Katherine Payne

Adapting clinical guidelines to take account of multimorbidity

Care of patients with multimorbidity could be improved if new technology is used to bring together guidelines on individual conditions and tailor advice to each patient’s circumstances, say Bruce Guthrie and colleagues

The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review

Abstract Objectives To assess the effectiveness of five gastroprotective strategies for people taking non-steroidal anti-inflammatory drugs (NSAIDs)—H2 receptor antagonists plus non-selective (or cyclo-oxygenase-1) NSAIDs; proton pump inhibitors plus non-selective NSAIDs; misoprostol plus non-selective NSAIDs; COX-2 selective NSAIDs; or COX-2 specific NSAIDs—in reducing serious gastrointestinal complications, symptomatic ulcers, serious cardiovascular or renal disease, and deaths, and improving quality of life. Data sources The Cochrane Library, Medline, Embase, Current Controlled Trials, and System for Information on Grey Literature in Europe (SIGLE) were searched to May 2002. Bibliographies and author contacts were used to identify further studies; non-English articles were included. Review methods Trial selection, data extraction, and quality assessment were performed independently, in duplicate. Articles were rejected only if the study was not a randomised controlled trial; did not assess a gastroprotective strategy versus placebo; included exclusively children or healthy volunteers; lasted less than 21 days; or no review outcomes were measured. Quality assessment included allocation concealment and baseline similarity. Random effects meta-analysis, meta-regression and subgrouping were used to pool effects and analyse associations with length of follow up, mean age, and baseline gastrointestinal status. Heterogeneity was examined and sensitivity analyses performed. Results Of 112 included randomised controlled trials (74 666 participants), five were judged to be at low risk of bias, and 138 deaths and 248 serious gastrointestinal events were reported overall. On comparing gastroprotective strategies versus placebo we found no evidence of effectiveness of H2 receptor antagonists for any primary outcomes (few events reported); proton pump inhibitors may reduce the risk of symptomatic ulcers (relative risk 0.09, 95% confidence interval 0.02 to 0.47); misoprostol reduces the risk of serious gastrointestinal complications (0.57, 0.36 to 0.91) and symptomatic ulcers (0.36, 0.20 to 0.67); COX-2 selectives reduce the risk of symptomatic ulcers (0.41, 0.26 to 0.65) and COX-2 specifics reduce the risk of symptomatic ulcers (0.49, 0.38 to 0.62) and possibly serious gastrointestinal complications (0.55, 0.38 to 0.80). All strategies except COX-2 selectives reduce the risk of endoscopic ulcers (at least 3 mm in diameter). Conclusions Misoprostol, COX-2 specific and selective NSAIDs, and probably proton pump inhibitors significantly reduce the risk of symptomatic ulcers, and misoprostol and probably COX-2 specifics significantly reduce the risk of serious gastrointestinal complications, but data quality is low. More data on H2 receptor antagonists and proton pump inhibitors are needed, as is better reporting of rare but important outcomes.

Patient empowerment: The need to consider it as a measurable patient-reported outcome for chronic conditions

BackgroundHealth policy in the UK and elsewhere is prioritising patient empowerment and patient evaluations of healthcare. Patient reported outcome measures now take centre-stage in implementing strategies to increase patient empowerment. This article argues for consideration of patient empowerment itself as a directly measurable patient reported outcome for chronic conditions, highlights some issues in adopting this approach, and outlines a research agenda to enable healthcare evaluation on the basis of patient empowerment.DiscussionPatient empowerment is not a well-defined construct. A range of condition-specific and generic patient empowerment questionnaires have been developed; each captures a different construct e.g. personal control, self-efficacy/self-mastery, and each is informed by a different implicit or explicit theoretical framework. This makes it currently problematic to conduct comparative evaluations of healthcare services on the basis of patient empowerment. A case study (clinical genetics) is used to (1) illustrate that patient empowerment can be a valued healthcare outcome, even if patients do not obtain health status benefits, (2) provide a rationale for conducting work necessary to tighten up the patient empowerment construct (3) provide an exemplar to inform design of interventions to increase patient empowerment in chronic disease. Such initiatives could be evaluated on the basis of measurable changes in patient empowerment, if the construct were properly operationalised as a patient reported outcome measure. To facilitate this, research is needed to develop an appropriate and widely applicable generic theoretical framework of patient empowerment to inform (re)development of a generic measure. This research should include developing consensus between patients, clinicians and policymakers about the content and boundaries of the construct before operationalisation. This article also considers a number of issues for society and for healthcare providers raised by adopting the patient empowerment paradigm.SummaryHealthcare policy is driving the need to consider patient empowerment as a measurable patient outcome from healthcare services. Research is needed to (1) tighten up the construct (2) develop consensus about what is important to include (3) (re)develop a generic measure of patient empowerment for use in evaluating healthcare (4) understand if/how people make trade-offs between empowerment and gain in health status.

Economic methods for valuing the outcomes of genetic testing: beyond cost-effectiveness analysis.

Genetic testing in health care can provide information to help with disease prediction, diagnosis, prognosis, and treatment. Assessing the clinical utility of genetic testing requires a process to value and weight different outcomes. This article discusses the relative merits of different economic measures and methods to inform recommendations relative to genetic testing for risk of disease, including cost-effectiveness analysis and cost-benefit analysis. Cost-effectiveness analyses refer to analyses that calculate the incremental cost per unit of health outcomes, such as deaths prevented or life-years saved because of some intervention. Cost-effectiveness analyses that use preference-based measures of health state utility such as quality-adjusted life-years to define outcomes are referred to as cost-utility analyses. Cost-effectiveness analyses presume that health policy decision makers seek to maximize health subject to resource constraints. Cost-benefit analyses can incorporate monetary estimates of willingness-to-pay for genetic testing, including the perceived value of information independent of health outcomes. These estimates can be derived from contingent valuation or discrete choice experiments. Because important outcomes of genetic testing do not fit easily within traditional measures of health, cost-effectiveness analyses do not necessarily capture the full range of outcomes of genetic testing that are important to decision makers and consumers. We recommend that health policy decision makers consider the value to consumers of information and other nonhealth attributes of genetic testing strategies.

Current use of pharmacogenetic testing : a national survey of thiopurine methyltransferase testing prior to azathioprine prescription

Background:  Azathioprine is an immunosuppressant prescribed for the treatment of inflammatory conditions and after organ transplantation. Risk of neutropaenia has limited the effective use of azathioprine (AZA) and driven requirements for careful monitoring and blood tests. Thiopurine methyltransferase (TPMT) is a genetically moderated key enzyme involved in the metabolism of AZA that can be used to stratify individuals into different levels of risk of developing neutropaenia. Two techniques can be used to measure TPMT status: enzyme‐level testing (phenotype testing) and DNA based testing (genotype testing).

Drug-disease and drug-drug interactions: systematic examination of recommendations in 12 UK national clinical guidelines

Objective To identify the number of drug-disease and drug-drug interactions for exemplar index conditions within National Institute of Health and Care Excellence (NICE) clinical guidelines. Design Systematic identification, quantification, and classification of potentially serious drug-disease and drug-drug interactions for drugs recommended by NICE clinical guidelines for type 2 diabetes, heart failure, and depression in relation to 11 other common conditions and drugs recommended by NICE guidelines for those conditions. Setting NICE clinical guidelines for type 2 diabetes, heart failure, and depression Main outcome measures Potentially serious drug-disease and drug-drug interactions. Results Following recommendations for prescription in 12 national clinical guidelines would result in several potentially serious drug interactions. There were 32 potentially serious drug-disease interactions between drugs recommended in the guideline for type 2 diabetes and the 11 other conditions compared with six for drugs recommended in the guideline for depression and 10 for drugs recommended in the guideline for heart failure. Of these drug-disease interactions, 27 (84%) in the type 2 diabetes guideline and all of those in the two other guidelines were between the recommended drug and chronic kidney disease. More potentially serious drug-drug interactions were identified between drugs recommended by guidelines for each of the three index conditions and drugs recommended by the guidelines for the 11 other conditions: 133 drug-drug interactions for drugs recommended in the type 2 diabetes guideline, 89 for depression, and 111 for heart failure. Few of these drug-disease or drug-drug interactions were highlighted in the guidelines for the three index conditions. Conclusions Drug-disease interactions were relatively uncommon with the exception of interactions when a patient also has chronic kidney disease. Guideline developers could consider a more systematic approach regarding the potential for drug-disease interactions, based on epidemiological knowledge of the comorbidities of people with the disease the guideline is focused on, and should particularly consider whether chronic kidney disease is common in the target population. In contrast, potentially serious drug-drug interactions between recommended drugs for different conditions were common. The extensive number of potentially serious interactions requires innovative interactive approaches to the production and dissemination of guidelines to allow clinicians and patients with multimorbidity to make informed decisions about drug selection.

Challenges in the Development and Reimbursement of Personalized Medicine—Payer and Manufacturer Perspectives and Implications for Health Economics and Outcomes Research: A Report of the ISPOR Personalized Medicine Special Interest Group

BACKGROUND Personalized medicine technologies can improve individual health by delivering the right dose of the right drug to the right patient at the right time but create challenges in deciding which technologies offer sufficient value to justify widespread diffusion. Personalized medicine technologies, however, do not neatly fit into existing health technology assessment and reimbursement processes. OBJECTIVES In this article, the Personalized Medicine Special Interest Group of the International Society for Pharmacoeconomics and Outcomes Research evaluated key development and reimbursement considerations from the payer and manufacturer perspectives. METHODS Five key areas in which health economics and outcomes research best practices could be developed to improve value assessment, reimbursement, and patient access decisions for personalized medicine have been identified. RESULTS These areas are as follows: 1 research prioritization and early value assessment, 2 best practices for clinical evidence development, 3 best practices for health economic assessment, 4 addressing health technology assessment challenges, and 5 new incentive and reimbursement approaches for personalized medicine. CONCLUSIONS Key gaps in health economics and outcomes research best practices, decision standards, and value assessment processes are also discussed, along with next steps for evolving health economics and outcomes research practices in personalized medicine.

Outcome measurement in clinical genetics services: a systematic review of validated measures.

OBJECTIVE This systematic review aimed to inform researchers and policymakers about what validated outcome measures are available to evaluate clinical genetics services (CGS) and the need for new measures. METHODS Validated outcome measures used to evaluate CGS were identified from a systematic literature review. Subjective outcome measures were assumed to have been validated only if some form of psychometric assessment was reported. RESULTS A total of 1688 titles and abstracts were identified, and 61 articles met the inclusion criteria for the final review, which covered 67 validated outcome measures. There were 37 nongenetics-specific and 30 genetics-specific measures identified. No single validated outcome measure encompassed all potential patient benefits from using a CGS. A variety of different domains were identified, including anxiety and depression, coping, decision-making, distress, family environment, health status, knowledge, mood, perception of risk, perceived personal control, psychological impact, quality of life, satisfaction and expectations, self-esteem, spiritual well-being, and worry. Some important aspects of patient benefit from CGS are not covered by existing outcome measures. CONCLUSIONS New research is necessary to develop the array of outcome measures required to quantify the benefits CGS offer patients living with the effects of genetic conditions. These need to be suitable for use in prospective evaluation studies to provide robust evidence for decision-makers to inform service development and commissioning. This includes prioritization of the existing validated outcome measures in terms of their usefulness and relevance to the measurement and valuation of patient benefits from a CGS.

Are patients with intermediate TPMT activity at increased risk of myelosuppression when taking thiopurine medications

UNLABELLED Thiopurine S-methyltransferase (TPMT) metabolizes thiopurine medications, including azathioprine and 6-mercaptopurine. Absent TPMT activity (i.e., in individuals homozygous for a variant TPMT allele) is associated with an increased risk of myelosuppression in patients taking thiopurine drugs. However, it is not clear if there is also an increased risk for patients with intermediate TPMT activity (i.e., in individuals heterozygous for a variant TPMT allele). AIMS To quantify the increased risk of myelosuppression for patients with intermediate TPMT activity. MATERIALS & METHODS A systematic review identified published studies, up to 29 September 2008, that explored the relationship between TMPT and hematological adverse drug reactions to thiopurines. Following a critical appraisal of the quality of published studies, a meta-analysis calculated the odds ratio of myelosuppression for patients with intermediate TPMT activity compared with wild-type. RESULTS A total of 67 studies were identified, the majority retrospective cohort in design. Patients with two TPMT variant alleles who are TPMT deficient have a substantial increase in their risk of myelotoxicity (86% of deficient patients developed myelosuppression). The increase in odds ratio of developing leukopenia for patients with intermediate TPMT activity or one TPMT variant allele compared with wild-type was 4.19 (95% CI: 3.20-5.48). CONCLUSION This meta-analysis suggests that individuals with both intermediate and absent TPMT activity have an increased risk of developing thiopurine-induced myelosuppression, compared with individuals with normal activity. However, there is significant variability in the quality of the reported studies and large prospective studies to clarify the size of the effect of TPMT variant alleles on the risk of myelosuppression should be conducted. Accurate risk assessments will provide important data to inform clinical guidelines.

Patient empowerment in clinical genetics services.

Outcome measurement in clinical genetics is problematic because the patient benefits are difficult to measure. The aim in this qualitative grounded theory study was to develop a theoretical framework describing the patient benefits from using clinical genetics services. Seven focus groups and 19 interviews were conducted with patients, patient group representatives, and health professionals. Data analysis resulted in construction of a model of empowerment summarizing the patient benefits from using clinical genetics services. Empowerment is similar to the concept of perceived personal control (PPC), and a measure of PPC has been developed for use in evaluations of clinical genetics services. However, empowerment includes some benefits not captured by PPC related to empowerment of other at risk relatives, and future generations.