Initial therapy, persistence and regimen change in a cohort of newly treated type 2 diabetes patients.

AIMS: The aim was to describe the utilization of antidiabetic agents, in terms of persistence and regimen change, in the management of a cohort of newly treated type 2 diabetes patients and to investigate associated socio-demographic and treatment factors. METHODS: A population-based retrospective cohort study was conducted using the national pharmacy claims database in Ireland. Subjects were analyzed for persistence and regimen change. Cox proportional hazards regression examined associations of socio-demographic and treatment factors on treatment patterns. Hazard ratios (HR) and 95% CIs are presented. RESULTS: A total of 20947 subjects were identified in the study over a 2 year period. Most were initiated on metformin (76%) or sulphonylureas (22%) and 77% were persistent with therapy 12 months after initiation. The likelihood of non-persistence was significantly lower in the youngest (40-49 years) age groups (reference 60-69 years) (HR 1.62, 95% CI 1.42, 1.84) and those on sulphonylureas (HR 1.49, 95% CI 1.36, 1.64). The likelihood of receiving a regimen change was significantly lower in the older (80+ years) age groups (HR 0.63, 95% CI 0.56, 0.71), females (HR 0.91, 95% CI 0.86, 0.95), and those with pre-existing CVD (1 vs. 0 CVD medicines) (HR 0.82, 95% CI 0.74, 0.90), and higher in those on sulphonylureas (HR 1.83, 95% CI 1.73, 1.94). CONCLUSIONS: Type of treatment, pre-existing CVD and demographic factors are shown to be associated with the observed treatment patterns. Guideline recommended agents were widely used on treatment initiation though a substantial minority were not initiated on the recommended first line agent. Use of guideline recommended agents was not as evident during treatment progression. Further optimization of initial and subsequent antidiabetic agent prescribing may be possible.

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland.

BACKGROUND: Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. METHODS: A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55-74 years, and (c) biennial faecal immunochemical tests (FIT) at 55-74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55-64 years) and staggered age-based roll-out across the 55-74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55-74). RESULTS: FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381-1,053 with FSIG-based, and 967-1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. CONCLUSIONS: While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning.

Analysis of Health Technology Assessments of Orphan Drugs in Ireland from 2012 to 2017.

BACKGROUND: In Ireland, health technology assessment (HTA) submissions for orphan drugs or drugs for rare diseases have increased in recent years but have not been explicitly analysed. All evaluations are conducted by the National Centre for Pharmacoeconomics (NCPE). OBJECTIVES: The objectives of this study were to ascertain the number of orphan drug submissions to the NCPE and determine how these drugs proceeded through the NCPE critical evaluation process compared with non-orphan drug submissions. METHODS: This was a retrospective analysis of applicant rapid review submissions made to the NCPE from January 2012 to December 2017 inclusive. Drugs were categorised according to the following definitions: orphan (non-cancer) drug, orphan (cancer) drug and ultra-orphan drug. In each of the three categories, the outcome of rapid review appraisal, and where relevant, the outcome of the subsequent HTA was recorded. RESULTS: During the period of study, 280 rapid review submissions were made to the NCPE, of which 21 were for orphan (non-cancer) drugs, 24 were for orphan (cancer) and ten were for ultra-orphan drugs. After rapid review, 44%, 78% and 100% of orphan (non-cancer) drugs, orphan (cancer) drugs and ultra-orphan products, respectively, were recommended for full HTA. When the outcome of the rapid review process was compared between orphan drugs and non-orphan drugs, a statistically significant difference was detected in the proportion of rapid reviews for which the outcome was 'HTA recommended' (Pearson's Chi-squared test; p = 0.04). CONCLUSIONS: The number of submissions to the NCPE for orphan drugs has increased in recent years. The rapid review and HTA process in Ireland plays a role in supporting the reimbursement decision-making process for orphan drugs in a similar manner to the process established for non-orphan drugs. However, the outcome of the reimbursement process for orphan drugs versus non-orphan drugs (in terms of access for patients) has yet to be quantified.

Economic evaluation of a universal childhood pneumococcal conjugate vaccination strategy in Ireland.

OBJECTIVE: To evaluate the cost-effectiveness of implementing a universal infant 7-valent pneumococcal conjugate vaccine (PCV7) vaccination program in the Irish health-care setting from the health-care payers' perspective. METHODS: A model was constructed in MS Excel to follow a cohort of vaccinated and unvaccinated individuals from birth over a 5-year period. The reduction in events that would be associated with PCV7 vaccination and the mortality and cost resulting from these events were analyzed. In a separate submodel, the effect of herd immunity was investigated. RESULTS: Implementing a PCV7 vaccine program in Ireland in a birth cohort of 61,000 infants would be expected to prevent 7703 cases of pneumococcal-related infections over 5 years, resulting in costs avoided of 2.05 million euros increasing to 4.6 million euros if the effect of herd immunity was included. The baseline incremental cost-effectiveness ratio was 249,591 euros/life years gained (LYG), which reduced to 5997 euros/LYG when the effect of herd immunity was included. CONCLUSIONS: A universal infant pneumococcal conjugate vaccination could be considered highly cost-effective in the Irish health-care setting from a health-care payers' perspective, if viewed in terms of the herd immunity effect. The results of this study have positive ramifications for countries in the early stages of health technology assessment.

Economic Evaluation of Selective Neonatal Bacillus Calmette-Guérin Vaccination of High-risk Infants in Ireland.

BACKGROUND: In Western Europe, currently only Ireland and Portugal continue to provide universal neonatal bacillus Calmette-Guérin (BCG) vaccination programs, despite not being considered as high tuberculosis (TB) incidence countries. Other European countries only vaccinate infants considered at high risk of contracting TB. We evaluated the cost-effectiveness of selective BCG vaccination compared with strategies of universal and no vaccination. METHODS: An economic model was used to simulate a cohort from birth to life expectancy, taking the perspective of the publicly funded healthcare system. BCG protection was modeled to last 15 years. International vaccine efficacy data were combined with Irish epidemiologic and cost data. The model took into account long-term sequelae associated with TB meningitis and severe adverse reactions relating to the BCG vaccine. A fully probabilistic model was used to incorporate uncertainty across all parameters. RESULTS: At &OV0556;139,557 per quality-adjusted life year, selective vaccination was not cost-effective relative to a program of no vaccination. The incremental cost-effectiveness of universal vaccination was &OV0556;2.55 million per quality-adjusted life year relative to selective vaccination. There was substantial uncertainty regarding the effectiveness of BCG vaccination. The cost-effectiveness of selective vaccination could be substantially improved by reducing the cost of administering the vaccine. CONCLUSIONS: In the absence of changes to other aspects of TB control, a switch to selective vaccination will result in increased cases of childhood TB. Although not considered cost-effective, selective vaccination may be preferable to no vaccination until other changes to TB control may be implemented to reduce the risk of TB in children.

Evaluating the neonatal BCG vaccination programme in Ireland.

BACKGROUND: The aim of this study was to compare the cost effectiveness of the current Irish programme of universal BCG vaccination of infants versus a programme which considered selectively vaccinating high risk infants using decision analytical modelling. METHODS: The efficacy of the BCG vaccine was re-evaluated to inform a decision analytical model constructed to follow a birth cohort of vaccinated and unvaccinated infants over a 15 year time horizon. The number of life years gained (LYG) was the primary outcome measure and this was compared to the net cost of the vaccination strategies. RESULTS: In the base case analysis, the incremental cost effectiveness ratios (ICERs) for the universal strategy and selective strategy vs no vaccination were €204,373/LYG and €143,233/LYG respectively. When comparing the incremental difference in moving from the universal to the selective strategy, the selective strategy costs €1,055,692 less per 4.8 life years lost per birth cohort. One way sensitivity analyses highlighted that a move from the universal to the selective strategy was particularly sensitive to the estimate of vaccine efficacy against deaths, the cost of administering the vaccine and the multiplier used to apportion risk of contracting tuberculosis. Probabilistic analysis suggested that a move from a universal based strategy to a selective based strategy could be deemed cost effective (probability of cost effectiveness is 76.8 %). CONCLUSION: The results of the study support the protective effect of the BCG vaccine in infants and quantified the cost effectiveness of the current BCG vaccination strategy and the decremental difference in moving to a selective strategy. This analysis highlights that the additional protection offered by the universal vaccination strategy is small compared to that of the selective strategy. Consideration should therefore be given to the implementation of a selective vaccination strategy, and diverting resources to improve TB case management and control.

Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models.

BACKGROUND: Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. METHODS: We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). FINDINGS: 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46-0·68) and 0·36 (0·28-0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90-1·00) and 0·83 (0·75-1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13-0·32) and 0·35 (0·27-0·39) for 40% coverage, and 0·07 (0·00-0·10) and 0·16 (0·01-0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). INTERPRETATION: Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. FUNDING: Canadian Institutes of Health Research.

Cost containment interventions introduced on the community drugs schemes in Ireland-evaluation of expenditure trends using a national prescription claims database.

BACKGROUND: The majority of pharmaceutical expenditure in Ireland occurs in the community for services provided by general practitioners and pharmacists. In the current national and international economic climate, it is anticipated that demand on these services will continue to grow. OBJECTIVE: The aim of this article was to examine trends in expenditure of pharmaceuticals on the Community Drugs Schemes from 2005 to 2010, and to examine the impact of cost-containment interventions on expenditures that were introduced at this time and affected the pricing mechanism for pharmaceuticals in Ireland. METHODS: Prescription data were analyzed using an Irish national prescription claims database according to drug category, that is, generic, patent, and off patent for the 2 largest schemes; the publicly funded General Medical Services (GMS) Scheme and copayment Drugs Payment (DP) Scheme. Segmented regression analysis of interrupted time series was used to analyze the effects of the interventions on expenditure. RESULTS: An increase in expenditure was noted across all schemes up to 2009 and declined thereafter to the end of the study period (October 2010). Significant reductions in expenditure were noted after introduction of a 20% price cut to patent-expired products (off patents) (P < 0.001). In July 2009, pharmacy and wholesale margins were reduced, resulting in significant reductions in expenditure for patented (GMS Scheme: P < 0.05 and DP Scheme: P < 0.001) and generic (DP Scheme only: P < 0.01) products. Significant reductions in expenditure were noted for off-patent products on the GMS Scheme at this time (P < 0.01). No significant reductions in expenditure were noted for off patents after a 15% price reduction in January 2009. An additional 40% price reduction in February 2010 resulted in significant reductions in expenditure for off-patent products on both the GMS (P < 0.01) and DP Scheme (P < 0.05). CONCLUSIONS: Results from this study, based on a section of the total population of Ireland during a 6-year period, indicate that reductions in the wholesale margin and pharmacy markup had the largest impact on reducing pharmaceutical expenditure during the study period.

Public drug expenditure in the Republic of Ireland.

In Ireland, expenditure on medicines in the community has increased over sixfold from 300 million euro in 1998 to 1.9 billion euro in 2008. The Health Service Executive has examined all aspects of the drugs supply chain in an attempt to obtain value for money. The 2006 agreement between the Health Service Executive and the Irish Pharmaceutical Healthcare Association resulted in a 35% reduction in the price of patent-expired medicines with estimated savings of 248 million euro. The agreement has been extended to 2012 providing a further 40% price reduction for those off-patent products. Reductions in wholesaler margins and pharmacy reimbursement will provide savings of 130 million euro per annum. Patient co-payment under the Drugs Payment Scheme increased to 120 euro per month and a new co-payment for medical card holders is to be introduced. Since September 2009, all new pharmaceutical products are considered for pharmacoeconomic assessment. Generic substitution and reference pricing are to be introduced in 2011.

Pharmacoeconomic evaluation in Ireland: a review of the process.

To describe the pharmacoeconomic assessment process in Ireland and to provide examples of recent appraisals and the subsequent impact on pricing and reimbursement decisions. The pharmacoeconomic appraisals conducted by the National Centre for Pharmacoeconomics (NCPE) between September 2006 and February 2009 were reviewed. The NCPE recommendations and subsequent reimbursement decisions by the Health Service Executive (HSE) were recorded. Recommendations made by the NCPE were compared with those of UK agencies. The duration of the NCPE pharmacoeconomic process and the time from marketing authorization to reimbursement was estimated. The budget impact assessments from the pharmaceutical companies were reviewed and compared for consistency. The NCPE conducted 12 single technology appraisals during the study period. Eight of the medicines assessed were either recommended as a cost-effective use of resources or recommended with certain restrictions, and were funded by the HSE. Of the four medicines that were not considered cost effective, two were reimbursed after a price reduction was negotiated and the remaining two were not. The NCPE recommendations concurred with those of the UK agencies for the majority of appraisals, with the exception of sunitinib and lapatinib. The average duration of the NCPE process was 2.7 months. The average time from marketing authorization to reimbursement was 7 months. The review of budget impact assessments highlighted a high degree of variability between submissions. The findings of this review highlight the efficiency of the pharmacoeconomic process and the acceptance of the NCPE recommendations by the HSE for pricing and reimbursement decisions. NCPE recommendations broadly concurred with those of UK agencies for the majority of appraisals.

Cost-effectiveness of human papillomavirus vaccine in reducing the risk of cervical cancer in Ireland due to HPV types 16 and 18 using a transmission dynamic model.

We evaluated the cost-effectiveness of combining a cervical cancer screening programme with a national HPV vaccination programme compared to a screening programme alone to prevent cervical dysplasia and cervical cancer related to HPV types 16 and 18 in the Irish healthcare setting. The incremental cost effectiveness of vaccination strategies for 12-year-old females (base-case) and 12-26-year-old catch-up vaccination strategies were examined. The base-case incremental cost-effectiveness ratio was euro17,383/LYG. Using a probabilistic sensitivity analysis about the base-case, the 95% CI for cost per LYG was (euro3400 to euro38,400). This suggests that vaccination against HPV types 16 and 18 would be cost-effective from the perspective of the Irish healthcare payer.

Characterizing new users of NSAIDs before and after rofecoxib withdrawal.

AIMS: To characterize patients initiated on nonsteroidal anti-inflammatory drugs (NSAIDs), pre and postrofecoxib withdrawal, by age, gender and concomitant cardiovascular (CV) therapy. METHODS: A national primary care prescription database was used to identify patients who initiated NSAID therapy pre and postrofecoxib withdrawal. Patients receiving CV therapy were identified in the same periods also. Adjusted odds ratios (OR) and 95% confidence intervals are presented. RESULTS: Female patients [OR = 1.15 (1.11, 1.19)], those over 65 years [OR = 2.76 (2.65, 2.86)] and those at CV risk [OR = 1.72 (1.67, 1.79)] were more likely to start on celecoxib (over a nonselective NSAID) than male patients, those under 65 years and those not at CV risk. Similar results were found for rofecoxib and nimesulide. Post-withdrawal analysis showed results comparable to the pre-withdrawal period. CONCLUSION: The results highlight a possible uncertainty experienced by prescribers of treatment alternatives available and a lack of unbiased information at this time for at-risk groups.

Regional variation in the prescribing for diabetes and use of secondary preventative therapies in Ireland.

PURPOSE: To compare the prescribing of secondary preventative therapies for patients with both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in the eight health board regions of Ireland. METHODS: We utilized data from the national general medical services (GMS) prescribing database to examine the variability of prescribing for diabetes and associated secondary therapies between regions in those aged 45 years or more. Age-sex standardized prescribing rates of six secondary preventative therapies (aspirin, beta-blockers, statins, ACE inhibitors, angiotensin receptor (AT2) antagonists, and fibrates) were calculated for each region. RESULTS: Variations exist between regions for treated NIDDM (1.5-fold) and IDDM (1.5-fold). Wide variations were observed between regions for prescribing of secondary preventative therapies with the highest variability observed for statin prescribing (1.5- to 1.6-fold) and for AT2 antagonist prescribing (2.0-fold) in NIDDM patients. In those with NIDDM, men were more likely to receive aspirin OR=1.26 (1.21--1.31), ACE inhibitors 1.14 (1.101.18), and fibrates OR=1.55 (1.23--1.96) than women and those aged over 75 years were less likely to receive statins OR=0.60 (0.56--0.65) and fibrates OR=0.25 (0.17--0.37) than those aged 45--74. Similar results were also shown for patients with IDDM. CONCLUSIONS: The results suggest that access to secondary preventative therapy in diabetes patients is not equitable across regions, gender, and age in Ireland. While much of the variability remains unexplained, it may be due to differences in screening and health promotion between regions, prescriber uncertainty, variability in clinical need, or may be derived from a socioeconomic disparity among regions.

Usage of paracetamol-containing combination analgesics remains high in primary care.

AIMS: Paracetamol-containing combination analgesics are widely prescribed but the use of paracetamol/dextropropoxyphene (co-proxamol) is particularly controversial. We aim to examine the prescribing patterns of the paracetamol-containing analgesics in Ireland. METHODS: A national primary care prescribing database was used to investigate patterns of usage. Twenty-six thousand three hundred and eighteen patients who were new to therapy with paracetamol and paracetamol-containing analgesics between January and June 2002 were identified as follows: no previous analgesic medication in the 6 months prior to enrolment into the study, and followed up for at least 12 months from the time of enrolment. Duration of therapy and the number of prescriptions received post enrolment were analyzed according to age. Odds ratios for receiving long-term (>1 month) compared with short-term (1 month) prescriptions for co-proxamol, paracetamol only or a paracetamol combination-type analgesic were calculated for women vs. men, and in those aged over 65 vs. those aged under 65 years. RESULTS: Co-proxamol was the most commonly prescribed analgesic, accounting for 42% of all prescriptions dispensed during 2003. Long-term use of paracetamol-containing analgesic preparations was uncommon, with 56.7% receiving only 1 month's prescription during the study period. However, women (OR = 1.18, 95% CI 1.07, 1.28, P < 0.0001) and those over 65 years (OR = 1.71, 95% CI 1.57, 1.86, P < 0.0001) were more likely to receive a follow-up prescription for co-proxamol, but also for paracetamol (women, OR = 1.28, 95% CI 1.16, 1.39; over 65 year olds, OR = 2.67, 95% CI 2.44, 2.93) and the paracetamol combinations (women, OR = 1.33, 95% CI 1.20, 1.47; over 65 year olds, OR = 1.69, 95% CI 1.53, 1.87). CONCLUSIONS: Co-proxamol was the most commonly prescribed paracetamol-containing analgesic preparation in Ireland. The results may indicate inappropriate use in primary care.