The study was conducted in accordance with all applicable regulatory requirements, with the Guidelines for Good Pharmacoepidemiology Practices, 9 all applicable patient privacy requirements and the guiding principles of the Declaration of Helsinki. The matched IC and IC-free cohorts were followed up from the index date until the earliest of the following events: transfer out of the practice date, the last GP practice collections date, death date or the end of the study.
This is a retrospective database analysis carried out following ethical committee approval. No patient or the public was involved in the study design or in the recruitment or the conduct of this study. No specific dissemination of study results to participants was done. However, we provided a lay language summary contextualising the results and potential clinical research relevance and impact in figure 1.
These were then summed over all resource use categories to obtain a total cost for each patient. For each patient, the cost of each prescription was calculated by merging the product code, package type and prescribed quantity with the associated standard package size and unit cost. The unit cost of a product in a prescription instance ie, one distinct record in the CPRD therapy was calculated using the cost described in the British National Formulary BNF , as listed price if included or indicative price based on price in BNF.
Ambulatory visits included consultations with GPs and nurses in primary or community care. Visits included consultations at the practice or at the home of the patient, during working hours and out of hours. Consultations for which no clinical intervention was recorded were not included in the cost estimate for GP practice related healthcare utilisation, for example: information technology data migration, administrative recording of received information. Administrative resource use in primary care was considered, including time on the phone, writing reports, referrals, etc.
Hospital Outpatient resource utilisation concerned HZ related referrals for non-inpatient hospital consultations, derived from the HES Outpatient data. Further details, including information on the IC populations included, ICD codes for HZ and PHN, and unit healthcare costs are provided in the online supplementary material , specifically in online supplementary tables 1 to 4. The age distribution of matched cohorts was: 18—44 YOA Hospital admissions over the longer follow-up period of 7 days prior to days post initial HZ onset Panel B were similar to those of the shorter follow-up period Panel A over all age groups.
Multiple HZ-related hospital visits were reported for some individuals. The mean number of hospitalizations per HZ case for the day analysis was, 0. A similar pattern of higher healthcare resource utilisation with increasing age and in IC individuals was observed for all resources for which costs were assigned. A similar mean number of sick leave certificates were observed between the IC and the IC-free cohorts with the mean decreasing with age.
The costs increase with age and are consistently higher in the IC cohort compared with the IC-free cohort. It is also noteworthy that the means are consistently higher than medians, and as is common for healthcare cost data, the distribution is skewed to the right. See online supplementary table 5 and online supplementary figures 1 and 2 provide additional data on healthcare Costs for the analysis period 7 days prior to 90 days post initial HZ onset.
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For all IC conditions, the costs were higher than those for the IC-free group, in particular for the hematopoietic stem cell transplantation HSCT , haematological malignancies and solid organ transplantations SOT conditions. In general, there was a similar trend of increasing costs with increasing age-groups.
A few outliers were observed due to small sample sizes. Similarly, in total only and individuals with autoimmune thyroiditis and SOT were included, respectively. Table 3 presents the mean healthcare costs by IC status and HZ complication status. The mean healthcare costs were approximately 4 to 5 times higher for individuals with PHN for the analysis period 7 days prior to days compared with individuals with HZ only.
Similarly, mean healthcare costs were approximately 2 to 4 times higher for individuals with HZ complications compared with individuals with HZ only. Online supplementary table 6 presents the non-HZ related hospital inpatient stay for the period 7 days to days post initial-HZ onset. The mean number of non-HZ related hospitalisations were consistently higher in IC patients compared with and IC-free patients and increased with age. In this study, we presented the healthcare resource utilisation and costs associated with HZ in both IC and IC-free populations using large electronic health record databases in the UK.
An important feature of this study was that the design enabled the calculation of IC condition prevalence rates, HZ incidence rates and occurrence of HZ-related healthcare utilisation and costs at individual level in the same predefined population s , see Yanni et al for further detail on epidemiological outcomes. Similarly, only medications potentially related to HZ treatment were included see online supplementary tables 2 and 4.
Our study aimed to include only medications considered to be directly related to HZ; that is, excluded medications that may be linked to IC conditions eg, aspirin, analgesic creams as they could be used primarily to reduce pain from other conditions. This restriction and the introduction of generic versions of medications such as acyclovir, gabapentin and derivatives of gabapentin which resulted in lower prices, contributed to the reduced overall medication costs reported in this study.
Many studies on HCRU and costs include a number of days prior to diagnosis, for example, 14 or 21 days, as there may be a delay in diagnosis and HCRU may be used prior to diagnosis. The costs of PHN were analysed over two time-periods, ie, 1 7 days prior to 90 days post HZ onset and 2 7 days prior to days post HZ onset. The rationale for the time periods studied was that using analysis period 1 alone could lead to an underestimation of PHN costs whereas using analysis period 2 only could overestimate these costs.
The most frequently used definition of PHN is: pain persisting or appearing at least 90 days following rash onset. The median duration of PHN has been reported to be The healthcare costs associated with PHN and complications were higher than those for individuals with HZ only. However, as reported elsewhere, when considering the overall cost of disease at a population level, the overall healthcare-associated cost is higher for HZ only.
Few studies have investigated healthcare resource utilisation and costs in IC individuals. Schroder et al carried out a study using the German Pharmacoepidemiological Research Database, which consists of claims data from four statutory health insurances. Insurance databases include not only the healthcare resource utilisation but also costs. As such the overall costs need to be calculated by assigning unit costs to the resource utilisation. There are advantages however of using the CPRD and HES in that the databases offer more diversity than might be observed using insurance databases, the latter of which may be somewhat limited by bias associated with factors such as age, race and income.
This study has several limitations. Diagnoses were derived from administrative codes, which are recognised to be subject to miscoding or under-coding and are not validated against medical charts. In addition, many IC individuals had prescriptions that included more than one immunosuppressing medicine. In this study we selected 16 IC conditions in our definition of an IC population but perhaps other researchers would select different IC conditions. As such our study is exploratory in nature and was not intended to be definitive. Immunosuppression is known to be associated with an increased risk of HZ in the UK.
Gregory Collet coordinated manuscript development and editorial support. Kathleen Daly provided editing support. However, the interpretation and conclusions contained in this report are those of the authors alone. Part of the data have been previously published as an abstract Curran al. All named authors provided substantial intellectual and scientific input during the manuscript development, critically reviewing the content, revising the manuscript and giving final approval before submission. The work described was carried out in accordance with the ICMJE recommendations for conducting, reporting, editing and publishing scholarly work in medical journals.
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