Statement of contribution
F IGURE 4 D OMAINS ON THE COST EFFECTIVENESS PLANE D ASHED LINE INDICATES COST EFFECTIVENESS ACCEPTABILITY THRESHOLD
If the intervention is less effective and more costly (quadrant A) than the comparator, then it is said to be dominated by the comparator. This indicates that the intervention should not be adopted. Conversely, if the intervention is dominant (more effective and less costly than the comparator, falling into quadrant D), then it should be adopted. In both scenarios, there is no need to conduct an economic evaluation. However, should the intervention fall into quadrants B or C, then it may be considered cost-effective if it falls within a threshold of acceptance (sub quadrants C2 and B2). Notably, cost- effectiveness is an arbitrary threshold and may vary according to a multitude of circumstances. In Figure 4, two different thresholds of cost-effectiveness are shown to illustrate this. For both thresholds, the region below the line may be considered cost- effective, and the region above not cost-effective.
There are numerous thresholds of acceptance in use worldwide. The World Health Organisation CHOosing Interventions that are Cost-effective (WHO-CHOICE) defines three categories of cost-effectiveness based on a country’s GDP per QALY gained:
Highly cost-effective (less than GDP per capita);
Effectiveness (e.g. QALY gained) Cost (e.g. $) A. More costly, less effective B1. Less costly, less effective D. Less costly, more effective B2. Less costly, less effective C1. More costly, more effective C2. More costly, more effective
Lines of equal cost effectiveness (e.g. $ per QALY gained)
Threshold I Threshold II
Andrew Stafford BPharm(Hons) MPS AACPA
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Page 76 Cost-effective (between one and three times GDP per capita); and Not cost-effective (more than three times GDP per capita).185
These thresholds are by no means absolute with regards to most countries’ healthcare systems, including that of Australia. For example, Australian GDP per capita in 2008 was approximately $48 500. The Pharmaceutical Benefits Advisory Committee has recommended drugs for government subsidy at higher thresholds than $48 500 per QALY gained, although has been found to be unlikely to do so if the cost exceeded $76 000.186 In the UK, the National Institute for Health and Clinical Excellence (NICE) uses a threshold of £20 000 to £30 000 per QALY, and in the US, a threshold of US$ 50 000 to $100 000 per QALY is often is mentioned in medical literature.187 By not using explicit thresholds, a degree of arbitrariness is permitted, which may be more attractive to policy decision-makers.188
1.5 Conclusions
Having reviewed the relevant literature, it is apparent that firm conclusions about the efficacy, effectiveness and cost-effectiveness of HMRs cannot be made. Whilst there is considerable evidence that pharmacists identify and make recommendations to resolve or prevent DRPs in the high-risk populations investigated in most studies, the outcomes of them addressing DRPs in medication reviews is unclear. The results of the studies reviewed in this chapter have important ramifications for the Australian HMR program, in particular raising questions as to whether HMRs are realising the clinical and economic outcomes reported in the QUM evaluation studies. There is a clear need for research into the clinical and cost-effectiveness of HMRs. In particular, there is a need for a well-designed and detailed cost-effectiveness analysis.
1.6 Aims and objectives
Based on the literature, it was hypothesised that HMRs are not cost-effective compared to usual care; hence the overall aim of the research described in this thesis was to investigate the clinical and cost-effectiveness of HMRs. To achieve this aim, the following objectives were formulated and addressed:
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Page 77 To investigate novel methods for assessing the clinical and cost-effectivenessof HMRs;
To investigate the characteristics of the DRPs identified in HMRs, including the drugs and conditions involved, and the recommendations made to resolve or prevent DRPs;
To estimate the clinical effectiveness and cost-effectiveness of HMRs; and
To investigate potential avenues to optimise the clinical effectiveness and cost- effectiveness of HMRs.
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Page 78Chapter 2 - General methods
2.1 Overview
2.1.1 Study design
The study was initially conceived as a RCT, similar to that undertaken by Sorensen et al.66 Such a study would need to be powered sufficiently to detect changes in multiple health resource parameters over a period of at least 12 months. However, this approach presented several challenges. Firstly, in consideration of the number of parameters that would need to be measured per patient, data collection would have been extremely time-consuming. Secondly, as demonstrated by Holland et al.,26 in such studies, a small number of patients may incur large costs and skew the results. Similarly, the QUMCIT identified that the majority of cost savings resulting from HMRs were most likely to occur from reductions in hospitalisation in small numbers of patients.126
In consideration of this, the number of subjects required for a study to detect a conservative 10% reduction in hospitalisation in older adults was calculated. Burgess et al. identified that the annual hospitalisation rate due to ADEs in elderly Australians was approximately 12.9 per 1000 person-years in 2002.11 A RCT would therefore require over 1500 patients in both the intervention and control groups to detect a 10% reduction in hospitalisations resulting from ADRs at a power of 90% (P<0.05). However, only a portion of these hospitalisations are potentially preventable, so the actual sample size would need to be substantially larger. To further illustrate this issue, a cluster randomised, controlled multi-centre study of medication reviews in the Netherlands is currently underway.189 The sample size for this study was based on an assumption that medication review would reduce medication-related hospitalisation by 50%. The study aimed to enrol 14 200 patients who were randomised on a 1:1 basis to receive either medication review or usual care. Such a study was outside the scope of the available budget and timeline, as such it was concluded that an RCT was not a plausible design for the study.
A further complication was introduced by the widespread availability of HMRs limiting the recruitment of a suitable control group. Greenhill found that a HMR
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Page 79 performed for a patient of one GP may result in changes occurring in several other patients under that GP’s care, so randomisation undertaken on a per-patient patient basis was inappropriate.136 As a result, it would have been necessary to randomise patients per GP or GP practice, as had been done in several previous studies.64, 66 However, conducting the trial in this way would have necessitated some patients being ineligible to receive HMRs, which may potentially have been viewed as ethically questionable in consideration that there is some evidence of benefit.190These issues were not unique to the investigation of HMRs. To undertake any impact evaluation, an assessment of the consequences of patients not receiving the intervention is preferred. A related field in which RCTs are rarely, if ever, undertaken, involves clinical interventions performed during community pharmacy practice.191 A further concern in this field, in addition to ethical issues, is that pharmacists are professionally obliged to perform clinical interventions. Hence, it is not plausible to control studies of these interventions with a group that receives no intervention. Consequently, several previous studies have evaluated the potential clinical and economic outcomes of pharmacists’ clinical interventions through the use of expert opinion to estimate the counterfactual state, that is, what would have happened had the clinical interventions not occurred.192-201 In general, these studies involved experts predicting the health outcomes that would have occurred with and without the intervention to generate estimates of the effect of the intervention. A similar approach was taken in the QUMCIT and Sutherland project. In these studies, expert opinion was used to estimate the clinical outcomes and their associated costs to compare the effect of the intervention (the HMR) to the same patient not receiving the intervention.86, 126, 138-140
Consequently, an uncontrolled observational cohort study was undertaken, and the methodology used is described in detail on page 92. Briefly, four projects were undertaken to achieve the overall aim of the research described in this thesis. The first two studies involved evaluating the potential costs and QOL effects associated with specific DRPs. The outcomes of these two studies were then used to evaluate a sample of HMRs to estimate the clinical and economic outcomes resulting from HMRs. Finally, a sample of these HMRs were further analysed to identify potential predictors of cost- effectiveness. This is illustrated in Figure 5.
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Page 80 Clinical and economic evaluation of HMRs(Chapters 5 to 8)
HMR- accredited pharmacists enrolled in study (n=203 pharmacists)
HMR data submitted by 149 pharmacists (n=675 HMRs) Did not submit any HMRs (n=54 pharmacists)
Did not meet inclusion criteria (n=9 HMRs) Data unusable/incomplete (n=5 HMRs) HMR data that met inclusion criteria (n=661 HMRs)
Outcomes data available (n=560 HMRs) Outcomes data unavailable (n=101 HMRs) Outcomes assessed by
expert panel (n=180 HMRs)
Not assessed by expert panel (n=481 HMRs)
Investigation of factors related to the cost- effectiveness of HMRs (n=60 HMRs)
Evaluation of cost and QOL effects of DRPs (Chapters 3 and 4) Table of costs, health services and QOL effects resulting from DRPs Costs and health service utilisation evaluation
Hospitalisation costs and duration (obtained from literature search)
Non-hospitalisation costs and health services (developed from research project, 14 GPs)
Quality of life evaluation Obtained from literature search
Developed from research project (6 physicians)
FIGURE 1-FLOW CHART ILLUSTRATING RESEARCH STUDIES DESCRIBED IN THIS THESIS.DASHED LINES DELINEATE THE DISCRETE