Julie Jones-Diette

Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview

BACKGROUND Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. METHODS We examined these methodological challenges through a pragmatic review of the available literature. RESULTS Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. CONCLUSION Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented.

Interventions for hyperhidrosis in secondary care:a systematic review and value-of-information analysis

BACKGROUND Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. OBJECTIVE To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. METHODS A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. RESULTS AND CONCLUSIONS Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. LIMITATIONS The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. FUTURE WORK Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses. STUDY REGISTRATION This study is registered as PROSPERO CRD42015027803. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Interventional Management of Hyperhidrosis in Secondary Care: A Systematic Review

Hyperhidrosis is uncontrollable excessive sweating, which occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life.

Hyperhidrosis Quality of Life Measures : Review and Patient Perspective

Abstract Purpose: To identify the tools that have been used to measure quality of life in hyperhidrosis research and obtain patient insight on commonly used tools. Methods: Twelve databases were searched to identify studies that reported measuring quality of life or described a quality of life tool in the context of hyperhidrosis. Data on the use of the tools were tabulated and hyperhidrosis-specific and dermatology-specific measures were summarized. A workshop was held to obtain the patients’ perspective on the most commonly used tools and the newly developed HidroQoL tool. Results: One hundred and eighty-two studies were included in the review. Twenty-two quality of life tools were identified; two or more tools were often used in combination. The most commonly used tools were the Hyperhidrosis Disease Severity Scale, the Dermatology Quality of Life Index and the Hyperhidrosis Quality-of-Life Questionnaire. Patient advisors preferred the new HidroQoL tool, which was considered to be easy to complete and most relevant to hyperhidrosis patients. Conclusions: There are several tools available for assessing quality of life in hyperhidrosis patients; disease specific measures are widely used and appear suitable. It is unclear which tool is the most reliable, although the HidroQoL tool was preferred by a small group of patient advisors.

Management of hyperhidrosis in secondary care

Hyperhidrosis is uncontrollable excessive sweating, which occurs at rest, regardless of temperature. It can have a major impact on peoples quality of life. Primary hyperhidrosis is thought to affect at least 1% of the UK population. There is considerable variation in the availability of treatments in specialist care. This systematic review from the UK assessed the effectiveness of treatments used in specialist care for patients with hyperhidrosis. A comprehensive search was undertaken to find relevant studies of hyperhidrosis treatments. The quality of the studies was assessed. Patient advisors contributed to the interpretation of the results. Fifty studies were included in the review, most were small and of poor quality. The treatments assessed were iontophoresis, botulinum toxin injections, anticholinergic medications, curettage and other technologies that damage the sweat gland. Some studies assessing botulinum toxin injections for hyperhidrosis of the armpit were pooled together to estimate average effects. Our review found that there was moderate quality evidence that botulinum toxin injections reduce symptoms of armpit hyperhidrosis in the short and medium term (up to 16 weeks), compared with placebo (no treatment). There was weak but consistent evidence of some benefit from using iontophoresis for hyperhidrosis of the hands. Evidence for other interventions was of low or very low quality. Overall, the evidence for the effectiveness of treatments for primary hyperhidrosis is limited and few firm conclusions can be drawn. However, there is moderate quality evidence to support the use of botulinum toxin injections in clinical practice. A well conducted, adequately powered, randomised controlled trial of botulinum toxin injections compared with iontophoresis (which is the current standard treatment in many dermatology units for palmar hyperhidrosis, which affects the palms of the hands) for palmar hyperhidrosis may be warranted.

Accuracy of the electronic patient record in a first opinion veterinary practice

The use of electronic patient records (EPRs) in veterinary research is becoming more common place. To date no-one has investigated how accurately and completely they represent the clinical interactions that happen between veterinary professionals, and their clients and patients. The aim of this study was to compare data extracted from consultations within EPRs with data gathered by direct observation of the same consultation. A secondary aim was to establish the inter-rater reliability of two researchers who examined the data extracted from the EPRs. A convenience sample of 36 small animal consultations undertaken by 2 veterinary surgeons (83% by one veterinary surgeon) at a mixed veterinary practice in the United Kingdom was studied. All 36 consultations were observed by a single researcher using a standardised data collection tool. The information recorded in the EPRs was extracted from the Practice Management Software (PMS) systems using a validated XML schema. The XML extracted data was then converted into the same format as the observed data by two independent researchers who examined the extracted information and recorded their findings using the same tool as for the observation. The issues discussed and any action taken relating to those problems recorded in the observed and extracted datasets were then compared. In addition the inter-rater reliability of the two researchers who examined the extracted data was assessed. Only 64.4% of the observed problems discussed during the consultations were recorded in the EPR. The type of problem, who raised the problem and at what point in the consultation the problem was raised significantly affected whether the problem was recorded or not in the EPR. Only 58.3% of observed actions taken during the consultations were recorded in the EPR and the type of action significantly affected whether it would be recorded or not. There was moderate agreement between the two researchers who examined the extracted data. This is the first study that examines how much of the activity that occurs in small animal consultations is recorded in the EPR. Understanding the completeness, reliability and validity of EPRs is vital if they are to continue to be used for clinical research and the results to direct clinical care.

PP028 Hyperhidrosis Quality Of Life Measures: Review And Patient Perspective

Purpose To identify the tools that have been used to measure quality of life in hyperhidrosis research and obtain patient insight on commonly used tools. Methods Twelve databases were searched to identify studies that reported measuring quality of life or described a quality of life tool in the context of hyperhidrosis. Data on the use of the tools were tabulated and hyperhidrosis-specific and dermatology-specific measures were summarised. A workshop was held to obtain the patients’ perspective on the most commonly used tools and the newly developed HidroQoL© tool. Results 182 studies were included in the review. Twenty-two quality of life tools were identified; two or more tools were often used in combination. The most commonly used tools were the Hyperhidrosis Disease Severity Scale, the Dermatology Quality of Life Index and the Hyperhidrosis Quality-of-Life Questionnaire. Patient advisors preferred the new HidroQoL© tool, which was considered to be easy to complete and most relevant to hyperhidrosis patients. Conclusions There are several tools available for assessing quality of life in hyperhidrosis patients; disease specific measures are widely used and appear suitable. It is unclear which tool is the most reliable, although the HidroQoL© tool was preferred by a small group of patient advisors.