scholarly journals Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation

2020 ◽  
Vol 24 (2) ◽  
pp. 1-180 ◽  
Author(s):  
Nigel Fleeman ◽  
Rachel Houten ◽  
Adrian Bagust ◽  
Marty Richardson ◽  
Sophie Beale ◽  
...  

Background Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). Objectives We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. Data sources EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. Review methods We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. Results Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained. Limitations We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. Conclusions Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. Study registration This study is registered as PROSPERO CRD42017055516. Funding The National Institute for Health Research Health Technology Assessment programme.

2014 ◽  
Vol 2 (21) ◽  
pp. 1-118 ◽  
Author(s):  
Fiona Paton ◽  
Duncan Chambers ◽  
Paul Wilson ◽  
Alison Eastwood ◽  
Dawn Craig ◽  
...  

BackgroundThere has been growing interest in the NHS over recent years in the use of enhanced recovery programmes for elective surgery to deliver productivity gains through reduced length of stay, fewer postoperative complications, reduced readmissions and improved patient outcomes.ObjectivesTo evaluate the clinical effectiveness and cost-effectiveness of enhanced recovery programmes for patients undergoing elective surgery in acute hospital settings. To identify and critically describe key factors associated with successful adoption, implementation and sustainability of enhanced recovery programmes in UK settings. To summarise existing knowledge about patient experience of enhanced recovery programmes in UK settings.Data sourcesEight databases, including Database of Abstracts of Reviews and Effects, International Prospective of Systematic Reviews, NHS Economic Evaluation Database and MEDLINE, were searched from 1990 to March 2013 without language restrictions. Relevant reports and guidelines and reference lists of retrieved articles were scanned to identify additional studies.Review methodsSystematic reviews, randomised controlled trials (RCTs), economic evaluations, and UK NHS cost analysis studies were included if they evaluated the impact of enhanced recovery programmes on any health- and cost-related outcomes. Eligible studies included patients undergoing elective surgery in an acute hospital setting. Implementation case studies and surveys of patient experience in a UK setting were also eligible for inclusion. Quality assessment of systematic reviews, RCTs and economic evaluations was based on existing Centre for Reviews and Dissemination processes. All stages of the review process were performed by one researcher and checked by a second with discrepancies resolved by consensus. The type and range of evidence precluded meta-analysis and we therefore performed a narrative synthesis, differentiating between clinical effectiveness and cost-effectiveness, implementation case studies and evidence on patient experience.ResultsSeventeen systematic reviews of varying quality were included in this report. Twelve additional RCTs were included; all were considered at high risk of bias. Most of the evidence focused on colorectal surgery. Fourteen innovation case studies and 15 implementation case studies undertaken in NHS settings were identified and provide descriptions of factors critical to the success of an enhanced recovery programme. Ten relevant economic evaluations were identified evaluating costs and outcomes over short time horizons. Despite the plethora of studies, robust evidence was sparse. Evidence for colorectal surgery suggests that enhanced recovery programmes may reduce hospital stays by 0.5–3.5 days compared with conventional care. There were no significant differences in reported readmission rates. Other surgical specialties showed greater variation in reported reductions in length of stay reflecting the limited evidence identified.LimitationsFindings relating to other clinical outcomes, cost-effectiveness, implementation and patient experience were hampered by a lack of robust evidence and poor reporting.ConclusionsThere is consistent, albeit limited, evidence that enhanced recovery programmes may reduce length of patient hospital stay without increasing readmission rates. The extent to which managers and clinicians considering implementing enhanced recovery programmes can realise reductions and cost savings will depend on length of stays achieved under their existing care pathway. RCTs comparing an enhanced recovery programme with conventional care continue to be conducted and published. Further single-centre RCTs of this kind are not a priority. Rather, what is needed is improved collection and reporting of how enhanced recovery programmes are implemented, resourced and experienced in NHS settings.FundingThe National Institute for Health Research Health Services and Delivery Research programme.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Arash Safavi ◽  
Aparna Vijayasekaran ◽  
Marlon A. Guerrero

The vast majority of patients with differentiated thyroid cancer (DTC) are treated successfully with surgery and radioactive iodine ablation, yet the treatment ofadvancedcases is frustrating and largely ineffective. Systemic treatment with conventional cytotoxic chemotherapy is basically ineffective in most patients with advanced DTC. However, a better understanding of the genetics and biologic basis of thyroid cancers has generated opportunities for innovative therapeutic modalities, resulting in several clinical trials. We aim to delineate the latest knowledge regarding the biologic characteristics of DTC and to describe the available data related to novel targeted therapies that have demonstrated clinical effectiveness.


2015 ◽  
Vol 5 (1) ◽  
pp. 62-76 ◽  
Author(s):  
Joakim Ramsberg ◽  
Martin Neovius

For many interventions in health care, there is limited information on efficacy, safety and cost-effectiveness even long after they have been implemented. To decide between treatments, the randomized controlled trial (RCT) provides the strongest evidence. This creates a problem because RCTs are very expensive, logistically challenging and generally cumbersome. Observational studies are inexpensive, but create weaker evidence. The pragmatic randomized trial, enriched with routinely collected register or electronic health record  (EHR) data may be a solution to this dilemma since they are much less costly than traditional RCTs but create much stronger evidence than observational studies. Pragmatic randomized trials mean that patients in routine care are randomly allocated to alternative treatments. The outcome of the treatment is then followed up in existing registers with patient data. This means that it is possible to 1) follow patients in the normal care situation - unlike the often artificial situation in the traditional RCT, 2) that the costs are low, even for large studies and 3) that a broad spectrum of outcomes, including both health and economic outcomes, can be collected. Pragmatic randomized trials using register or EHR data in principle lend themselves well to health economic evaluations. We have identified a number of such trials in the literature. Very few, however, include economic outcomes.


1997 ◽  
Vol 8 (4) ◽  
pp. 202-208 ◽  
Author(s):  
Fawziah Marra ◽  
Carlo A Marra ◽  
David M Patrick

OBJECTIVE: To assess the cost effectiveness of azithromycin versus doxycycline therapy for cervicalChlamydia trachomatisinfections in Canada.DESIGN: A predictive decision analytic model using previously published clinical and economic evaluations, expert opinion and costs of medical care in Canada.POPULATION: A hypothetical cohort of 5000 women followed over 10 years.INTERVENTIONS: Two diagnostic strategies were compared, laboratory confirmed diagnosis (LCD) and presumptive diagnosis (PD) ofC trachomatisinfection. Under each strategy, two treatment alternatives were analyzed, a single 1 g dose of azithromycin and a seven-day course of doxycycline as 100 mg twice daily.RESULTS: Despite a fourfold higher acquisition cost, under base case conditions, for both diagnostic strategies, the azithromycin treatment alternative was more cost effective than the doxycycline alternative. For the LCD model, the cost per cure for patients receiving azithromycin was $184.76 compared with $240.59 for patients receiving doxycycline, resulting in an incremental cost of $55.83. For the PD model, the cost per cure for patients treated with azithromycin was $51.48 compared with $51.82, resulting in an incremental cost of $0.34. For the hypothetical cohort of 5000 women, the use of azithromycin translates into a projected annual cost savings of $279,150 and $1,700 for the LCD and PD models, respectively. In one-way sensitivity analyses for the LCD model, no clinically plausible changes in the base case estimates changed the results of the cost effectiveness outcome. In the PD model, clinically plausible changes in the probabilities of doxycycline cure, pelvic inflammatory disease, sequelae and chlamydia infection were found to alter the cost effectiveness outcome.CONCLUSIONS: Based on the results from our model, the azithromycin strategy should be employed for the treatment of laboratory confirmed cases. However, for presumptive cases, azithromycin should be used only if the probabilities ofC trachomatisand pelvic inflammatory disease are more than 19%, doxycycline effectiveness is less than 78%, or the cost of azithromycin is less than $19.00.


2020 ◽  
pp. 019459982096698
Author(s):  
Simran Arjani ◽  
Patrick L. Quinn ◽  
Ravi J. Chokshi

Objective To perform a comparative analysis of postthyroidectomy radioactive iodine ablation dosing with or without the implementation of a diagnostic whole-body scan in patients with well-differentiated thyroid cancer. Study Design Decision analysis model. Setting Hospital or ambulatory center. Methods A decision tree model was created to determine the cost-effectiveness of radioactive iodine ablation dosed with diagnostic whole-body scans versus empiric radioactive iodine ablation in patients with differentiated thyroid cancer undergoing postthyroidectomy ablation. The decision tree was populated with values from the published literature. Costs were represented by 2020 Medicare reimbursement rates (US dollars), and morbidity and survival data were used to calculate quality-adjusted life-years. The incremental cost-effectiveness ratio was the primary outcome. Results Empiric radioactive iodine dosing was the dominant economic strategy, producing 0.94 more quality-adjusted life-years while costing $1250.07 less than management with a diagnostic whole-body scan. Sensitivity analyses upheld these results except in cases involving a large discrepancy in successful ablation rates between the diagnostic and empiric treatment arms. Conclusion For patients with differentiated thyroid cancer requiring postthyroidectomy ablation, it is more cost-effective to administer radioactive iodine empirically.


2015 ◽  
Vol 19 (8) ◽  
pp. 1-134 ◽  
Author(s):  
Linda Long ◽  
Simon Briscoe ◽  
Chris Cooper ◽  
Chris Hyde ◽  
Louise Crathorne

BackgroundLateral elbow tendinopathy (LET) is a common complaint causing characteristic pain in the lateral elbow and upper forearm, and tenderness of the forearm extensor muscles. It is thought to be an overuse injury and can have a major impact on the patient’s social and professional life. The condition is challenging to treat and prone to recurrent episodes. The average duration of a typical episode ranges from 6 to 24 months, with most (89%) reporting recovery by 1 year.ObjectivesThis systematic review aims to summarise the evidence concerning the clinical effectiveness and cost-effectiveness of conservative interventions for LET.Data sourcesA comprehensive search was conducted from database inception to 2012 in a range of databases including MEDLINE, EMBASE and Cochrane Databases.Methods and outcomesWe conducted an overview of systematic reviews to summarise the current evidence concerning the clinical effectiveness and a systematic review for the cost-effectiveness of conservative interventions for LET. We identified additional randomised controlled trials (RCTs) that could contribute further evidence to existing systematic reviews. We searched MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Web of Science, The Cochrane Library and other important databases from inception to January 2013.ResultsA total of 29 systematic reviews published since 2003 matched our inclusion criteria. These were quality appraised using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist; five were considered high quality and evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. A total of 36 RCTs were identified that were not included in a systematic review and 29 RCTs were identified that had only been evaluated in an included systematic review of intermediate/low quality. These were then mapped to existing systematic reviews where further evidence could provide updates. Two economic evaluations were identified.LimitationsThe summary of findings from the review was based only on high-quality evidence (scoring of > 5 AMSTAR). Other limitations were that identified RCTs were not quality appraised and dichotomous outcomes were also not considered. Economic evaluations took effectiveness estimates from trials that had small sample sizes leading to uncertainty surrounding the effect sizes reported. This, in turn, led to uncertainty of the reported cost-effectiveness and, as such, no robust recommendations could be made in this respect.ConclusionsClinical effectiveness evidence from the high-quality systematic reviews identified in this overview continues to suggest uncertainty as to the effectiveness of many conservative interventions for the treatment of LET. Although new RCT evidence has been identified with either placebo or active controls, there is uncertainty as to the size of effects reported within them because of the small sample size. Conclusions regarding cost-effectiveness are also unclear. We consider that, although updated or new systematic reviews may also be of value, the primary focus of future work should be on conducting large-scale, good-quality clinical trials using a core set of outcome measures (for defined time points) and appropriate follow-up. Subgroup analysis of existing RCT data may be beneficial to ascertain whether or not certain patient groups are more likely to respond to treatments.Study registrationThis study is registered as PROSPERO CRD42013003593.FundingThe National Institute for Health Research Health Technology Assessment programme.


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