Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Background: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT. Objectives: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns. Design: This is a cross-sectional survey study. Methods: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns. Results: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT. Conclusion: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.

Background and aims: Fecal microbiota transplantation (FMT) is a promising new treatment for active ulcerative colitis. Questions remain around the benefits and risks of FMT treatment for patients with ulcerative colitis. Understanding how patients weigh the treatment features and how treatment features influence their decisions may improve shared decision-making and contribute to patient-centered care, which is especially important for novel treatments like FMT.Using an experimentally designed survey, we aimed to:1. Elicit patient preferences for features of active ulcerative colitis treatments, specifically FMT and biologics; and,2. Identify patient characteristics associated with different preference patterns. Results: We found that younger patients with more severe disease are more likely to try FMT for the treatment of active ulcerative colitis. Oral capsules/pills are the preferred mode of treatment administration. Conclusions: These findings can enhance patient-centered care by characterizing patients who are more likely to be interested in FMT. Aligning treatment with the features that are important to patients can potentially improve satisfaction with and adherence to treatments for active ulcerative colitis to maximize their effectiveness for individual patients.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Cost-efficiency and budget-neutral expanded access modeling of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIMS: To estimate, in the setting of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) for an assumed 1,207 incident US cases in 2024, (1) the cost-efficiency of a toripalimab-gemcitabine-cisplatin regimen compared to a similar pembrolizumab regimen; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens afforded by the accrued savings. METHODS: Simulation modeling utilized two cost inputs (wholesale acquisition cost (WAC) at market entry and an ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) and drug administration costs over 1 and 2 years of treatment with treatment rates ranging from 45% to 90%. In the absence of trial data for pembrolizumab-gemcitabine-cisplatin in R/M NPC, it is assumed that such a regimen would be comparable to toripalimab-gemcitabine-cisplatin in efficacy and safety. RESULTS: In the models utilizing the WAC, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 1,207-patient panel, estimated 1-year savings range from $21,733,702 (45% treatment rate) to $43,467,404 (90% rate). Reallocating these savings permits budget-neutral expanded access to an additional 2,359 (45% rate) to 4,717 (90% rate) toripalimab maintenance cycles or to an additional 126 (45% rate) to 252 (90%) full 1-year toripalimab regimens with all agents. Two-year savings range from $42,259,976 (45% rate) to $84,519,952 (90% rate). Reallocating these efficiencies provides expanded access, ranging from an additional 4,586 (45% rate) to 9,172 (90% rate) toripalimab cycles or to an additional 128-257 full 2-year toripalimab regimens. The ex ante ASP model showed similar results. CONCLUSION: This simulation demonstrates that treatment with toripalimab generates savings that enable budget-neutral funding for up to an additional 252 regimens with toripalimab-gemcitabine-cisplatin for one full year, the equivalent of approximately 21% of the 2024 incident cases of R/M NPC in the US.

An estimated 1,207 patients will be diagnosed with late-stage nasopharyngeal cancer in the US in 2024. Toripalimab is a novel PD-1 inhibitor drug approved by the US Food and Drug Administration on October 27, 2023 as first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer when used in combination with gemcitabine and cisplatin. We conducted economic evaluations of the costs of this toripalimab regimen versus the costs of a similar regimen with the PD-1 inhibitor pembrolizumab. Our simulation models used two pricing scenarios: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, an estimated toripalimab price point of 80% of the pembrolizumab ASP. We compared the savings in each scenario when between 45% and 90% of the 1,207 patients are treated with the toripalimab regimen. We then evaluated how these savings could be re-allocated, on a budget-neutral basis and without requiring extra cash outlays, to provide more patients with access to toripalimab treatment; specifically, how many toripalimab doses and how many full toripalimab regimens could be purchased to provide more patients with treatment. We found that, if 90% of new cases of recurrent or metastatic nasopharyngeal cancer were treated with toripalimab over 1 year, these savings are enough to purchase up to 4,717 additional doses on a budget-neutral basis, which could provide up to an additional 252 newly diagnosed patients with 1 year of treatment with toripalimab. In combination with gemcitabine and cisplatin, toripalimab can markedly improve access to care for patients with recurrent or metastatic nasopharyngeal cancer in a cost-responsible way.

Multicenter matched-pair study comparing BACT/ALERT® MP reagent systems for the recovery of mycobacteria from specimens other than blood.

The BACT/ALERT® MP Reagent System is a broth culture medium for optimal detection and recovery of mycobacteria from clinical samples. The MP formulation was recently modified to improve detection and recovery times. A multicenter prospective matched pair study design was conducted to validate the performance of improved MP (MP-I) versus current MP (MP-C) bottles utilizing nonsterile and normally sterile samples, except blood, from patients suspected of having mycobacterial infections. A total of 1488 clinical samples were collected to obtain 212 mycobacteria samples by either or both MP culture bottles. MP-I and MP-C sensitivities were 86.6% and 81.4%, respectively, but the difference was not significant (P = 0.163) while specificities were 96.8% and 93.8%, respectively, and that difference was significant (P = 0.002). Overall recovery was 94.34% for MP-I and 88.68% for MP-C (recovery was 100% for both bottles with 52 seeded samples). Overall performance of MP-I was better than MP-C for sensitivity, specificity, and recovery.

Are We Capturing the Socioeconomic Burden of Rare Genetic Disease? A Scoping Review of Economic Evaluations and Cost-of-Illness Studies.

BACKGROUND AND OBJECTIVES: Rare diseases have a significant impact on patients, families, the health system, and society. Measuring the socioeconomic burden is crucial to valuing interventions for rare diseases. Healthcare system costs are significant, but so are costs to other government sectors, patients, families, and society. To understand the breadth of costs captured in rare disease studies, we examined the cost categories and elements of socioeconomic burden captured in published studies. METHODS: A scoping review was conducted using five electronic databases to identify English language economic evaluations and cost-of-illness studies of interventions for rare diseases (2011-21). We mapped costs using a previously developed evidence-informed framework of socioeconomic burden costs for rare disease. RESULTS: Of 4890 studies identified, 48 economic evaluations and 22 cost-of-illness studies were included. While 18/22 cost-of-illness studies utilized a societal perspective, only 7/48 economic evaluations incorporated societal costs. Most reported cost categories related to medical costs, with medication and hospitalizations being the most common elements for both study designs. Costs borne by patients, families, and society were reported less among economic evaluations than cost-of-illness studies. These included: productivity (10% vs 77%), travel/accommodation (6% vs 68%), government benefits (4% vs 18%), and family impacts (0% vs 50%). CONCLUSIONS: Contrary to cost-of-illness analyses, most of the included economic evaluations did not account for the hidden burden of rare diseases, that is, costs borne by patients, families, and societies. Including these types of costs in future studies would provide a more comprehensive picture of the burden of disease, providing empirical data to inform how we value and make decisions regarding rare disease interventions, health policy, and resource allocation.

Developing a Framework of Cost Elements of Socioeconomic Burden of Rare Disease: A Scoping Review.

BACKGROUND AND OBJECTIVE: Rare diseases place a significant burden on patients, families, the healthcare system, and society. Evidence on the socioeconomic burden of rare disease is limited and mostly reflects diseases where treatments are available. We developed a framework encompassing recommended cost elements for studies of the socioeconomic burden of rare diseases. METHODS: A scoping review, conducted in five databases (Cochrane Library, EconLit, Embase, MEDLINE, and APA PsycINFO), identified English language publications from 2000 to 2021 presenting frameworks developed for determining, measuring or valuing costs for rare or chronic diseases. Cost elements were extracted and used to develop a literature-informed framework. Structured feedback was gathered from experts in rare diseases, health economics/health services, and policy research to revise the framework. RESULTS: Of 2990 records identified, eight papers were included and informed our preliminary framework; three focused on rare disease and five on chronic disease. Following expert input, we developed a framework consisting of nine cost categories (inpatient, outpatient, community, healthcare products/goods, productivity/education, travel/accommodation, government benefits, family impacts, and other), with several cost elements within each category. Our framework includes unique costs, added from the expert feedback, including genetic testing to inform treatment, use of private laboratories or out-of-country testing, family involvement in foundations and organizations, and advocacy costs for special access programs. CONCLUSIONS: Our work is the first to identify a comprehensive list of cost elements for rare disease for use by researchers and policy makers to fully capture socioeconomic burden. Use of the framework will increase the quality and comparability of future studies. Future work should focus on measuring and valuing these costs through onset, diagnosis, and post-diagnosis.

Impact of an online, individualised, patient reported outcome measures based patient decision aid on patient expectations, decisional regret, satisfaction, and health-related quality-of-life for patients considering total knee arthroplasty: Results from a randomised controlled trial.

RATIONALE: Total knee arthroplasty is a common surgical procedure but not appropriate for all patients with knee osteoarthritis. Patient decision aids (PtDAs) can promote shared decision making and enhance understanding and expectations of procedures among patients, resulting in better discussions between patients and healthcare providers about whether total knee arthroplasty is the most appropriate option. AIMS AND OBJECTIVES: Evaluate impact of an individualised PtDA for osteoarthritis patients considering total knee arthroplasty 1 year after baseline assessment. METHODS: Prospective, randomised controlled trial comparing an intervention arm (IA) and routine care arm (RCA). The IA included an online individualised patient reported outcome measures (PROMs) based PtDA and one-page summary report for the surgeon. We report secondary outcomes from the final assessment: patient expectations, decisional regret, patient satisfaction with outcomes of knee replacement, health-related quality-of-life (HRQOL) and depression. We report changes in HRQOL between baseline and final assessments, study arms, and surgical versus non-surgical patients. Descriptive statistics were used to describe participant characteristics and continuous variables. Dichotomous outcomes (expectations, decisional regret, satisfaction) were analyzed using logistic regression and continuous outcomes (HRQOL, depression) were modelled using linear regression. RESULTS: Overall, 140 participants completed all study assessments (IA: n = 69, RCA: n = 71); n = 108 underwent surgery (IA: n = 49, RCA: n = 59). Regardless of study arm, most participants reported expectations were met, minimal decisional regret, satisfaction with outcomes of knee replacement, and had improvements in HRQOL. While no significant differences in study outcomes were found between study arms, IA results were in the direction hypothesised in favour of the PtDA. CONCLUSIONS: Although we were not able to detect statistically significant benefits associated with implementing this PROMs-based PtDA, there was no apparent negative effect on these outcomes 1 year after baseline. We anticipate there may be benefit to implementing this PtDA earlier in the osteoarthritis care pathway where patients have more opportunities to manage their disease non-surgically.

An online individualised patient decision aid improves the quality of decisions in patients considering total knee arthroplasty in routine care: A randomized controlled trial.

Objective: The objective of this study was to evaluate the effectiveness of an online patient decision aid with individualised potential outcomes of surgery, on the quality of decisions for knee replacement surgery in routine clinical care. Design: A pragmatic Randomized Controlled Trial (RCT) in patients considering total knee replacement at a high-volume orthopedic clinic. Patients were randomized at their routine online pre-surgical assessment to either complete a decision aid or not. At their consultation, those in the intervention arm had a surgeon report summarizing the decision aid results. The primary outcome was decision quality, defined as being knowledgeable and choosing the option that matched informed treatment preferences. Multivariate logistic and linear regression analysis was conducted to consider surgeon level clustering and baseline differences between study arms. Results: Of 163 patients randomized, 155 completed post-surgical surveys and were included in the analysis. The average patient was aged 65 years, obese and had moderate to severe osteoarthritis symptoms at baseline. Patients in the intervention arm had a higher odds of making a quality decision (Odds Ratio â€‹= â€‹2.08, 95% CI: 1.08 to 4.02), predominantly through increased knowledge. Conclusions: This study supports the benefit of a decision aid in combination with a surgeon report to significantly improve decision quality in routine care. While the independent contribution of tailoring the decision aid to patient baseline characteristics and including a surgeon report remains unclear, we demonstrated the feasibility of integrating the decision aid into an online pre-surgical assessment in routine clinical care.

Patient Experiences in the Management of Inflammatory Bowel Disease: A Qualitative Study.

Background: Inflammatory bowel disease (IBD) can lead to substantial impairments of quality-of-life. Clinical guidelines and quality indicators aid physicians in practice but may not reflect the perspectives and experiences of patients with IBD. To address this, the objectives of this study were to understand patient experiences with IBD care and to explore priorities. Methods: Based on a convenience sample of 36 participants, five focus groups were completed at four sites across Canada. Data were analyzed using a deductive thematic analysis approach to assess emergent themes and variability in participants' experiences. Results: Our results are organized by themes of structure, process and outcomes to illustrate common issues with respect to how care is organized in the healthcare system, how patients receive and experience care and how patients perceive the outcomes of their care. Our results frame a health systems quality approach that signal needed improvements in access to care, the need for innovation with respect to virtual medicine, the potential expansion of multidisciplinary team-based care and the importance of addressing the psychosocial dimensions for patients with IBD and their caregivers in order to better deliver patient-centred care. Conclusions: The issues identified have the potential to impact priority areas in the system, IBD care delivery, and how outcomes can be improved by focusing on 'lived experience' and patient-centred care. The differing values and perspectives of all those involved in caring for patients with IBD underscore the importance of good communication with patients, caregivers and family members, as well as staying responsive to evolving needs.

Budget impact analysis of trilaciclib for decreasing the incidence of chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer in the United States.

BACKGROUND: Chemotherapy-induced myelosuppression, which commonly manifests as neutropenia, anemia, and/or thrombocytopenia, is a frequent and severe complication of standard treatment regimens for patients with extensive-stage small cell lung cancer (ES-SCLC). Trilaciclib is a first-in-class myeloprotective therapy indicated to decrease the incidence of chemotherapy-induced myelosuppression when administered prior to a platinum-/etoposide-containing regimen or topotecan-containing regimen for ES-SCLC. OBJECTIVE: To estimate the budget impact of administering trilaciclib prior to chemotherapy to manage chemotherapy-induced myelosuppression in adults with ES-SCLC from a US payer perspective. METHODS: A budget impact model was developed to assess the impact of introducing trilaciclib to a hypothetical 1 million-member health insurance plan. The model compared 2 market scenarios: a current scenario of standard treatments for ES-SCLC without trilaciclib, and an alternative scenario of standard treatment plus trilaciclib. Population, clinical, and cost inputs were derived from published literature and trilaciclib clinical trial data. Model outcomes included the number of myelosuppressive adverse events (AEs), costs of treatment, costs of AE management, total cost, and per-member per-month (PMPM) costs. The budget impact of trilaciclib was calculated as the difference in cost (2021 US dollars) between the 2 scenarios over a 1- to 5-year time horizon. Scenario and deterministic sensitivity analyses were conducted to assess uncertainty around key model inputs. RESULTS: An estimated total of 301 patients were eligible for treatment with trilaciclib over a 5-year period. The use of trilaciclib was estimated to reduce the number of myelosuppressive AEs over a 5-year period (events avoided included 108 for neutropenia, 7 for febrile neutropenia, 23 for anemia, and 46 for thrombocytopenia) compared with the scenario without trilaciclib. The adoption of trilaciclib was associated with a cost saving of $801,254 ($0.013 PMPM) over 5 years. The acquisition cost for trilaciclib ($3,704,199) was offset by the reduction in AE management cost ($4,282,748) and reduction in prophylactic granulocyte colony-stimulating factor use ($222,704). The cost savings associated with trilaciclib began in year 1 (total $34,388; $0.003 PMPM) and accrued over time. CONCLUSIONS: The acquisition cost of trilaciclib is projected to be offset by a reduction in the costs of managing AEs related to myelosuppression when added to standard chemotherapy regimens for ES-SCLC. The net budget impact of trilaciclib is estimated to be a cost saving. DISCLOSURES: This research was funded by G1 Therapeutics, Inc., and implemented by ZS Associates, an independent consultancy that collated the model inputs and performed the budget impact analysis. The study sponsor was involved in the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. The journal open access fee was funded by G1 Therapeutics, Inc. Moran, Chioda, and Huang are employed by G1 Therapeutics, Inc. Chioda and Huang report stocks and stock options for G1 Therapeutics, Inc. Goyal and Deniz are employed by ZS Associates. Goyal reports consulting fees from G1 Therapeutics, Inc. Abraham reports consulting fees from Coherus, G1 Therapeutics, Inc. (unrelated to this study and manuscript), Mylan/Viatris, and Sandoz and participation on a data safety monitoring board or advisory board for G1 Therapeutics, Inc. MacDonald reports consulting fees from Coherus, G1 Therapeutics, Inc. (unrelated to this study and manuscript), Mylan/Viatris, and Sandoz. Deniz reports no disclosures. A synopsis of the current study was presented in poster format at the Virtual AMCP Annual Meeting, April 12-16, 2021.

Reducing waiting lists for laparoscopic cholecystectomy: An intensive approach to aid COVID-19 recovery.

Background: Laparoscopic cholecystectomy is one of the most frequently performed operations in the United Kingdom, commonly due to symptomatic gallstones. Delay between diagnosis and definitive surgical intervention often leads to a significant readmission rate, growing financial burden and increased complexity of the ultimate surgical intervention. Resource reallocation and reduced operational capacity during the coronavirus disease 2019 (COVID-19) pandemic has led to an impending waiting list crisis. Methods: In an attempt to address the backlog of cases, five intensive dedicated operating lists were allocated for laparoscopic cholecystectomies across a weekend in October 2020 at a single Trust. Prospective data were collected to include baseline demographics, operative procedure, 30-day post-operative outcomes and financial implications. Results: A total of 21 cholecystectomies were performed in total, with a majority ASA 2 (American Society of Anaesthesiologists) for predominantly biliary colic indication. All were completed laparoscopically, with a 90.5% rate for complete resection. There were no reported on-table complications and 81.0% of patients discharged as a day case. Thirty day follow-up revealed a complication rate of 9.5%, with 2 patients requiring oral antibiotics for a superficial wound infection. The 30 day COVID-19 rate was 14.3%. Compared to completion on an average weekday list, the total weekend was estimated to have saved over £70,000 in overall costs. Conclusion: Our study showed that weekend focused operating, with a caveat of careful patient selection and high-quality multidisciplinary working, can be a feasible solution to long waiting lists due to COVID-19 pandemic. It was safe, with avoidance of increased burden on emergency resources, and significantly increased theatre efficiency.

Expanded access to anticancer treatments from conversion to biosimilar pegfilgrastim-cbqv in US breast cancer patients.

Aim: To estimate cost-savings from conversion to biosimilar pegfilgrastim-cbqv that could be reallocated to provide budget-neutral expanded access to AC (doxorubicin/cyclophosphamide) and TCH (docetaxel/carboplatin/trastuzumab) in breast cancer (BC) patients. Methods: Simulation modeling in panels of 20,000 BC and 5000 HER2+ (HER2+ BC) patients, varying treatment duration (one-six cycles) and conversion rates (10-100%), to estimate cost-savings and additional AC and TCH treatment that could be provided. Results: In 20,000 patients, cost-savings of $1,083 per-patient per-cycle translate to $21,652,064 (one cycle) to $129,912,397 (six cycles). Savings range from $5,413,016 to $32,478,097, respectively, in the 5000-patient HER2+ BC panel. Conclusion: Conversion to pegfilgrastim-cbqv could save up to $130 million and provide more than 220,000 additional cycles of antineoplastic treatment on a budget-neutral basis to BC patients.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. We calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 20,000 patients with breast cancer receiving chemotherapy with AC (doxorubicin/cyclophosphamide). We then computed the number of additional doses of AC chemotherapy that could be purchased with those savings. We did the same for a group of 5000 HER2+ breast cancer patients treated with TCH (docetaxel/carboplatin/trastuzumab). Using biosimilar pegfilgrastim could save $1,083 per patient per cycle. If all patients were treated with biosimilar pegfilgrastim over six cycles, $129.9 million could be saved in the AC group and $32.5 million in the TCH group. This could provide 220,468 additional AC doses and 6981 TCH doses. Biosimilar pegfilgrastim can generate significant savings. These savings can be used to provide additional patients with chemotherapy cost-free.

Meta-Analysis of Same-Day Pegfilgrastim Administration Stratified by Myelotoxic Febrile Neutropenia Risk and Tumor Type.

Background: Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Methods: Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. Conclusion: In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

Trilaciclib and the economic value of multilineage myeloprotection from chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer treated with first-line chemotherapy.

AIMS: Proliferating hematopoietic stem and progenitor cells (HSPCs) are susceptible to chemotherapy-induced damage, resulting in myelosuppressive adverse events (AEs) such as neutropenia, anemia, and thrombocytopenia that are associated with high health care costs and decreased quality of life (QoL). In this study, a trial-based cost-effectiveness analysis was performed to help assess the economic impact of administering trilaciclib, a myeloprotective therapy that protects multilineage HSPCs from chemotherapy-induced damage, prior to standard first-line chemotherapy, using data from a pivotal Phase II study of trilaciclib in the setting of extensive-stage small cell lung cancer (ES-SCLC, NCT03041311). METHOD: The aim of this study was to assess the cost-effectiveness of administering trilaciclib prior to chemotherapy versus chemotherapy alone among patients with ES-SCLC from a United States payer perspective. Data on the rate and frequency of myelosuppressive AEs and health utility were derived from the pivotal study of trilaciclib. Costs of managing myelosuppressive AEs and costs of chemotherapy treatment were sourced from published literature. Outcomes included the number of myelosuppressive AEs, costs (in 2021 US dollars), quality-adjusted life-years (QALYs), incremental cost, incremental QALY, and an incremental cost-effectiveness ratio. RESULTS: Administering trilaciclib prior to chemotherapy was associated with a reduction in neutropenia (82%), febrile neutropenia (75%), anemia (43%), and thrombocytopenia (96%) compared with chemotherapy alone. Additionally, trilaciclib prior to chemotherapy was cost-saving compared with chemotherapy alone ($99,919 vs $118,759, respectively) and associated with QALY improvement (0.150 vs 0.145, respectively). Probabilistic sensitivity analyses showed 58% of iterations projecting cost savings and QALY improvement with trilaciclib. CONCLUSIONS: The findings suggest that the use of trilaciclib prior to first-line chemotherapy in patients with ES-SCLC can be cost-beneficial owing to fewer myelosuppressive AEs and lower costs, together with a favorable QoL profile.

No margin for non-adherence: Probabilistic kaplan-meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study).

BACKGROUND: Although adherence to imatinib is critical for attaining treatment responses in chronic myeloid leukemia, there is evidence of varying adherence among patients. Our aim was to model and determine the margin of tolerance, if any, required to ensure treatment responses among patients prescribed imatinib before treatment response is at risk. METHOD: We performed post hoc analyses of the ADAGIO study conducted in Belgium on 169 evaluable patients (Blood 2009). Applying Kaplan-Meier methods using adherence instead of the conventional time variable, we modeled the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) response as a function of 90-day pill count adherence. RESULTS: Analyses showed that ∼100 % adherence of prescribed dose is associated with probabilities of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR; compared to, 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR) at 90 % adherence. Increasing intake of imatinib from 90 % to 100 % of the prescribed dose increased the likelihood of the various treatment responses by 1.95-2.35-fold. CONCLUSION: There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

Conversion to biosimilar pegfilgrastim-cbqv enables budget-neutral access to FOLFIRINOX treatment for metastatic pancreatic cancer.

Aim: To estimate the cost-savings from conversion to biosimilar pegfilgrastim-cbqv that can be reallocated to provide budget-neutral expanded access to FOLFIRINOX in patients with metastatic pancreatic cancer. Methods: Simulation modeling in a panel of 2500 FOLFIRINOX-treated patients, using varying treatment duration (1-12 cycles) and conversion rates (10-100%), to estimate cost-savings and additional FOLFIRINOX treatment that could be budget neutral. Results: In a 2500-patient panel at 100% conversion, savings of US$6,907.41 per converted patient over 12 cycles of prophylaxis translate to US$17.3 million and could provide 72,273 additional FOLFIRINOX doses or 6023 full 6-month regimens. Conclusion: Conversion to biosimilar CIN/FN prophylaxis can generate significant cost-savings and provide budget-neutral expanded access to FOLFIRINOX treatment for patients with metastatic pancreatic cancer.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. The authors calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 2500 patients with metastatic pancreatic cancer and then computed the number of additional doses of FOLFIRINOX chemotherapy that could be purchased with those savings. Using biosimilar pegfilgrastim for 12 cycles could save US$6,907.41 per patient. If all 2500 patients were treated with biosimilar pegfilgrastim, US$17.3 million could be saved. This could provide 72,273 additional FOLFIRINOX doses. Biosimilar pegfilgrastim can generate significant savings to purchase chemotherapy for additional patients cost-free.

Methods for Conducting Stated Preference Research with Children and Adolescents in Health: A Scoping Review of the Application of Discrete Choice Experiments.

BACKGROUND: Discrete choice experiments (DCEs) are a common method used to describe and quantitatively assess preferences in health applications. Increasingly, DCEs have been used to elicit preferences from children and adolescents and generate evidence to inform policies affecting this population. OBJECTIVES: The aim of this review was to summarize and describe the application of DCEs conducted with children and adolescents and describe author-reported age-specific considerations in design, implementation, and analysis. METHODS: A scoping review was conducted using a 'pearl-growing' technique whereby the reference lists of existing systematic reviews of DCEs were used to identify potential studies conducted with children or adolescents as respondents published between 1990 and 2017. This list was supplemented with an updated electronic search using the same strategy as the initial reviews to identify studies from 2017 to 2020. RESULTS: Of 480 studies identified, 19 were included; topics included vaccines (32%), drugs/medical devices (26%), treatment or health promotion interventions/programs (21%), warning labels on cigarettes/nicotine products (10%), and preferences for physical activity and healthy food choices (10%). The youngest reported age for independent DCE completion was 8 years. Approaches to assessing validity and reliability of choices were consistent with best practices for the conduct of DCEs. Reported age-specific considerations included use of visual aids, age-appropriate language, reducing task complexity and cognitive burden, and exploration of interpretation of willingness-to-pay. CONCLUSION: The number of DCEs conducted with children and adolescents has increased in recent years. Detailed explanation of why reported age-specific considerations were necessary, how they could be used to interpret results, or to understand the appropriateness of this methodology for different age groups was limited. Despite a recognition of the need for special consideration when conducting DCEs in this population, the unique issues in the context of age-specific considerations are largely unexplored, and further research is required. Moving forward, stated preference research conducted with children and adolescents should report in more detail methods of recruitment, results of validity assessments, and provide specific reflection on the extent to which modeled results are consistent with expectations and underlying theory.

Conversion to supportive care with biosimilar pegfilgrastim-cbqv enables budget-neutral expanded access to R-CHOP treatment in non-Hodgkin lymphoma.

This pharmacoeconomic simulation (1) assessed the cost-efficiency of converting a panel of 20,000 patients at risk of chemotherapy-induced (febrile) neutropenia (CIN/FN) from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv; (2) estimated how savings can be used to provide budget-neutral expanded access to R-CHOP therapy for non-Hodgkin lymphoma patients; and 3) determined the number-needed-to-convert (NNC) to purchase one additional dose of R-CHOP (US payer perspective). Model inputs included biosimilar conversion from pre-filled syringe [PFS] or on-body injector [OBI] reference pegfilgrastim; age-proportional blended costs for reference pegfilgrastim PFS and OBI, pegfilgrastim-cbqv and R-CHOP; medication administration costs; biosimilar conversion rates of 10-100 %; and 1-6 cycles of prophylaxis. Cost-savings were used to estimate the number of doses of R-CHOP that could be purchased and the NNC to purchase one additional dose. Converting a panel of 20,000 patients requiring CIN/FN prophylaxis to biosimilar pegfilgrastim-cbqv from a low of 1 cycle and 10 % conversion to a high of 6 cycles and 100 % conversion yielded savings from $1,567,195 to $96,668,126. The budget-neutral acquisition of R-CHOP doses afforded by these savings ranged from 227 to 13,999 doses, the latter enabling 2333 patients to receive 6 cycles of R-CHOP treatment with no additional cost to the payer. These results are achieved if all 20,000 panel patients requiring GCSF support are prophylacted with biosimilar pegfilgrastim-cbqv for 6 cycles, yielding an NNC of 1.43 patients per additional R-CHOP dose. This simulation underscores the clinic-economic benefit of prophylaxis with biosimilar growth factor and pegfilgrastim-cbqv specifically.