Factors Influencing the Cost-Effectiveness Outcomes of HPV Vaccination and Screening Interventions in Low-to-Middle-Income Countries (LMICs): A Systematic Review.

BACKGROUND: Cervical cancer ranks fourth amongst the commonest malignancies worldwide and the second most prevalent cancer afflicting women in low-to-middle income countries (LMICs), hence, of great public health importance. LMICs are the most affected regions as evidenced by their high prevalence of the disease. Mortality associated with cervical neoplasms is preventable through the implementation of recommended preventive approaches. AIMS: This review aimed to appraise evidence on the cost effectiveness of cervical cancer prevention interventions in LMICs involving cervical screening and human papilloma virus (HPV) vaccination programmes. METHODS: A search of CINAHL, MEDLINE, PubMed, and Web of Science was elicited and studies published between 1st January 2008 and 31st December 2018 were retrieved. Two authors independently undertook the screening, review, selection of studies, and data extraction with disagreements being resolved through discussion and consensus. RESULTS: Twelve studies were selected. The cost-effectiveness outcomes of HPV vaccination and screening interventions are dependent on age, screening method used, intervention coverage, and the number of doses or visits required for vaccination and screening, respectively. A combination of visual inspection with acetic acid (VIA) screening and HPV vaccination appears to be the most cost-effective approach in reducing the lifetime risk for HPV-linked cervical neoplasms. Similarly, vaccination as a stand-alone intervention is potentially cost effective provided the coverage is maintained between 70 and 100%. CONCLUSIONS: HPV vaccination and screening interventions may be cost effective in LMICs and potentially reduce the lifetime risk, economic burden, and associated mortality. However, it is important to consider the factors that influence the cost effectiveness of cervical cancer prevention interventions for better outcomes to be realised.

Cost-Effectiveness of Pediatric Central Venous Catheters in the UK: A Secondary Publication from the CATCH Clinical Trial.

Background: Antibiotic-impregnated central venous catheters (CVCs) reduce the risk of bloodstream infections (BSIs) in patients treated in pediatric intensive care units (PICUs). However, it is unclear if they are cost-effective from the perspective of the National Health Service (NHS) in the UK. Methods: Economic evaluation alongside the CATCH trial (ISRCTN34884569) to estimate the incremental cost effectiveness ratio (ICER) of antibiotic-impregnated (rifampicin and minocycline), heparin-bonded and standard polyurethane CVCs. The 6-month costs of CVCs and hospital admissions and visits were determined from administrative hospital data and case report forms. Results: BSIs were detected in 3.59% (18/502) of patients randomized to standard, 1.44% (7/486) to antibiotic and 3.42% (17/497) to heparin CVCs. Lengths of hospital stay did not differ between intervention groups. Total mean costs (95% confidence interval) were: £45,663 (£41,647-£50,009) for antibiotic, £42,065 (£38,322-£46,110) for heparin, and £44,503 (£40,619-£48,666) for standard CVCs. As heparin CVCs were not clinically effective at reducing BSI rate compared to standard CVCs, they were considered not to be cost-effective. The ICER for antibiotic vs. standard CVCs, of £54,057 per BSI avoided, was sensitive to the analytical time horizon. Conclusions: Substituting standard CVCs for antibiotic CVCs in PICUs will result in reduced occurrence of BSI but there is uncertainty as to whether this would be a cost-effective strategy for the NHS.

CATheter Infections in CHildren (CATCH): a randomised controlled trial and economic evaluation comparing impregnated and standard central venous catheters in children.

BACKGROUND: Impregnated central venous catheters (CVCs) are recommended for adults to reduce bloodstream infection (BSI) but not for children. OBJECTIVE: To determine the effectiveness of impregnated compared with standard CVCs for reducing BSI in children admitted for intensive care. DESIGN: Multicentre randomised controlled trial, cost-effectiveness analysis from a NHS perspective and a generalisability analysis and cost impact analysis. SETTING: 14 English paediatric intensive care units (PICUs) in England. PARTICIPANTS: Children aged < 16 years admitted to a PICU and expected to require a CVC for ≥ 3 days. INTERVENTIONS: Heparin-bonded, antibiotic-impregnated (rifampicin and minocycline) or standard polyurethane CVCs, allocated randomly (1 : 1 : 1). The intervention was blinded to all but inserting clinicians. MAIN OUTCOME MEASURE: Time to first BSI sampled between 48 hours after randomisation and 48 hours after CVC removal. The following data were used in the trial: trial case report forms; hospital administrative data for 6 months pre and post randomisation; and national-linked PICU audit and laboratory data. RESULTS: In total, 1859 children were randomised, of whom 501 were randomised prospectively and 1358 were randomised as an emergency; of these, 984 subsequently provided deferred consent for follow-up. Clinical effectiveness - BSIs occurred in 3.59% (18/502) of children randomised to standard CVCs, 1.44% (7/486) of children randomised to antibiotic CVCs and 3.42% (17/497) of children randomised to heparin CVCs. Primary analyses comparing impregnated (antibiotic and heparin CVCs) with standard CVCs showed no effect of impregnated CVCs [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.37 to 1.34]. Secondary analyses showed that antibiotic CVCs were superior to standard CVCs (HR 0.43, 95% CI 0.20 to 0.96) but heparin CVCs were not (HR 1.04, 95% CI 0.53 to 2.03). Time to thrombosis, mortality by 30 days and minocycline/rifampicin resistance did not differ by CVC. Cost-effectiveness - heparin CVCs were not clinically effective and therefore were not cost-effective. The incremental cost of antibiotic CVCs compared with standard CVCs over a 6-month time horizon was £1160 (95% CI -£4743 to £6962), with an incremental cost-effectiveness ratio of £54,057 per BSI avoided. There was considerable uncertainty in costs: antibiotic CVCs had a probability of 0.35 of being dominant. Based on index hospital stay costs only, antibiotic CVCs were associated with a saving of £97,543 per BSI averted. The estimated value of health-care resources associated with each BSI was £10,975 (95% CI -£2801 to £24,751). Generalisability and cost-impact - the baseline risk of BSI in 2012 for PICUs in England was 4.58 (95% CI 4.42 to 4.74) per 1000 bed-days. An estimated 232 BSIs could have been averted in 2012 using antibiotic CVCs. The additional cost of purchasing antibiotic CVCs for all children who require them (£36 per CVC) would be less than the value of resources associated with managing BSIs in PICUs with standard BSI rates of > 1.2 per 1000 CVC-days. CONCLUSIONS: The primary outcome did not differ between impregnated and standard CVCs. However, antibiotic-impregnated CVCs significantly reduced the risk of BSI compared with standard and heparin CVCs. Adoption of antibiotic-impregnated CVCs could be beneficial even for PICUs with low BSI rates, although uncertainty remains whether or not they represent value for money to the NHS. Limitations - inserting clinicians were not blinded to allocation and a lower than expected event rate meant that there was limited power for head-to-head comparisons of each type of impregnation. Future work - adoption of impregnated CVCs in PICUs should be considered and could be monitored through linkage of electronic health-care data and clinical data on CVC use with laboratory surveillance data on BSI. TRIAL REGISTRATION: ClinicalTrials.gov NCT01029717. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 18. See the NIHR Journals Library website for further project information.

A Systematic Review of Patients' Perspectives on the Subcutaneous Route of Medication Administration.

BACKGROUND: Subcutaneous injections allow for self-administration, but consideration of patients' perspectives on treatment choice is important to ensure adherence. Previous systematic reviews have been limited in their scope for assessing preferences in relation to other routes of administration. OBJECTIVE: Our objective was to examine patients' perspectives on subcutaneously administered self-injectable medications when compared with other routes or methods of administration for the same medicines. METHODS: Nine electronic databases were searched for publications since 2000 using terms pertaining to methods of administration, choice behavior, and adverse effects. Eligibility for inclusion was determined through reference to specific criteria by two independent reviewers. Results were described narratively. RESULTS: Of the 1726 papers screened, 85 met the inclusion criteria. Studies were focused mainly on methods of insulin administration for diabetes but also included treatments for pediatric growth disorders, multiple sclerosis, HIV, and migraine. Pen devices and autoinjectors were favored over administration with needle and syringe, particularly with respect to ergonomics, convenience, and portability. Inhalation appeared to be more acceptable than subcutaneous injection (in the case of insulin), but how subcutaneous infusion, intramuscular injection, and needle-free injection devices compare with subcutaneous injections in terms of patient preference is less certain. CONCLUSIONS: The review identified a number of studies showing the importance of the methods and routes of drug delivery on patient choice. However, studies were prone to bias, and further robust evidence based on methodologically sound approaches is required to demonstrate how patient choice might translate to improved adherence.

Study protocol for a randomised controlled trial of insulin delivery by continuous subcutaneous infusion compared to multiple daily injections.

BACKGROUND: Intensive insulin therapy with continuous subcutaneous insulin infusion (CSII) devices or multiple daily injections (MDI) reduces the risk of long-term vascular complications of type I diabetes (TID). Both treatments are used routinely, but there is little evidence to demonstrate superiority of either treatment. If CSII treatment reduces the risk of long-term complications or is associated with an improved quality of life (QoL), the additional cost of this therapy may be compensated for by a reduction in long-term health expenditure. If there is no demonstrable difference between treatments, health-care resources may be better invested elsewhere. This study aims to address this gap in knowledge. METHODS/DESIGN: This is a pragmatic, randomised controlled trial (RCT). Fifteen centres, selected to represent a population with a broad demographic, will recruit 316 patients, newly diagnosed with TID, aged between 7 months and 15 years. Exclusion criteria include additional pathologies or treatments likely to affect glycaemic control and a first-degree relative with TID. Randomisation to CSII or MDI is stratified for age, gender and recruiting centre. The randomised treatment starts within 15 days of diagnosis. Patients will be trained to adjust their insulin dose according to carbohydrate intake and blood glucose level. Study visits coincide with routine clinic appointments at 3, 6, 9 and 12 months when data relating to routine clinical assessments, adverse events and concomitant medications are collected. Health utilities questionnaires are completed at each visit and a diabetes-specific QoL questionnaire (PedsQL) at diagnosis, 6 and 12 months. The primary outcome is glycaemic control (HbA1c) at 12 months. Secondary outcome measures include QoL, insulin use, growth and weight gain, adverse events and a health economics appraisal. DISCUSSION: This is the first adequately powered RCT comparing CSII and MDI in a non-selected population, treated according to standard practice guidelines. It will produce data that are meaningful to individual patients and local and national policymakers. TRIAL REGISTRATION: The study was registered with the European Clinical Trials Database on 4 November 2010, reference 2010-023792-25.

Taxonomy for methods of resource use measurement.

Resource use measures, including forms, diaries and questionnaires, are ubiquitous in trial-based economic evaluations in the UK. However, there are concerns about the accuracy of how they are described, which limits the transparency of reporting. We developed a simple and structured taxonomy for methods of resource use measurement by examining 94 resource use measures (RUMs) employed within clinical trials, conducting a descriptive synthesis of the extracted data and soliciting wider opinion during a period of consultation. The reporting of RUMs was found to be varied and inconsistent. Our new taxonomy, which considered the views of 20 consultees, requires that RUMs are reported with a description of the following: (i) the source of data (patient; patient proxy, e.g. carer, parent or guardian; observation of contemporary events; medical records; or other databases); (ii) who completes the RUM (patient or their proxy, and researcher or health care professional); (iii) how it is administered (to self [the patient], face to face or telephone); (iv) how it is recorded (form, questionnaire, log or diary); and (v) medium of recording (e.g. paper or electronically). Based on the present analysis, we have developed a taxonomy for RUMs that should result in data collection methods being described more accurately.

Development of a database of instruments for resource-use measurement: purpose, feasibility, and design.

BACKGROUND: Health economists frequently rely on methods based on patient recall to estimate resource utilization. Access to questionnaires and diaries, however, is often limited. This study examined the feasibility of establishing an open-access Database of Instruments for Resource-Use Measurement, identified relevant fields for data extraction, and outlined its design. METHODS: An electronic survey was sent to authors of full UK economic evaluations listed in the National Health Service Economic Evaluation Database (2008-2010), authors of monographs of Health Technology Assessments (1998-2010), and subscribers to the JISCMail health economics e-mailing list. The survey included questions on piloting, validation, recall period, and data capture method. Responses were analyzed and data extracted to generate relevant fields for the database. RESULTS: A total of 143 responses to the survey provided data on 54 resource-use instruments for inclusion in the database. All were reliant on patient or carer recall, and a majority (47) were questionnaires. Thirty-seven were designed for self-completion by the patient, carer, or guardian, and the remainder were designed for completion by researchers or health care professionals while interviewing patients. Methods of development were diverse, particularly in areas such as the planning of resource itemization (evident in 25 instruments), piloting (25), and validation (29). CONCLUSION: On the basis of the present analysis, we developed a Web-enabled Database of Instruments for Resource-Use Measurement, accessible via www.DIRUM.org. This database may serve as a practical resource for health economists, as well as a means to facilitate further research in the area of resource-use data collection.

Methods for the collection of resource use data within clinical trials: a systematic review of studies funded by the UK Health Technology Assessment program.

BACKGROUND: The UK Health Technology Assessment (HTA) program funds trials that address issues of clinical and cost-effectiveness to meet the needs of the National Health Service (NHS). The objective of this review was to systematically assess the methods of resource use data collection and costing; and to produce a best practice guide for data capture within economic analyses alongside clinical trials. METHODS: All 100 HTA-funded primary research papers published to June 2009 were reviewed for the health economic methods employed. Data were extracted and summarized by: health technology assessed, costing perspective adopted, evidence of planning and piloting, data collection method, frequency of data collection, and sources of unit cost data. RESULTS: Ninety-five studies were identified as having conducted an economic analysis, of which 85 recorded patient-level resource use. The review identified important differences in how data are collected. These included: a priori evidence of analysts having identified important cost drivers; the piloting and validation of patient-completed resource use questionnaires; choice of costing perspective; and frequency of data collection. Areas of commonality included: the extensive use of routine medical records and reliance on patient recall; and the use of standard sources of unit costs. CONCLUSION: Economic data collection is variable, even among a homogeneous selection of trials designed to meet the needs of a common organization (NHS). Areas for improvement have been identified, and based on our findings and related reviews and guidelines, a checklist is proposed for good practice relating to economic data collection within clinical trials.