Economic evaluations of clinical pharmacy services in Ireland, 2007-2015

Introduction The concept of this thesis was driven by stagnation within the Irish healthcare system. Multiple reports from pharmacy organisations had outlined possible future directions for the profession but progress was minimal, especially in comparison with other countries. The author’s directive was to evaluate the economic impact of a series of clinical pharmacy services (CPS) in hospital and community settings. Methods A systematic review of economic evaluations of clinical pharmacy services in hospital patients was undertaken to gain insight into recent research in the field. Eligible studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), to establish the quality, consistency and transparency of relevant research. A retrospective analysis of an internal hospital pharmacy interventions database was conducted. A method first described by Nesbit et al. was implemented to estimate the level of cost avoidance achieved. A cost-effectiveness analysis based on data from a randomised controlled trial of a pharmacist-supervised patient self-testing (PST) of warfarin therapy is presented. Outcome measure was the incremental cost associated with six months of intervention management. A similar cost-effectiveness analysis based on previously published RCT data was used to evaluate a novel structured pharmacist review of medication in older hospitalised patients. Cost-effectiveness analysis was presented in the form of an incremental cost-effectiveness ratio (ICER). An ICER is an additional cost per unit effect, in the case of this study, the cost of preventing an additional non-trivial ADR in hospital. A method described by Preaud et al. was adapted to estimate the clinical and economic benefit gained from vaccination of patients by a community pharmacist in Ireland in 2013/14. Sample demographic data was obtained from a national chain of community pharmacies and applied to overall national vaccination data. Results Systematic review identified twenty studies which were eligible for inclusion. Overall, pharmacist interventions had a positive impact on hospital budgets. Only three studies (15%) were deemed to be “good-quality” studies. No ‘novel’ clinical pharmacist intervention was identified during the course of this review. Analysis of internal hospital database identified 4,257 interventions documented on 2,147 individual patients over a 12 month period. Substantial cost avoidance of €710,000 was generated over a 1 year period from the perspective of the health care provider. Mean cost avoidance of €166 per intervention was generated. The cost of providing these interventions was €82,000. Substantial net cost-benefits of €626,279 and a cost-benefit ratio of 8.64 : 1 were generated based on this evaluation of pharmacist interventions. Results from an evaluation of a novel pharmacist-led form of warfarin management indicated indicated that on a per patient basis, PST was slightly more expensive than established anticoagulant management. On a per patient basis over a six month period, PST resulted in an incremental cost of €59.08 in comparison with routine care. Overall cost of managing a patient through pharmacist-supervised PST for a six month period is €226.45. However, for this increase in cost a clinically significant improvement in care was provided. Patients achieved a significantly higher time in therapeutic range during the PST arm in comparison with routine care, (72 ± 19.7% vs 59 ± 13.5%). Difference in overall cost was minimal and PST was the dominant strategy in some scenarios examined during sensitivity analysis. Structured pharmacist review of medication was determined to be dominant in comparison to usual pharmaceutical care. Even if the healthcare payer was unwilling to pay any money for the prevention of an ADR, the intervention strategy is still likely to be cost-effective (probability of being determined cost-effective = 0.707). Implementation of pharmacist-led influenza vaccination has resulted in substantial clinical and economic benefits to the healthcare system. The majority of patients (64.9%) who availed of this service had identifiable influenza-related risk factors. Of patients with influenza-related risk factors, age ≥65 year was the most commonly cited risk factor. Pharmacist vaccination services averted a total of 848 influenza cases across all age groups during the 2013/2014 influenza season. Due to receipt of vaccination in a pharmacy setting, 444 influenza-related GP visits were prevented. In terms of more serious influenza-associated events, 11 hospitalisations and five influenza-related deaths were averted. Costs averted were approximately €305,000. These were principally wider societal-related costs associated with lost productivity. Conclusion Overall, clinical pharmacy services are adding value to the Irish healthcare system in both hospital and community settings, but provision of additional funding for new services would enable them to offer a great deal more.

The effects of copayment policies on adherence to prescription medicines in publicly insured populations

Introduction: Copayments for prescriptions are associated with decreased adherence to medicines resulting in increased health service utilisation, morbidity and mortality. In October 2010 a 50c copayment per prescription item was introduced on the General Medical Services (GMS) scheme in Ireland, the national public health insurance programme for low-income and older people. The copayment was increased to €1.50 per prescription item in January 2013. To date, the impact of these copayments on adherence to prescription medicines on the GMS scheme has not been assessed. Given that the GMS population comprises more than 40% of the Irish population, this presents an important public health problem. The aim of this thesis was to assess the impact of two prescription copayments, 50c and €1.50, on adherence to medicines.Methods: In Chapter 2 the published literature was systematically reviewed with meta-analysis to a) develop evidence on cost-sharing for prescriptions and adherence to medicines and b) develop evidence for an alternative policy option; removal of copayments. The core research question of this thesis was addressed by a large before and after longitudinal study, with comparator group, using the national pharmacy claims database. New users of essential and less-essential medicines were included in the study with sample sizes ranging from 7,007 to 136,111 individuals in different medication groups. Segmented regression was used with generalised estimating equations to allow for correlations between repeated monthly measurements of adherence. A qualitative study involving 24 individuals was conducted to assess patient attitudes towards the 50c copayment policy. The qualitative and quantitative findings were integrated in the discussion chapter of the thesis. The vast majority of the literature on this topic area is generated in North America, therefore a test of generalisability was carried out in Chapter 5 by comparing the impact of two similar copayment interventions on adherence, one in the U.S. and one in Ireland. The method used to measure adherence in Chapters 3 and 5 was validated in Chapter 6. Results: The systematic review with meta-analysis demonstrated an 11% (95% CI 1.09 to 1.14) increased odds of non-adherence when publicly insured populations were exposed to copayments. The second systematic review found moderate but variable improvements in adherence after removal/reduction of copayments in a general population. The core paper of this thesis found that both the 50c and €1.50 copayments on the GMS scheme were associated with larger reductions in adherence to less-essential medicines than essential medicines directly after the implementation of policies. An important exception to this pattern was observed; adherence to anti-depressant medications declined by a larger extent than adherence to other essential medicines after both copayments. The cross country comparison indicated that North American evidence on cost-sharing for prescriptions is not automatically generalisable to the Irish setting. Irish patients had greater immediate decreases of -5.3% (95% CI -6.9 to -3.7) and -2.8% (95% CI -4.9 to -0.7) in adherence to anti-hypertensives and anti-hyperlipidaemic medicines, respectively, directly after the policy changes, relative to their U.S. counterparts. In the long term, however, the U.S. and Irish populations had similar behaviours. The concordance study highlighted the possibility of a measurement bias occurring for the measurement of adherence to non-steroidal anti-inflammatory drugs in Chapter 3. Conclusions: This thesis has presented two reviews of international cost-sharing policies, an assessment of the generalisability of international evidence and both qualitative and quantitative examinations of cost-sharing policies for prescription medicines on the GMS scheme in Ireland. It was found that the introduction of a 50c copayment and its subsequent increase to €1.50 on the GMS scheme had a larger impact on adherence to less-essential medicines relative to essential medicines, with the exception of anti-depressant medications. This is in line with policy objectives to reduce moral hazard and is therefore demonstrative of the value of such policies. There are however some caveats. The copayment now stands at €2.50 per prescription item. The impact of this increase in copayment has yet to be assessed which is an obvious point for future research. Careful monitoring for adverse effects in socio-economically disadvantaged groups within the GMS population is also warranted. International evidence can be applied to the Irish setting to aid in future decision making in this area, but not without placing it in the local context first. Patients accepted the introduction of the 50c charge, however did voice concerns over a rising price. The challenge for policymakers is to find the ‘optimal copayment’ – whereby moral hazard is decreased, but access to essential chronic disease medicines that provide advantages at the population level is not deterred. This evidence presented in this thesis will be utilisable for future policy-making in Ireland.

The identification and characterisation of Rab4 interacting proteins

Rab4 is a member of the Rab superfamily of small GTPases. It is localized to the early sorting endosome and plays a role in regulating the transport from this compartment to the recycling and degradative pathways. In order to further our understanding of the role Rab4 plays in endocytosis, a yeast two-hybrid screen was performed to identify putative Rab4 effectors. A constitutively active mutant of Rab4, Rab4Q67L, when used as bait to screen a HeLa cDNA library, identified a novel 80kDa protein that interacted with Rab4-GTP. This protein was called Rab Coupling Protein (RCP). RCP interacts preferentially with the GTP-bound form of Rab4. Subsequent work demonstrated that RCP also interacts with Rab11, and that this interaction is not nucleotide-depenedent. RCP is predominantly membrane-bound and localised to the perinuclear recycling compartment. Expression of a truncation mutant of RCP, that contains the Rab binding domain, in HeLa cells, results in the formation of an extensive tubular network that can be labelled with transferrin. These tubules are derived from the recycling compartment since they are inaccessible to transferrin when the ligand is internalised at 18oC. The truncation mutant-induced morphology can be rescued by overexpression of active Rab11, but not active Rab4. This suggests that RCP functions between Rab4 and Rab11 in the receptor recycling pathway, and may act as a ‘molecular bridge’ between these two sequentially acting small GTPases. Quantitative assays demonstrated that overexpression of the truncation mutant results in a dramatic inhibition in the rate of receptor recycling. Database analysis revealed that RCP belongs to a family of Rab interacting proteins, each characterised by a carboxy-terminal coiled-coil domain and an amino-terminal phospholipid-binding domain. KIAA0941, an RCP homologue, interacts with Rab11, but not with Rab4. Overexpression of its Rab binding domain also results in a tubular network, however, this tubulation cannot be rescued by active Rab11.

Tropospheric aerosol detection over Southern Ireland using a backscatter Raman lidar

Lidar is an optical remote sensing instrument that can measure atmospheric parameters. A Raman lidar instrument (UCLID) was established at University College Cork to contribute to the European lidar network, EARLINET. System performance tests were carried out to ensure strict data quality assurance for submission to the EARLINET database. Procedures include: overlap correction, telecover test, Rayleigh test and zero bin test. Raman backscatter coefficients, extinction coefficients and lidar ratio were measured from April 2010 to May 2011 and February 2012 to June 2012. Statistical analysis of the profiles over these periods provided new information about the typical atmospheric scenarios over Southern Ireland in terms of aerosol load in the lower troposphere, the planetary boundary layer (PBL) height, aerosol optical density (AOD) at 532 nm and lidar ratio values. The arithmetic average of the PBL height was found to be 608 ± 138 m with a median of 615 m, while average AOD at 532 nm for clean marine air masses was 0.119 ± 0.023 and for polluted air masses was 0.170 ± 0.036. The lidar ratio showed a seasonal dependence with lower values found in winter and autumn (20 ± 5 sr) and higher during spring and winter (30 ± 12 sr). Detection of volcanic particles from the eruption of the volcano Eyjafjallajökull in Iceland was measured between 21 April and 7 May 2010. The backscatter coefficient of the ash layer varied between 2.5 Mm-1sr-1 and 3.5 Mm-1sr-1, and estimation of the AOD at 532 nm was found to be between 0.090 and 0.215. Several aerosol loads due to Saharan dust particles were detected in Spring 2011 and 2012. Lidar ratio of the dust layers were determine to be between 45 and 77 sr and AOD at 532 nm during the dust events range between 0.84 to 0.494.

The utility of survey and administrative data to generate information for research and outcomes-based oral health services development

The aim of this research, which focused on the Irish adult population, was to generate information for policymakers by applying statistical analyses and current technologies to oral health administrative and survey databases. Objectives included identifying socio-demographic influences on oral health and utilisation of dental services, comparing epidemiologically-estimated dental treatment need with treatment provided, and investigating the potential of a dental administrative database to provide information on utilisation of services and the volume and types of treatment provided over time. Information was extracted from the claims databases for the Dental Treatment Benefit Scheme (DTBS) for employed adults and the Dental Treatment Services Scheme (DTSS) for less-well-off adults, the National Surveys of Adult Oral Health, and the 2007 Survey of Lifestyle Attitudes and Nutrition in Ireland. Factors associated with utilisation and retention of natural teeth were analysed using count data models and logistic regression. The chi-square test and the student’s t-test were used to compare epidemiologically-estimated need in a representative sample of adults with treatment provided. Differences were found in dental care utilisation and tooth retention by Socio-Economic Status. An analysis of the five-year utilisation behaviour of a 2003 cohort of DTBS dental attendees revealed that age and being female were positively associated with visiting annually and number of treatments. Number of adults using the DTBS increased, and mean number of treatments per patient decreased, between 1997 and 2008. As a percentage of overall treatments, restorations, dentures, and extractions decreased, while prophylaxis increased. Differences were found between epidemiologically-estimated treatment need and treatment provided for those using the DTBS and DTSS. This research confirms the utility of survey and administrative data to generate knowledge for policymakers. Public administrative databases have not been designed for research purposes, but they have the potential to provide a wealth of knowledge on treatments provided and utilisation patterns.