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How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

ABSTRACT: Despite an increasing desire to use historical cohorts as "synthetic" controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012-2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

SUBMITTER: Tiong IS

PROVIDER: S-EPMC10965987 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

Tiong Ing Soo IS Wall Meaghan M Bajel Ashish A Kalro Akash A Fleming Shaun S Roberts Andrew W AW Thiagarajah Nisha N Chua Chong Chyn CC Latimer Maya M Yeung David D Marlton Paula P Johnston Amanda A Enjeti Anoop A Fong Chun Yew CY Cull Gavin G Larsen Stephen S Kennedy Glen G Schwarer Anthony A Kipp David D Ramanathan Sundra S Verner Emma E Tiley Campbell C Morris Edward E Hahn Uwe U Moore John J Taper John J Purtill Duncan D Warburton Pauline P Stevenson William W Murphy Nicholas N Tan Peter P Beligaswatte Ashanka A Mutsando Howard H Hertzberg Mark M Shortt Jake J Szabo Ferenc F Dunne Karin K Wei Andrew H AH

Blood cancer journal 20240326 1

Despite an increasing desire to use historical cohorts as "synthetic" controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecula ...[more]

PMID: 38531863

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Project description:BackgroundPatients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real-world psoriasis population.ObjectivesFirstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real-world populations of patients on biologic therapies for psoriasis using a standardization method.MethodsData from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant-level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C-statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting.ResultsIn total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C-statistic of 0.82 [95% confidence interval (CI) 0.81-0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI < 1.5 were 9.27 (95% CI -3.91-22.5) per 1000 person-years and 0.95 (95% CI -1.98-4.15), respectively.ConclusionsOur results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real-world population, but this lack of external validity does not account for the efficacy-effectiveness gap. What's already known about this topic? Patients with psoriasis who would not be eligible for randomized controlled trials (RCTs) investigating biologic therapies have a greater risk of serious adverse events and lower treatment effectiveness than patients who would have been eligible. What does this study add? Baseline patient characteristics were shown to be predictive of whether a patient would have been eligible for enrolment in an RCT for psoriasis biologic therapy. We did not find any efficacy-effectiveness gap between the sample representative of the real-world population of patients with psoriasis and the sample representative of the RCT population. Factors outside of baseline patient characteristics, such as observer effect and higher adherence in RCTs, may be more influential in any efficacy-effectiveness gap between trial and real-world populations of patients with psoriasis.

Project description:This study describes how health care providers approach canagliflozin for the treatment of patients with type 2 diabetes mellitus (T2DM) in the real world.An Internet-based questionnaire was completed by 101 endocrinologists, 101 primary care physicians, and 100 nurse practitioners/physician assistants (NP/PAs). Health care providers were required to have experience prescribing or managing patients using canagliflozin to be included in the study. Health care providers compared canagliflozin with other T2DM medication classes on clinical characteristics, costs, and patient satisfaction. Confidence in canagliflozin was also measured. Health care providers reported their canagliflozin prescribing experience and good candidate characteristics for treatment. Finally, providers reported on patient outcomes among those receiving canagliflozin. All variables were compared across provider type.Health care providers reported higher favorability for canagliflozin for blood pressure and body weight compared with dipeptidyl peptidase-4 (DPP-4) inhibitors and higher favorability for effect on blood pressure, body weight, treatment satisfaction, and glycosylated hemoglobin (HbA1c) compared with sulfonylureas (SUs), with differences observed for effect on blood pressure. Health care providers reported being very/extremely confident (55%-74%) with canagliflozin as a second-to fourth-line treatment. The top 3 characteristics reported by the providers, in terms of describing a good candidate for canagliflozin, include those concerned about their weight, insurance coverage/affordability, and avoiding injectable treatments. Finally, providers reported often/always observing patients' lowering or controlling HbA1c (82%-88%) and improvement in overall quality of life (QoL; 50%-53%) with canagliflozin treatment. No differences were observed across provider type for confidence, good candidate characteristics, or patient outcomes.Health care providers reported favorable experiences with canagliflozin and witnessed improvements in patients' clinical outcomes and QoL.

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Project description:Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out-of-pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01-6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03-2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08-19.12; p = 0.00). Remembering to take the medication was a significant predictor of self-reported adherence (OR = 16.66; 95% CI, 3.30-84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self-reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Dataset Information

How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

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How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

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