Colin Ridyard

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.

Resource-Use Measurement Based on Patient Recall: Issues and Challenges for Economic Evaluation

Accurate resource-use measurement is challenging within an economic evaluation, but is a fundamental requirement for estimating efficiency. Considerable research effort has been concentrated on the appropriate measurement of outcomes and the policy implications of economic evaluation, while methods for resource-use measurement have been relatively neglected. Recently, the Database of Instruments for Resource Use Measurement (DIRUM) was set up at http://www.dirum.org to provide a repository where researchers can share resource-use measures and methods. A workshop to discuss the issues was held at the University of Birmingham in October 2011. Based on material presented at the workshop, this article highlights the state of the art of UK instruments for resource-use data collection based on patient recall. We consider methodological issues in the design and analysis of resource-use instruments, and the challenges associated with designing new questionnaires. We suggest a method of developing a good practice guideline, and identify some areas for future research. Consensus amongst health economists has yet to be reached on many aspects of resource-use measurement. We argue that researchers should now afford costing methodologies the same attention as outcome measurement, and we hope that this Current Opinion article will stimulate a debate on methods of resource-use data collection and establish a research agenda to improve the precision and accuracy of resource-use estimates.

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.

Conducting Economic Evaluations Alongside Randomised Trials: Current Methodological Issues and Novel Approaches

Trial-based economic evaluations are an important aspect of health technology assessment. The availability of patient-level data coupled with unbiased estimates of clinical outcomes means that randomised controlled trials are effective vehicles for the generation of economic data. However there are methodological challenges to trial-based evaluations, including the collection of reliable data on resource use and cost, choice of health outcome measure, calculating minimally important differences, dealing with missing data, extrapolating outcomes and costs over time and the analysis of multinational trials. This review focuses on the state of the art of selective elements regarding the design, conduct, analysis and reporting of trial-based economic evaluations. The limitations of existing approaches are detailed and novel methods introduced. The review is internationally relevant but with a focus towards practice in the UK.

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.

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

BackgroundSubcutaneous 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.ObjectiveOur 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.MethodsNine 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.ResultsOf 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.ConclusionsThe 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.

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.

Core items for a standardized resource-use measure (ISRUM): expert Delphi consensus survey

Background Resource use measurement by patient recall is characterized by inconsistent methods and a lack of validation. A validated standardized resource use measure could increase data quality, improve comparability between studies, and reduce research burden. Objectives To identify a minimum set of core resource use items that should be included in a standardized adult instrument for UK health economic evaluation from a provider perspective. Methods Health economists with experience of UK-based economic evaluations were recruited to participate in an electronic Delphi survey. Respondents were asked to rate 60 resource use items (e.g., medication names) on a scale of 1 to 9 according to the importance of the item in a generic context. Items considered less important according to predefined consensus criteria were dropped and a second survey was developed. In the second round, respondents received the median score and their own score from round 1 for each item alongside summarized comments and were asked to rerate items. A final project team meeting was held to determine the recommended core set. Results Forty-five participants completed round 1. Twenty-six items were considered less important and were dropped, 34 items were retained for the second round, and no new items were added. Forty-two respondents (93.3%) completed round 2, and greater consensus was observed. After the final meeting, 10 core items were selected, with further items identified as suitable for “bolt-on” questionnaire modules. Conclusions The consensus on 10 items considered important in a generic context suggests that a standardized instrument for core resource use items is feasible.

Identification Of Items For A Standardised Resource-Use Measure: Review Of Current Instruments.

Methods A single version of each instrument designed for use in a UK-based study was identified from the Database of Instruments for Resource-Use Measurement (http://www.dirum. org). Section headings (‘domains’) and questions (‘items’) were extracted verbatim according to a predefined schema. Information on the recall period, level of detail, use of skip logic and scope (disease-specific or total resource use) was also extracted. Items were scrutinised for overlap.

Review of the use of resource use instruments based on patient recall in relation to other methods of resource use estimation

Background We conducted a review of articles citing trial-related resource use measures catalogued in the Database of Instruments for Resource Use Measurement (http:// www.DIRUM.org). The aims were to assess: (i) how the instruments were used in practice; (ii) which items of resource use were most frequently measured using patient-recall; and (iii) how estimates compared if more than one method of data collection was used for the same resource items