A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial

BackgroundHeavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited.ObjectivesTo assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women’s perspectives on treatment.DesignA pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study.SettingWomen who presented in primary care.ParticipantsA total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment.InterventionsLNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment.Outcome measuresThe primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost–utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses.ResultsThe MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points;p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI –0.6 to 8.3 points;p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women’s experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments.ConclusionsThe LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women’s assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause.Trial registrationCurrent Controlled Trials ISRCTN86566246.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information

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Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Health Technology Assessment ◽

10.3310/hta20440 ◽

2016 ◽

Vol 20 (44) ◽

pp. 1-320 ◽

Cited By ~ 25

Author(s):

John G Williams ◽

M Fasihul Alam ◽

Laith Alrubaiy ◽

Clare Clement ◽

David Cohen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Adverse Reactions ◽

Randomised Trial ◽

Clinical Effectiveness ◽

Health Technology ◽

Mean Difference ◽

Serious Adverse Events ◽

Steroid Resistant ◽

Significant Difference

BackgroundThe efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.MethodBetween May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.ResultsThe 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682;p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096;p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353;p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493;p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;p = 0.998); deaths (all three who died received infliximab;p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773;p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.ConclusionsTotal cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.Trial registrationCurrent Controlled Trials ISRCTN22663589.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.

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Clinical effectiveness and cost-effectiveness of collaborative care for depression in UK primary care (CADET): a cluster randomised controlled trial

Health Technology Assessment ◽

10.3310/hta20140 ◽

2016 ◽

Vol 20 (14) ◽

pp. 1-192 ◽

Cited By ~ 21

Author(s):

David A Richards ◽

Peter Bower ◽

Carolyn Chew-Graham ◽

Linda Gask ◽

Karina Lovell ◽

...

Keyword(s):

Primary Care ◽

Cost Effectiveness ◽

Usual Care ◽

Collaborative Care ◽

Service Use ◽

Controlled Trial ◽

Clinical Effectiveness ◽

Cluster Randomised Controlled Trial ◽

Randomised Controlled

BackgroundCollaborative care is effective for depression management in the USA. There is little UK evidence on its clinical effectiveness and cost-effectiveness.ObjectiveTo determine the clinical effectiveness and cost-effectiveness of collaborative care compared with usual care in the management of patients with moderate to severe depression.DesignCluster randomised controlled trial.SettingUK primary care practices (n = 51) in three UK primary care districts.ParticipantsA total of 581 adults aged ≥ 18 years in general practice with a currentInternational Classification of Diseases, Tenth Edition depressive episode, excluding acutely suicidal people, those with psychosis, bipolar disorder or low mood associated with bereavement, those whose primary presentation was substance abuse and those receiving psychological treatment.InterventionsCollaborative care: 14 weeks of 6–12 telephone contacts by care managers; mental health specialist supervision, including depression education, medication management, behavioural activation, relapse prevention and primary care liaison. Usual care was general practitioner standard practice.Main outcome measuresBlinded researchers collected depression [Patient Health Questionnaire-9 (PHQ-9)], anxiety (General Anxiety Disorder-7) and quality of life (European Quality of Life-5 Dimensions three-level version), Short Form questionnaire-36 items) outcomes at 4, 12 and 36 months, satisfaction (Client Satisfaction Questionnaire-8) outcomes at 4 months and treatment and service use costs at 12 months.ResultsIn total, 276 and 305 participants were randomised to collaborative care and usual care respectively. Collaborative care participants had a mean depression score that was 1.33 PHQ-9 points lower [n = 230; 95% confidence interval (CI) 0.35 to 2.31;p = 0.009] than that of participants in usual care at 4 months and 1.36 PHQ-9 points lower (n = 275; 95% CI 0.07 to 2.64;p = 0.04) at 12 months after adjustment for baseline depression (effect size 0.28, 95% CI 0.01 to 0.52; odds ratio for recovery 1.88, 95% CI 1.28 to 2.75; number needed to treat 6.5). Quality of mental health but not physical health was significantly better for collaborative care at 4 months but not at 12 months. There was no difference for anxiety. Participants receiving collaborative care were significantly more satisfied with treatment. Differences between groups had disappeared at 36 months. Collaborative care had a mean cost of £272.50 per participant with similar health and social care service use between collaborative care and usual care. Collaborative care offered a mean incremental gain of 0.02 (95% CI –0.02 to 0.06) quality-adjusted life-years (QALYs) over 12 months at a mean incremental cost of £270.72 (95% CI –£202.98 to £886.04) and had an estimated mean cost per QALY of £14,248, which is below current UK willingness-to-pay thresholds. Sensitivity analyses including informal care costs indicated that collaborative care is expected to be less costly and more effective. The amount of participant behavioural activation was the only effect mediator.ConclusionsCollaborative care improves depression up to 12 months after initiation of the intervention, is preferred by patients over usual care, offers health gains at a relatively low cost, is cost-effective compared with usual care and is mediated by patient activation. Supervision was by expert clinicians and of short duration and more intensive therapy may have improved outcomes. In addition, one participant requiring inpatient treatment incurred very significant costs and substantially inflated our cost per QALY estimate. Future work should test enhanced intervention content not collaborative care per se.Trial registrationCurrent Controlled Trials ISRCTN32829227.FundingThis project was funded by the Medical Research Council (MRC) (G0701013) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership.

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Laparoscopic supracervical hysterectomy compared with second-generation endometrial ablation for heavy menstrual bleeding: the HEALTH RCT

Health Technology Assessment ◽

10.3310/hta23530 ◽

2019 ◽

Vol 23 (53) ◽

pp. 1-108

Author(s):

Kevin Cooper ◽

Suzanne Breeman ◽

Neil W Scott ◽

Graham Scotland ◽

Rodolfo Hernández ◽

...

Keyword(s):

Cost Effectiveness ◽

Second Generation ◽

Clinical Effectiveness ◽

Health Technology ◽

Endometrial Ablation ◽

Total Hysterectomy ◽

Significant Difference ◽

Post Randomisation

Background Heavy menstrual bleeding (HMB) is a common problem that affects many British women. When initial medical treatment is unsuccessful, the National Institute for Health and Care Excellence recommends surgical options such as endometrial ablation (EA) or hysterectomy. Although clinically and economically more effective than EA, total hysterectomy necessitates a longer hospital stay and is associated with slower recovery and a higher risk of complications. Improvements in endoscopic equipment and training have made laparoscopic supracervical hysterectomy (LASH) accessible to most gynaecologists. This operation could preserve the advantages of total hysterectomy and reduce the risk of complications. Objectives To compare the clinical effectiveness and cost-effectiveness of LASH with second-generation EA in women with HMB. Design A parallel-group, multicentre, randomised controlled trial. Allocation was by remote web-based randomisation (1 : 1 ratio). Surgeons and participants were not blinded to the allocated procedure. Setting Thirty-one UK secondary and tertiary hospitals. Participants Women aged < 50 years with HMB. Exclusion criteria included plans to conceive; endometrial atypia; abnormal cytology; uterine cavity size > 11 cm; any fibroids > 3 cm; contraindications to laparoscopic surgery; previous EA; and inability to give informed consent or complete trial paperwork. Interventions LASH compared with second-generation EA. Main outcome measures Co-primary clinical outcome measures were (1) patient satisfaction and (2) Menorrhagia Multi-Attribute Quality-of-Life Scale (MMAS) score at 15 months post randomisation. The primary economic outcome was incremental cost (NHS perspective) per quality-adjusted life-year (QALY) gained. Results A total of 330 participants were randomised to each group (total n = 660). Women randomised to LASH were more likely to be satisfied with their treatment than those randomised to EA (97.1% vs. 87.1%) [adjusted difference in proportions 0.10, 95% confidence interval (CI) 0.05 to 0.15; adjusted odds ratio (OR) from ordinal logistic regression (OLR) 2.53, 95% CI 1.83 to 3.48; p < 0.001]. Women randomised to LASH were also more likely to have the best possible MMAS score of 100 (68.7% vs. 54.5%) (adjusted difference in proportions 0.13, 95% CI 0.04 to 0.23; adjusted OR from OLR 1.87, 95% CI 1.31 to 2.67; p = 0.001). Serious adverse event rates were low and similar in both groups (4.5% vs. 3.6%). There was a significant difference in adjusted mean costs between LASH (£2886) and EA (£1282) at 15 months, but no significant difference in QALYs. Based on an extrapolation of expected differences in cost and QALYs out to 10 years, LASH cost an additional £1362 for an average QALY gain of 0.11, equating to an incremental cost-effectiveness ratio of £12,314 per QALY. Probabilities of cost-effectiveness were 53%, 71% and 80% at cost-effectiveness thresholds of £13,000, £20,000 and £30,000 per QALY gained, respectively. Limitations Follow-up data beyond 15 months post randomisation are not available to inform cost-effectiveness. Conclusion LASH is superior to EA in terms of clinical effectiveness. EA is less costly in the short term, but expected higher retreatment rates mean that LASH could be considered cost-effective by 10 years post procedure. Future work Retreatment rates, satisfaction and quality-of-life scores at 10-year follow-up will help to inform long-term cost-effectiveness. TriaI registration Current Controlled Trials ISRCTN49013893. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 53. See the NIHR Journals Library website for further project information.

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Clinical effectiveness of health visitor training in psychologically informed approaches for depression in postnatal women: pragmatic cluster randomised trial in primary care

BMJ ◽

10.1136/bmj.a3045 ◽

2009 ◽

Vol 338 (jan15 2) ◽

pp. a3045-a3045 ◽

Cited By ~ 116

Author(s):

C J. Morrell ◽

P. Slade ◽

R. Warner ◽

G. Paley ◽

S. Dixon ◽

...

Keyword(s):

Primary Care ◽

Randomised Trial ◽

Clinical Effectiveness ◽

Health Visitor ◽

Cluster Randomised Trial ◽

Cluster Randomised ◽

Postnatal Women

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ImmunoCAP® ISAC and Microtest for multiplex allergen testing in people with difficult to manage allergic disease: a systematic review and cost analysis

Health Technology Assessment ◽

10.3310/hta20670 ◽

2016 ◽

Vol 20 (67) ◽

pp. 1-178 ◽

Cited By ~ 13

Author(s):

Marie Westwood ◽

Bram Ramaekers ◽

Shona Lang ◽

Nigel Armstrong ◽

Caro Noake ◽

...

Keyword(s):

Quality Of Life ◽

Cost Effectiveness ◽

Conference Proceedings ◽

Citation Index ◽

Clinical Effectiveness ◽

Short Term ◽

Cost Analyses ◽

Immunocap Isac

BackgroundAllergy is a form of immune-mediated exaggerated sensitivity (hypersensitivity) to a substance that is either inhaled, swallowed, injected or comes into contact with the skin. Foreign substances that provoke allergies are called allergens. It has been claimed that multiplex allergen testing may help in diagnosing the cause of symptoms in patients with an unclear cause of allergy or who are allergic to more than one substance.ObjectivesTo evaluate multiplex allergen testing [devices that can measure the presence of multiple immunoglobulin E (IgE) antibodies in a patient’s blood at the same time], by assessing (1) clinical effectiveness (allergy symptoms, incidence of acute exacerbations, mortality, adverse events of testing and treatment, health-care presentations or admissions, health-related quality of life); (2) effects on treatment (diet, immunotherapy medications, other potential testing); (3) any additional diagnostic information provided by multiplex allergen testing; and (4) cost-effectiveness (cost of different assessment strategies).MethodsFifteen databases were searched from 2005 to April 2015, including MEDLINE (via OvidSp), MEDLINE In-Process Citations, MEDLINE Daily Update, PubMed (National Library of Medicine), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Science Citation Index (SCI), Conference Proceedings Citation Index-Science (CPCI-S), BIOSIS Previews, Latin American and Caribbean Health Sciences Literature (LILACS), National Institute for Health Research (NIHR) HTA programme, and the US Food and Drug Administration (FDA); supplementary searches of conference proceedings and trials registries were performed. Review methods followed published guidance from the Cochrane Collaboration and the Centre for Reviews and Dissemination, University of York, UK. The methodological quality of included studies was assessed using appropriate published tools or a review-specific tool designed by the project team. Studies were summarised in a narrative synthesis. Owing to a lack of data on the clinical effectiveness of multiplex allergen testing, no long-term cost-effectiveness model was developed. A conceptual model structure was developed and cost analyses were performed to examine the short-term costs of various possible diagnostic pathways.ResultsFifteen studies were included in the review. The very limited available data indicated that the addition of multiplex allergen testing [ImmunoCAP®Immuno Solid-phase Allergen Chip (ISAC), Thermo Fisher Scientific/Phadia AB, Uppsala, Sweden] to standard diagnostic work-up can change the clinicians’ views on the diagnosis, management and treatment of patients. There was some indication that the use of ImmunoCAP ISAC testing may be useful to guide decisions on the discontinuation of restrictive diets, the content of allergen-specific immunotherapy (SIT) prescriptions, and whether or not patients should receive SIT. However, none of the studies that we identified reported any information on clinical outcomes subsequent to changes in treatment or management. There was some evidence that ImmunoCAP ISAC may be useful for discriminating allergens that are structurally similar and are recognised by the same IgE antibody (cross-immunoreactive). No data were available for Microtest (Microtest Matrices Ltd, London, UK). Detailed cost analyses suggested that multiplex allergen testing would have to result in a substantial reduction of the proportions of patients receiving single IgE testing and oral food challenge tests in order to be cost-saving in the short term.ConclusionsNo recommendations for service provision can be made based on the analyses included in this report. It is suggested that a consensus-based protocol for the use of multiplex allergen testing be developed. The clinical effectiveness and cost-effectiveness of the proposed protocol should then be assessed by comparing long-term clinical and quality of life outcomes and resource use in patients managed using the protocol with those managed using a standard diagnostic pathway.Study registrationThis study is registered as PROSPERO CRD42015019739.FundingThis project was a Diagnostic Assessment Report commissioned by the NIHR HTA programme on behalf of the National Institute for Health and Care Excellence.

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United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care

BMJ ◽

10.1136/bmj.38282.607859.ae ◽

2004 ◽

Vol 329 (7479) ◽

pp. 1381 ◽

Cited By ~ 136

Author(s):

Keyword(s):

Primary Care ◽

United Kingdom ◽

Back Pain ◽

Cost Effectiveness ◽

Randomised Trial ◽

Physical Treatments ◽

Trial Cost

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EVIDENCE REQUIREMENTS FOR REIMBURSEMENT OF PHARMACEUTICALS ACROSS EUROPE

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462315000227 ◽

2015 ◽

Vol 31 (1-2) ◽

pp. 59-67 ◽

Cited By ~ 5

Author(s):

Oyinlola Oyebode ◽

Zoe Garrett ◽

Elizabeth George ◽

Agnese Cangini ◽

Luisa Anna Adele Muscolo ◽

...

Keyword(s):

Cost Effectiveness ◽

Relative Effectiveness ◽

Clinical Effectiveness ◽

Health Technology ◽

Health Condition ◽

Level Of Detail ◽

Specific Information ◽

Target Disease ◽

Guidance Documents ◽

Effectiveness Assessment

Objectives: The objective of this study was to compare evidence requirements for health technology assessment of pharmaceuticals by national agencies across Europe responsible for reimbursement decisions focusing specifically on relative effectiveness assessment.Methods: Evidence requirements from thirty-three European countries were requested and twenty-nine national agencies provided documents to review. Data were extracted from national documents (manufacturer's submission templates and associated guidance) into a purpose-made framework with categories covering information about the health condition, the technology, clinical effectiveness and safety.Results: The level of detail in the required evidence varies considerably across countries. Some countries include specific questions while others request information under general headings. Some countries include all information in a single document, which may or may not include guidance on how to complete the template. Others have specific guidance documents or methods and process manuals that help with the completion of the submission templates. Despite differences in quantity and detail, the content of the evidence requirements is broadly similar. All countries ask for information on the health technology, target disease, and clinical effectiveness and safety. However, one country only requests clinical effectiveness information as part of cost-effectiveness analyses. We found twenty-six evidence requirements for which generic answers may apply across borders and nineteen in which countries requested nationally specific information.Conclusions: This work suggests that it would be possible to put together a minimum set of evidence requirements for HTA to support reimbursement decisions across Europe which could facilitate collaboration between jurisdictions.

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