Real-World Evidence: Bridging Gaps in Evidence to Guide Payer Decisions

Roberts, Melissa H.; Ferguson, Gary T.

doi:10.1007/s41669-020-00221-y

Cited by 32 publications

(36 citation statements)

References 79 publications

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“…Further, Gleason scores tended to be lower in the RCTs compared to the present study population (i.e., Gleason scores C 8: * 50 vs. 66% of patients) [40,41]. Finally, patients in RCTs generally show better adherence, persistence, and compliance to therapy [43,44], which may have also contributed to the longer duration of NHA treatment compared to real-world studies. Future studies should further elucidate the shorter duration of NHA treatment in realworld studies compared with RCTs.…”

Section: Discussionmentioning

confidence: 69%

“…As more patients receive NHA in the earlier settings, the treatment patterns and subsequent time on treatment will likely evolve. Second, longer treatment durations in RCTs may also reflect the inclusion of patients with less severe disease compared to real-world populations [43,44]. Consistent with this, some RCTs of the safety and efficacy of NHA had selected patients that were treatment-naïve and asymptomatic or minimally symptomatic with lower ECOG performance status (e.g., scores B 1) [39,42], while other RTCs had excluded patients with serious nonmalignant comorbidities [41].…”

Section: Discussionmentioning

confidence: 99%

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Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors

et al. 2021

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Introduction: Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) patients are continuously advancing. We described mCRPC treatment patterns in the US from 2013 to 2019. Methods: Patients with a confirmed mCRPC diagnosis and adenocarcinoma histology were included in the US Flatiron Health Electronic Health Record-derived de-identified database. Treatment patterns [including treatment per lines of therapies (LOTs), LOT sequences, and time on treatment] and overall survival (OS) have been described in mCRPC settings. Results: Of 5213 patients (mean age: 72.6 years), 4374 (83.9%) were treated with C 1 LOT post-mCRPC diagnosis (among those with C 1 LOT, 55.3%, 29.5%, 14.7%, and 6.7% had C 2, 3, 4, and 5 LOTs, respectively). In first line (1L), the main treatment class was nextgeneration hormonal agents (NHA; 62.5% of patients with C 1 LOT), while the shortest and longest time on 1L were observed for chemotherapy (median 2.8 months) and NHA (median 5.1 months), respectively. The most common LOT sequences were NHA ? NHA (29.4% of patients with C 2 LOTs) and NHA ? NHA ? chemotherapy (16.7% of patients with C 3 LOTs). In Kaplan-Meier analyses, the median OS was 19.4, 14.6, and 11.1 months post-1L, 2L, and 3L start, respectively. Patients who moved rapidly through LOTs had an increased risk of death. Conclusions: NHA were widely used as 1L therapy in mCRPC patients from 2013 to 2019, but time on 1L NHA treatment was on aver-age\6 months. While NHA ? NHA was the most observed 1L ? 2L LOT sequence, a plethora of other LOT sequences were observed. OS was poor, highlighting an unmet need for lifeprolonging treatments.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors

et al. 2021

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“…Although clinical trials should provide the highest level of evidence to guide therapeutic decisions, to date, there is a lack of head-to-head comparisons on the different GLP-1 RA molecules [ 14 ]. Furthermore, the results of real-world studies are sometimes contradictory, because of small sample sizes, differences in statistical and laboratory methodologies, or participants’ heterogeneity [ 44 ]. As a secondary aim of the study, we compared the long-term effectiveness of DU to that of LIRA, by analyzing two patient cohorts who were highly similar for baseline characteristics, including background medications.…”

Section: Discussionmentioning

confidence: 99%

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

Mirabelli

Chiefari

Tocci

et al. 2021

JCM

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Aims and methods: The aim of this monocentric retrospective observational study was to evaluate the 18-month safety and effectiveness of GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) 1.5 mg/once weekly as an add-on to metformin (MET) or MET plus conventional insulin secretagogues in a study cohort with excess body weight and type 2 diabetes (T2D). Comparative efficacy versus liraglutide (LIRA) 1.2–1.8 mg/once daily in a study sample naïve to GLP-1 RAs, frequency matching for age, gender, T2D duration, degree of glycemic impairment, cardiovascular comorbidities, and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Results: Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate–severe gastrointestinal AEs after a mean follow-up of 6 (4 standard deviations (SD)) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant mean HbA1c reduction of −0.85% (1.17 SD) with respect to baseline values (p < 0.001), which remained stable during 18 months follow-up. These results were accompanied by a moderate weight loss sustained over time, with a mean reduction of −2.0% (4.3 SD) at 6 months and −1.3% (4.8 SD) at 18 months (p = 0.091). At univariate analysis, a negative correlation between baseline body mass index (BMI) and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity against drug discontinuation was confirmed by logistic regression analysis. Neither gender, nor age, nor T2D duration, nor concomitant conventional insulin secretagogue use, nor switching to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in terms of HbA1c reduction ≥ 0.5% or body weight loss ≥ 5%. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and body weight in real-world experiences. With the advantage of once-weekly administration, at 18-month follow-up, a significantly larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p = 0.033). Conclusions: Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial responses to DU on a background of MET or MET plus insulin secretagogues are durable, especially in the presence of obesity and greater HbA1c impairment.

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“…1,2 However, the risk of bias 3 in nonrandomized studies can pose a threat to their validity even when statistical methods to reduce confounding due to lack of treatment randomization are used, which has made HTA agencies reluctant to use them in their decision-making. 4,5 For example, RWD often contain significant amounts of missing observations for important prognostic variables that are not uniformly recorded in routine clinical practice, such as Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) in cancer studies. 6 Findings from such studies can be prone to bias if assumptions about the mechanism of missingness are incorrectly specified or if unmeasured confounders are not accounted for.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

et al. 2021

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IMPORTANCE Quantitative assessment of bias from unmeasured confounding and missing data can help evaluate uncertainty in findings from indirect comparisons using real-world data (RWD).OBJECTIVE To compare the effectiveness of alectinib vs ceritinib in terms of overall survival (OS) in patients with ALK-positive, crizotinib-refractory, non-small cell lung cancer (NSCLC) and to assess the sensitivity of these findings to unmeasured confounding and missing data assumptions. DESIGN, SETTING, AND PARTICIPANTSThis comparative effectiveness research study compared patients from 2 phase 2 alectinib trials and real-world patients. Patients were monitored from June 2013 to March 2020. Comparisons of interest were between alectinib trial data vs ceritinib RWD and alectinib RWD vs ceritinib RWD. RWD treatment groups were selected from nationally representative cancer data from US cancer clinics, the majority from community centers. Participants were ALK-positive patients aged 18 years or older with advanced NSCLC, prior exposure to crizotinib, and Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2. Data analysis was performed from October 2020 to March 2021. EXPOSURES Initiation of alectinib or ceritinib therapy. MAIN OUTCOMES AND MEASURESThe main outcome was OS. RESULTSIn total, there were 355 patients: 183 (85 men [46.4%]) in the alectinib trial, 91 (43 men [47.3%]) in the ceritinib RWD group, and 81 (38 men [46.9%]) in the alectinib RWD group. Patients in the alectinib trial were younger (mean [SD] age, 52.53 [11.18] vs 57.97 [11.71] years), more heavily pretreated (mean [SD] number of prior therapy lines, 1.95 [0.72] vs 1.47 [0.81]), and had more favorable baseline ECOG PS (ECOG PS of 0 or 1, 165 patients [90.2%] vs 37 patients [77.1%]) than those in the ceritinib RWD group. The alectinib RWD group (mean [SD] age, 58.69 [11.26] years) had more patients with favorable ECOG PS (ECOG PS of 0 or 1, 49 patients [92.4%] vs 37 patients [77.1%])and more White patients (56 patients [72.7%] vs 53 patients [62.4%]) compared with the ceritinib group. Compared with ceritinib RWD, alectinib-exposed patients had significantly longer OS in alectinib trials (adjusted hazard ratio [HR], 0.59; 95% CI, 0.44-0.75; P < .001) and alectinib RWD (HR, 0.46; 95% CI, 0.29-0.63; P < .001) after adjustment for baseline confounders. For the worst-case HR estimate of 0.59, residual confounding by a hypothetical confounder associated with mortality and treatment by a risk ratio greater than 2.24 was required to reverse the findings. Conclusions were robust to plausible deviations from random missingness for missing ECOG PS and underrecorded comorbidities and central nervous system metastases in RWD. CONCLUSIONS AND RELEVANCEAlectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC, and only substantial levels of bias examined reversed (continued)

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Real-World Evidence: Bridging Gaps in Evidence to Guide Payer Decisions

Cited by 32 publications

References 79 publications

Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors

Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

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