable for the primary endpoint. Patient characteristics: Median age 62 (range 39-88), 60% male. Lines of prior therapy: 0 (50%); 1 (33%); ≥ 2 (17%). The observed PFS at 12 weeks was 76% (95% CI 57-90%). Median PFS was 30.4 weeks (95% CI 28.9-NE). There was one partial response. A further 3 patients had > 10% decrease in tumor size by RECIST but did not meet the criterion for partial response. Grade 3-4 toxicity included anemia (37%), neutropenia (20%), thrombocytopenia (17%) and diarrhea (7%). Conclusions: This study met its primary endpoint. In patients with advanced progressive DDLS, abemaciclib treatment results in favorable PFS and objective tumor response with manageable toxicity. Updated response data and results of paired tumor biopsies will be presented. Clinical trial information: NCT02846987.

Increased risk of urinary calculi in patients with migraine: A nationwide cohort study

Cephalalgia ◽  
2014 ◽  
Vol 35 (8) ◽  
pp. 652-661 ◽  
Author(s):  
Min-Juei Tsai ◽  
Yung-Tai Chen ◽  
Shuo-Ming Ou ◽  
Chia-Jen Shin ◽  
Kuan-Po Peng ◽  
...  
Keyword(s):  
Cohort Study ◽  
Propensity Scores ◽  
Urinary Calculi ◽  
Research Database ◽  
Unresolved Issue ◽  
Control Cohort ◽  
Increased Risk ◽  
Taiwan National Health Insurance ◽  
Annual Frequency ◽  
Clinic Visits

Objective Whether migraine is associated with urinary calculi is an unresolved issue, although topiramate, a migraine-preventive agent, is known to contribute to this complication. This study investigates the association between migraine and the risk of urinary calculi. Methods We identified a total of 147,399 patients aged ≥18 years with migraine diagnoses recorded in the Taiwan National Health Insurance Research Database between 2005 and 2009. Each patient was randomly matched with one individual without headache using propensity scores. All participants were followed from the date of enrollment until urinary calculi development, death, or the end of 2010. Results The risk of urinary calculi was greater in the migraine than the control cohort (adjusted hazard ratio (aHR), 1.58; 95% confidence interval (CI), 1.52–1.63; p < 0.001, irrespective of the influence of topiramate. The risk was higher in younger and female patients. The magnitude of the risk was proportional to the annual frequency of clinic visits for headache (≥6 vs. <3, aHR = 1.11; 95% CI, 1.04–1.17; p = 0.002), but did not differ between migraine patients with and without aura. Conclusions Our study showed migraine was associated with an increased risk of urinary calculi, independent of topiramate use. A higher frequency of clinic visits was associated with a greater risk.

scholarly journals Effectiveness, Safety, and Major Adverse Limb Events in Atrial Fibrillation Patients with Concomitant Diabetes Mellitus Treated with Non-Vitamin K Antagonist Oral Anticoagulants

2020 ◽  
Author(s):  
Yi-Hsin Chan ◽  
Hsin-Fu Lee ◽  
Pei-Ru Li ◽  
Jia-Rou Liu ◽  
Tze-Fan Chao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Vitamin K ◽  
Lower Risk ◽  
Oral Anticoagulants ◽  
Study Groups ◽  
Vitamin K Antagonist ◽  
Major Adverse Cardiovascular Events ◽  
Research Database ◽  
Atherosclerotic Burden

Abstract Background: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5,812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. Results: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI):0.78-0.99]; P =0.0283), major adverse limb events (aHR:0.72;[95%CI:0.57-0.92]; P =0.0083), and major bleeding (aHR:0.67;[95%CI:0.59-0.76]; P <.0001) compared to warfarin. NOACs decreased MACE in patients of 75 but not in those aged <75 years ( P interaction=0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD ( P interaction<0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. Conclusion: NOACs were associated with a lower risk of effectiveness, safety, and major adverse limb events than warfarin among diabetic AF patients. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Sign in / Sign up

Export Citation Format

Share Document