Planned change in modern hierarchical organizations: A three-step model.

Change is often uncomfortable and it is challenging when the need for substantive change emerges in a hierarchical organization. It is critical to consider both processes and people when planned change becomes necessary. Members of the organization may look to existing theories and models that would be helpful to navigate planned change. The authors present the Proposed Model of Planned Change, which is a synthesis of three well-known change theories/models into one cohesive three-step model. This model integrates process, change agent(s), and collaboration with other group members. The authors highlight the model's strengths and limitations in the context of a hierarchical nursing school's curriculum revision as an example. This model could prove useful for similar organizations seeking similar changes, as well as for a variety of organizations in any circumstance where change is desired. The authors will provide a progress report of implementation of this three-step model with lessons learned in a subsequent manuscript.

Quality of life improvement in patients treated with degarelix versus leuprorelin for advanced prostate cancer.

PURPOSE: We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix. MATERIALS AND METHODS: We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12® and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms. Utility was tested for relationships with aspects of the symptom and side effect burden that may be affected by degarelix treatment, that is prostate specific antigen progression and adverse events. RESULTS: Average utility in patients without prostate specific antigen progression or an adverse event was 0.742, similar to previously published utilities for nonprogressed prostate cancer states. Prostate specific antigen progression was associated with a utility decrement of between 0.062 and 0.134 depending on the mapping algorithm used. Of adverse events considered in our analysis musculoskeletal events were associated with the greatest effects on patient utility with a decrement of between 0.029 and 0.086. The 4 mapping algorithms generated similar utility estimates, although values derived from SF-12 were consistently lower than those derived from EORTC QLQ-C30. CONCLUSIONS: Prostate specific antigen progression status and the incidence of treatment and disease related adverse events result in significant decrements to patient health related quality of life. By slowing prostate specific antigen progression degarelix may improve patient utility and the health related quality of life burden.

A cost-utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom.

OBJECTIVE: To determine the cost-effectiveness of the treatment of advanced hormone-dependent prostate cancer with degarelix compared to luteinizing hormone-releasing hormone (LHRH) agonists in the UK using the latest available evidence and the model submitted to AWMSG. METHODS: A cost-effectiveness model was developed from the perspective of the UK National Health Service evaluating monthly injection of degarelix against 3-monthly leuprorelin therapy plus anti-androgen flare cover for the first-line treatment of patients with advanced (locally advanced or metastatic) hormone-dependent prostate cancer. A Markov process model was constructed using the patient population characteristics and efficacy information from the CS21 Phase III clinical trial and associated extension study (CS21A). The intention-to-treat (ITT) population and a high-risk sub-group with a PSA level >20 ng/mL were modeled. RESULTS: In the base-case analysis using the patient access scheme (PAS) price, degarelix was dominant compared to leuprorelin with cost savings of £3633 in the ITT population and £4310 in the PSA > 20 ng/mL sub-group. The chance of being cost-effective was 95% in the ITT population and 96% in the PSA > 20 ng/mL sub-group at a threshold of £20,000 per quality-adjusted life-year (QALY). In addition, degarelix remained dominant when PSA progression was assumed equal and only the benefits of preventing testosterone flare were taken into account. Treatment with degarelix also remained dominant in both populations when the list price was used. The additional investment required to treat patients with degarelix could be offset in 19 months for the ITT population and 13 months for the PSA > 20 ng/mL population. The model was most sensitive to the hazard ratio assumed for PSA progression between degarelix and leuprorelin and the quality-of-life (utility) of patients receiving palliative care. CONCLUSION: Degarelix is likely to be cost-effective compared to leuprorelin plus anti-androgen flare cover in the first-line treatment of advanced hormone-dependent prostate cancer.

Cost and quality-adjusted life year differences in the treatment of active ulcerative colitis using once-daily 4 g or twice-daily 2g mesalazine dosing.

BACKGROUND: Improved compliance in active ulcerative colitis (UC) is likely to improve healthcare efficiency by reducing time spent in active mild to moderate UC state. To establish whether once daily (OD) mesalazine offers economic advantages over twice daily (BD) dosing in active UC, we evaluated the outcomes and costs of a recently published randomized study. METHODS: A cost-effectiveness model with four week Markov cycles was developed to reflect current treatment practices in the Netherlands with OD and BD mesalazine for active UC. The health service perspective of the Netherlands was reflected in the model and considered a 32week time horizon with 4 weekly Markov cycles. Outcomes evaluated in the model were time spent in active and remission UC and the corresponding health-related quality of life associated with different clinical states. This was then used to derive quality adjusted life-years (QALYs) at each treatment stage. RESULTS: A greater proportion of subjects on 4 g OD achieved remission at weeks 4 and 8 compared with 2g BD. After 32 weeks the average costs per patient with active UC were €3097 and €3548 for those treated with OD and BD mesalazine respectively, with an average saving of €451 per patient treated with OD mesalazine. The average costs per QALY for OD and BD mesalazine were €5433 and €6324 for OD and BD, respectively. CONCLUSIONS: Based on the results from a single randomized study, OD dosing resulted in a shorter time spent in active UC which resulted in lower healthcare costs.

Review of the economic evaluations of hormonal therapy for patients with locally advanced prostate cancer.

Androgen deprivation therapy (ADT) is used as first-line therapy for locally advanced or metastatic prostate cancer aiming to reduce testosterone to castrate levels. The authors present an overview of the existing cost-effectiveness studies of ADT in prostate cancer. Cost-effectiveness of ADT was reviewed using a systematic search of the peer-reviewed literature, as well as research abstracts presented at various scientific and industry meetings. Most cost-effectiveness analyses of ADT reported results within the accepted societal threshold of US$50,000 cost/quality-adjusted life year needed to adopt new technology.

Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

A comparison of physician-rated disease severity and patient reported outcomes in mild to moderately active ulcerative colitis.

BACKGROUND AND AIMS: The aim was to derive health state utility scores in ulcerative colitis (UC) by establishing the relationship between the physician-rated ulcerative colitis disease activity index (UCDAI) and a patient reported EQ-5D by statistically mapping the two instruments. METHODS: In a randomised controlled trial comparing oral plus enema mesalazine treatment with oral mesalazine treatment alone (PINCE), UCDAI and EQ-5D scores were collected in parallel from patients with active UC. From these data, multinomial logistic regression was used to estimate response probabilities to each of the five domains of the EQ-5D index from assessment of UC disease severity using original and abbreviated (no endoscopy) versions of the UCDAI. Predicted EQ-5D responses were converted by Monte Carlo simulation to the EQ-5D index for predicting health-related quality of life (HRQoL). The reliability of the algorithm was tested using UCDAI scores from a second mesalazine RCT (PODIUM). RESULTS: The abbreviated-UCDAI showed comparable explanatory performance to the full UCDAI. For patients in remission, mean utility was 0.939, 0.944, and 0.940U for PINCE(estimated), PINCE(observed), and PODIUM, respectively. Mild/moderate and relapsing cases showed mean utilities of 0.801, 0.811, and 0.775, respectively; whilst for those in severe relapse, the mean utilities were 0.630, 0.700 and 0.660 units, respectively. The mean squared error between actual and predicted utilities from observations in PINCE was 0.019. CONCLUSION: Response mapping of UC activity to EQ-5D domains produced reliable estimates of patient-rated health state utility consistent with UCDAI rated severity. Comparing abbreviated-UCDAI and full UCDAI suggests that inclusion of endoscopy scores has limited predictive value in estimating patient HRQoL.

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; P<0.005). The mean costs per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; P<0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (P<0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis.

An economic evaluation comparing once daily with twice daily mesalazine for maintaining remission based on results from a randomised controlled clinical trial.

BACKGROUND AND AIMS: Standard practice to maintain remission in ulcerative colitis (UC) consists of daily mesalazine therapy. However, frequent dosing is associated with poor adherence and increased failure rates. The PODIUM (Pentasa™ Once Daily In UC Maintenance) randomised control trial showed 2 g once daily (OD) to be superior to twice daily (BD) dosing for maintaining remission. We sought to determine whether this alternative dosing regimen is cost-effective. METHODS: An economic evaluation was conducted to compare costs and outcomes of OD with twice daily (BD) dosing. The main outcome considered was quality-adjusted life years (QALYs) based on health state utilities derived from the primary outcome measure, remission without relapse at 12 months defined by a UCDAI score ≤1. The economic evaluation consisted of two health states: (1) remission and (2) active UC. RESULTS: Annual average treatment costs for OD and BD dosing were £654 (95% CI: £536-£759) and £747 (£620-£860), respectively with an average per person savings of £93 per year. Average annual costs of ancillary care for relapse for OD and BD dosing were £307 (£241-£383) and £396 (£320-£483), respectively. Treatment with OD 2 g mesalazine resulted in an incremental QALY improvement of 0.004 units, indicating that it was the dominant treatment option (i.e. improved outcomes and cost-saving). Variations in parameter estimates in the sensitivity analysis indicated that mesalazine had >0.95 probability of being cost-effective compared to BD based on accepted willingness to pay thresholds applied by the UK National Health Service. CONCLUSIONS: Once daily 2 g mesalazine for maintaining remission in UC is cost-saving compared with 1 g twice daily. Cost-savings with 2 g once daily were achieved by differences in ancillary care attributed to higher failure rates observed with 1 g twice daily.

An economic evaluation comparing concomitant oral and topical mesalazine versus oral mesalazine alone in mild-to-moderately active ulcerative colitis based on results from randomised controlled trial.

INTRODUCTION: A previous randomised controlled trial has demonstrated that oral plus topical mesalazine enema is more effective than oral mesalazine alone for achieving clinical remission in mild-to-moderately active extensive ulcerative colitis (UC). To evaluate whether this strategy is cost-effective we conducted an economic evaluation comparing 1 g topical mesalazine in combination with 4 g oral mesalazine compared to 4 g mesalazine monotherapy in mild-to-moderately active UC. METHODS: The economic evaluation was based on the ability to achieve remission using changes from baseline in the ulcerative colitis disease activity instrument (UCDAI). A cost-utility analysis was used where the main outcome was quality-adjusted life years to reflect improved quality of life associated with achieving remission compared with active disease. A simulated Markov model with five health states was constructed to model cost and outcome changes over time: (1) active UC; (2) mesalazine-refractory active UC; (3) steroid-refractory active UC; (4) infliximab-responsive active UC; and (5) remission. To reflect parameter uncertainty in the cost-effectiveness analysis probabilistic sensitivity analysis (PSA) was conducted by varying relevant clinical parameters. RESULTS: Average treatment costs required to transition a patient from active UC to remission using oral and topical mesalazine compared with oral alone were £1812 and £2390, respectively. Improved remission rates attributed to oral and topical mesalazine resulted in moderate improvements in quality-adjusted life years (QALYs) compared to oral mesalazine alone. Disaggregation of medical costs indicated that medical consultations and diagnostic costs were similar for both treatment arms. An abbreviated analysis which considered costs up to steroid-refractory patients in subacute UC indicated that combination therapy offered a cost-savings of £285 over 16 weeks of therapy compared with monotherapy. CONCLUSIONS: The results indicate that the addition of 1 g topical mesalazine results in significant cost-savings and moderate quality of life improvements. We have also shown that irrespective of which treatment modality is used in steroid-refractory patients (eg, infliximab, azathioprine, ciclosporine) that topical mesalazine is cost-saving.

Antibiotic sales and the prevalence of symptoms of asthma, rhinitis, and eczema: The International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: It has been hypothesized that antibiotic use early in life may increase the subsequent risk of asthma. We have conducted an ecologic analysis of the relationship between antibiotics sales and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema in 99 centres from 28 countries. METHODS: Data for antibiotics sales for 28 countries were obtained from the Institute for Medical Statistics (IMS), Health Global Services, UK and converted to defined daily doses (DDD). Data on the prevalence of symptoms of asthma, rhinitis, and eczema in 13-14 year olds were based on the responses to the written and video questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product (GNP) as an estimate of the level of affluence. RESULTS: In general, there was a positive association between per capita antibiotics sales and the prevalence of symptoms for asthma, rhinitis, and eczema, but the associations generally became negative once the analyses had been adjusted for GNP. In particular, there were non-significant negative associations between total antibiotics sales and the prevalence of wheeze ever, wheeze in the last 12 months, nose problems with itchy-watery eyes, itchy rash in the last 12 months, and eczema ever. On the other hand there were weak non-significant positive associations for asthma ever, nose problems ever, nose problems in the last 12 months, and itchy rash ever. There was a statistically significant positive association with wheeze at rest as measured by the asthma video questionnaire; however, even this association was weak and would not account for more than a 1% difference in asthma prevalence between countries. CONCLUSIONS: These findings are generally not consistent with the hypothesis that antibiotic use increases the risk of asthma, rhinitis, or eczema. If there is a causal association of antibiotic use with asthma risk, it does not appear to explain the international differences in asthma prevalence.