Patient preferences and current practice for adults with steroid-resistant ulcerative colitis: POPSTER mixed-methods study.

BACKGROUND: Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences. OBJECTIVES: The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences. DESIGN: A mixed-methods study, including an online survey, qualitative interviews and discrete choice experiments. SETTING: NHS inflammatory bowel disease services in the UK. PARTICIPANTS: Adults with ulcerative colitis and health-care professionals treating inflammatory bowel disease. RESULTS: We carried out a survey of health-care professionals (n = 168), qualitative interviews with health-care professionals (n = 20) and patients (n = 33), discrete choice experiments with health-care professionals (n = 116) and patients (n = 115), and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals showed that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that anti-tumour necrosis factor drugs (particularly infliximab) are the most frequently offered drugs across most steroid-resistant (and steroid-dependent) patient scenarios, but they are less frequently offered to thiopurine-naive patients. Patient interviews identified several factors influencing their treatment choices, including effectiveness of treatment, recommendations from health-care professionals, route of administration and side effects. Over time, depending on the severity and duration of symptoms and, crucially, as medical treatment options become exhausted, patients are willing to try alternative treatments and, eventually, to undergo surgery. The discrete choice experiments found that the probability of remission and of side effects strongly influences the treatment choices of both patients and health-care professionals. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. The treatments ranked most positively by patients were infliximab and tofacitinib (each preferred by 38% of patients), and the predicted probability of uptake by health-care professionals was greatest for infliximab (62%). LIMITATIONS: The survey and the discrete choice experiments with patients and health-care professionals are limited by their relatively small sample sizes. The qualitative studies are subject to selection bias. The timing of the different substudies, both before and during the COVID-19 pandemic, is a potential limitation. CONCLUSIONS: We have identified factors influencing treatment decisions for steroid-resistant ulcerative colitis and the characteristics to consider when choosing treatments to evaluate in future randomised controlled trials. The findings may be used to improve discussions between patients and health-care professionals when they review treatment options for steroid-resistant ulcerative colitis. FUTURE WORK: This research highlights the need for consensus work to establish an agreed definition of steroid resistance in ulcerative colitis and a greater understanding of the optimal use of tofacitinib and surgery for this patient group. A randomised controlled trial comparing infliximab with tofacitinib is also recommended. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 41. See the NIHR Journals Library website for further project information.

Steroids are one of the main treatments for ulcerative colitis; however, steroids work well for only about 50% of people who take them. There are many other treatments that can be given when steroids do not work, but evidence is limited about how these treatments are best used. To carry out better research about the best treatment options and to improve clinical practice in the future, this study aimed to find out how adults with steroid-resistant ulcerative colitis are managed in hospital and why patients and health-care professionals prefer different treatments. The study combined various methods of research, including an online survey of health-care professionals (n = 168), interviews with health-care professionals (n = 20) and patients (n = 33), a survey of health-care professionals (n = 116) and patients (n = 115) to ask them about treatment preferences, and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals found that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that the most frequently offered drugs are anti-tumour necrosis factor drugs (particularly infliximab). Patient interviews found that several factors influenced treatment choices, including effectiveness of treament, guidance from health-care professionals, route of administration and side effects. Patients were willing to try alternative treatments and surgery over time. The survey found that a higher level of remission and a lower chance of side effects strongly influenced treatment choices. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. Infliximab and tofacitinib were ranked most positively by patients, and the predicted uptake by health-care professionals was greatest for infliximab. The results of this study help improve understanding of why people choose certain treatments, improve decision-making in partnership and inform the design of future research.

Managing the delivery of venous leg ulcer services: A willingness to pay study.

Background and Aims: There is widespread variation in venous leg ulcer (VLU) wound care contributing to inadequate service provision resulting in poor outcomes to patients. Little has been published on the perspectives of where treatments should be carried out. The aim of the study was to quantify respondents' preferences for the preferred place of treatment for VLU. Methods: A UK general population sample was interviewed to elicit preferences for clinic or home care treatment using the willingness to pay elicitation method. Participants were presented with two vignettes describing clinic or home care of VLU, and were asked to select the treatment process that they preferred and provide a detailed explanation for selecting that choice. Then they were asked to state their maximum hypothetical amounts that they were willing to pay for the treatment processes. Results: One hundred fifty-four participants completed the interviews. Respondents were willing to pay £498.96 to receive VLU treatment at a clinic and £505.60 to receive care at home. This difference between the clinic compared to home care was not statistically significant. Advantages of clinic care include being able to book an appointment allowing participants to plan events around the booking and for home care the convenience for those with impaired mobility who may have difficulty traveling. Conclusions: The results show that respondents placed an equal valuation on the place of treatment suggesting no strong preference for either home or clinic care. However, qualitative findings emphasized that impaired mobility may be a barrier to accessing VLU services for some therefore, individuals should be given the choice to select their preferred setting to receive treatment where possible.

Patient preferences for treatment in steroid resistant ulcerative colitis - a discrete-choice experiment.

BACKGROUND AND AIM: Understanding treatment preferences in those patients who are not responding to corticosteroids for ulcerative colitis is important in informing treatment choices. This study aimed to assess the relative importance of treatment characteristics to patients by conducting a discrete-choice experiment. METHODS: Patients completed the questionnaire online. All data were collected between September and December 2020. Participants were shown 13 discrete-choice experiment tasks - a series of side-by-side comparisons of competing, hypothetical treatment characteristics and asked to select a preferred treatment. Survey responses were analysed using descriptive statistics and regression analyses. RESULTS: 115 patients completed the study. Patient preferences were strongest for treatments with a lower chance of side effects, this attribute had the most influence on the choice of treatment patients preferred. The second most important attribute was an improvement in maintaining remission. Conversely, route and frequency of administration were least important on the choice of treatment patients preferred. Respondents were willing to make trade offs and accept treatment benefits to compensate them for receiving a treatment with a less desirable attribute level. Participants were willing to accept a larger benefit of 45% improvement in maintenance of remission to accept a treatment with a higher probability of side effects. The benefit required was smaller with a 10% improvement in remission required to accept a treatment with a lower probability of side effects. CONCLUSION: Quantifying preferences helps to identify and prioritise treatment characteristics that are important to patients. The results highlight the importance of careful discussion of side effects, including the magnitude of risk, using visualisation tools during a patient consultation to support decisions.

The Relationship between Hospital or Surgeon Volume and Outcomes in Lower Limb Vascular Surgery in the United Kingdom and Europe.

BACKGROUND: Peripheral vascular disease is a major cause of death and disability. The extent to which volume influences outcome of lower limb (LL) vascular surgery remains unclear. This review evaluated the relationship between hospital/surgeon volume and outcome in LL surgery. METHODS: Electronic databases-MEDLINE, Embase, the Cochrane Library Databases, Science Citation Index, and CINAHL-proceedings from conferences, citations, and references of included studies were searched. Studies from Europe, of adults undergoing LL vascular surgery reporting outcomes by hospital or surgeon volume were included. The quality of studies was assessed using a modified Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions (Robins1) tool. The association between hospital/surgeon volume and outcome was summarized using tables. RESULTS: Nine studies from different European countries, comprising 67,445 patients who had undergone diverse LL surgeries were included. The increase in hospital/surgeon volume was associated with a decrease in post-operative amputations (hospital at 30 days [odds ratio {OR}: 0.20, 95% confidence interval {CI} 0.29-0.45, P = 0.01; OR: 0.67, 95% CI 0.44-0.9, P = 0.05; OR: 0.96, 95% CI 0.92-1.00, P = 0.06], at 1 year [OR: 0.96, 95% CI 0.93-0.98, P = 0.002; OR: 0.66, 95% CI 0.52-0.84, P < 0.001; OR: 2.05, 95% CI 1.24-3.42, P = 0.01], surgeon at 30 days [OR: 0.53, 95% CI 0.36-0.87, P = 0.01; OR: 0.40, 95% CI 0.18-0.91, P = 0.03; OR: 0.41, 95% CI 0.24-0.69, P = 0.0006]). The evidence on an association between hospital/surgeon volume and mortality was contradictory, but mortality and amputations may covary by hospital volume. There were an insufficient number of studies reporting on the other variables to draw firm conclusions, but their results suggest that high-volume hospitals may undertake more repeated surgeries/revascularizations and limb salvage. The impact of hospital/surgical volume on adverse events and length of hospitalization could not be determined. CONCLUSIONS: High-volume hospitals/surgeons may undertake fewer amputations and mortality and amputations may covary. The finding that hospital and surgeon volume affected the number of secondary amputations has implications on reorganization of vascular surgery services. However, due to the small number and poor quality of some of the included studies, decisions on reorganization of LL vascular surgery services should be supplemented by results from clinical audits. There is need for standardization of definition of volume stratification of outcomes by patient's clinical conditions.

Eliciting Societal Preferences for Weighting QALYs for Burden of Illness and End of Life.

OBJECTIVES: . Recent proposals for value-based assessment, made by the National Institute of Health and Care Excellence (NICE) in the United Kingdom, recommended that burden of illness (BOI) should replace end of life (EOL) as a factor for consideration when deciding on new health technologies. This article reports on a study eliciting societal preferences for 1) BOI from a medical condition, defined as quality-adjusted life year (QALY) loss due to premature mortality and prospective morbidity, and 2) EOL, defined as expected life expectancy of less than 2 years and expected life expectancy gain from new treatment of 3 months or more. METHODS: . A discrete choice experiment survey was conducted with an online UK general population sample. Respondents chose whether they thought the health service should treat patient group A or B: life expectancy and health-related quality of life (HRQOL) with current treatment or life expectancy and HRQOL gains from new treatment, respectively. These attributes were used to derive BOI, QALY gain, and EOL. The respondents' choices were analyzed using conditional logistic regression with a range of specifications examined, including BOI or EOL, QALY gain and QALY gain squared, and robustness. QALY weights were estimated. RESULTS: . The sample of 3669 respondents was representative of the UK population for age and sex. QALY gain had a positive and significant coefficient across all models. QALY gain squared term was negative and significant across all models, indicating a diminishing marginal social value from QALY gains. When included, the BOI coefficient was generally small, positive, and significant, but this was not consistent across the different life expectancy variants. EOL was always positive and significant. CONCLUSIONS: . The social value of a QALY gain is not equal between recipients but depends on whether they are end of life, and it may depend on the prospective burden of illness.

A qualitative study to explore the attitude of clinical staff to the challenges of caring for obese patients.

AIMS AND OBJECTIVES: To examine, from the perspective of staff, if obese patients have any additional care needs, and what the impact of these care requirements are on care provision. We have selected obese patients with venous leg ulceration as an example patient population to explore these questions. BACKGROUND: Anecdotal evidence indicates obesity can increase care requirements and have implications for obesity for care provision. However, little research exists nationally or internationally that provides evidence from a health care perspective. Obesity is a contributory causative factor of lower limb ulceration. In addition to affecting the development of venous leg ulceration, obesity may also impact on the care an obese patient may require and receive. DESIGN: Qualitative study using semi-structured in interviews and framework analysis. METHODS: Interviews were conducted with 18 health care professionals and one focus group with 12 health care professionals who cared for patients with venous ulceration. Data were analysed to identify recurring themes relating to the impact of obesity on care provision. RESULTS: This study found that the increasing numbers of obese patients with leg ulcers are currently presenting challenges to care delivery in many different ways. There was an impact of obesity on patient experience in terms of dignity, safety and quality. Data indicated that neither hospital nor community care services were adequately set up to meet the needs of obese patients in general. CONCLUSION: Health care providers need to recognise that increasing numbers of overweight and obese patients are presenting challenges to care delivery. The study also indicated the need for senior strategic leadership in planning for meeting the needs of obese patients. RELEVANCE TO CLINICAL PRACTICE: Nursing is well placed to provide specialist support to co-ordinate services for obese/oversize patients if a suitable strategic and leadership role is developed. Nurses are used to offering patients help in areas of health promotion such as smoking cessation. Lessons learnt from this area could be applied to help and encourage staff to support patients with weight management.

The random card sort method and respondent certainty in contingent valuation: an exploratory investigation of range bias.

Willingness to pay (WTP) values derived from contingent valuation surveys are prone to a number of biases. Range bias occurs when the range of money values presented to respondents in a payment card affects their stated WTP values. This paper reports the results of an exploratory study whose aim was to investigate whether the effects of range bias can be reduced through the use of an alternative to the standard payment card method, namely, a random card sort method. The results suggest that the random card sort method is prone to range bias but that this bias may be mitigated by restricting the analysis to the WTP values of those respondents who indicate they are 'definitely sure' they would pay their stated WTP.

Putting a value on the avoidance of false positive results when screening for inherited metabolic disease in the newborn.

Despite the increase in the number of inherited metabolic diseases that can be detected at birth using a single dried blood spot sample, the impact of false positive results on parents remains a concern. We used an economic approach - the contingent valuation method - which asks parents to give their maximum willingness to pay for an extension in a screening programme and the degree to which the potential for false positive results diminishes their valuations. 160 parents of a child or children under the age of 16 years were surveyed and given descriptions of the current screening programme in the UK, an extended programme and an extended programme with no false positives. 148 (92.5%) respondents said they would accept the screen for the five extra conditions in an expanded screening programme whilst 10 (6.3%) said they would not and two were unsure. When asked to indicate if they would choose to be screened under an expanded screening programme with no false positive results, 152 (95%) said they would, five (3.1%) said they would not, two were unsure, and there was one non-response. 151 (94.4%) said they preferred the hypothetical test with no false-positives. The mean willingness to pay for the expanded programme was £178 compared to £219 for the hypothetical expanded programme without false positives (p > 0.05). The results suggest that there is widespread parental support for extended screening in the UK and that the number of false-positives is a relatively small issue.

Cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A: results from the botulinum toxin for the upper limb after stroke (BoTULS) trial.

Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY) gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER) of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial: effect on impairment, activity limitation, and pain.

BACKGROUND AND PURPOSE: Botulinum toxin is increasingly used to treat upper limb spasticity due to stroke, but its impact on arm function is unclear. We evaluated botulinum toxin for upper limb spasticity and function poststroke. METHODS: Three hundred thirty-three patients with stroke with upper limb spasticity and reduced arm function participated in a multicenter randomized controlled trial. The intervention group received botulinum toxin type A injection(s) plus a 4-week therapy program. The control group received the therapy program alone. Repeat injection(s) and therapy were available at 3, 6, and 9 months. The primary outcome was upper limb function at 1 month (Action Research Arm Test). Secondary outcomes included measures of impairment, activity limitation, and pain at 1, 3, and 12 months. Outcome assessments were blinded and analysis was by intention to treat. RESULTS: There was no significant difference in achievement of improved arm function (Action Research Arm Test) at 1 month (intervention group: 42 of 167 [25.1%], control group 30 of 154 [19.5%]; P=0.232). Significant differences in favor of the intervention group were seen in muscle tone at 1 month; upper limb strength at 3 months; basic arm functional tasks (hand hygiene, facilitation of dressing) at 1, 3, and 12 months; and pain at 12 months. CONCLUSIONS: Botulinum toxin type A is unlikely to be useful for improving active upper limb function (eg, reaching and grasping) in the majority of patients with spasticity after stroke, but it may improve basic upper limb tasks (hand hygiene, facilitation of dressing) and pain.

The social value of a QALY: raising the bar or barring the raise?

BACKGROUND: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England, there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were released during a time of considerable debate about the NICE threshold, and authors with differing perspectives have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for those who conducted the research to contribute to the debate as to its implications for NICE. DISCUSSION: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents' answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the other that greater weight could be given to QALYs gained by some groups. SUMMARY: Although we conducted only a feasibility study and a modelling exercise, neither present compelling evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be moved up for some types of QALY and down for others. While many members of the public appear to be open to the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have any secure evidence base for introducing such a system.

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A.

BACKGROUND: Following a stroke, 55-75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear.The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. TRIAL DESIGN: A multi-centre open label parallel group randomised controlled trial and economic evaluation. PARTICIPANTS: Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. INTERVENTIONS: Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). OUTCOMES: Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. PARTICIPANTS are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy.Randomisation : A web based central independent randomisation service. Blinding: Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. SAMPLE SIZE: 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0-3 and 6 points for those with ARAT of 4-56. TRIAL REGISTRATION: ISRCTN78533119 Eudra CT 2004-002427-40 CTA 17136/0230/001 FUNDING: National Institute for Health Research, Health Technology Assessment Programme. Ipsen Ltd provide botulinum toxin type A (Dysport(R)).

The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.

BACKGROUND: Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. INTERPRETATION: Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.

The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.

BACKGROUND: Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1.57 [95% CI 1.19-2.08]), but there was no significant difference between valproate and lamotrigine (1.25 [0.94-1.68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55 [1.07-2.24] and topiramate (1.89 [1.32-2.70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76 [0.62-0.94]), and for the subgroup with an idiopathic generalised epilepsy 0.68 (0.53-0.89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy. INTERPRETATION: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

Preferences for access to the GP: a discrete choice experiment.

BACKGROUND: Access to primary care services is one of the key components of the NHS Plan which states that patients should be able to see a health professional within 24 hours and a GP within 48 hours. However, it is not clear how patients value speed of access in comparison with other aspects of primary care. AIM: To investigate patient preferences when making an routine appointment for a GP, and to describe the trade-offs and relationships between speed of access, choice of time and choice of doctor in different patient groups. DESIGN OF STUDY: Discrete choice experiment. SETTING: Adults consulting a GP in six general practices in Sunderland. METHOD: Choice sets based on three attributes (time to appointment, choice of time, choice of doctor) were presented in a self-completion questionnaire. RESULTS: We obtained 6985 observations from 1153 patients. We found that the waiting time to make an appointment was only important if the appointment is for a child or when attending for a new health problem. Other responders would trade-off a shorter waiting time and be willing to wait in order to either see their own choice of doctor or attend an appointment at their own choice of time. For responders who work, choice of time is six times more important than a shorter waiting time and they are willing to wait up to 1 day extra for this. Those with a long-standing illness value seeing their own GP more than seven times as much as having a shorter waiting time for an appointment and will wait an extra 1 day for an appointment with the GP of their choice, women will wait an extra 2 days, and older patients an extra 2.5 days. CONCLUSION: Speed of access is of limited importance to patients accessing their GP, and for many is outweighed by choice of GP or convenience of appointment.

Implicit versus explicit ranking: on inferring ordinal preferences for health care programmes based on differences in willingness-to-pay.

The paper explores the merit of the willingness-to-pay (WTP) method as a way to elicit public preferences regarding health care priorities. The aim is to test the extent to which the implicit ranking inferred from the ordinal differences in WTP-values corresponds with respondents' explicit ranking of the same programmes. This issue of convergent validity is explored by face-to-face interviewing of population samples in six European countries-in total 1240 respondents. The most consistent result is the inconsistency of WTP and explicit ranking in all six countries. The convergent validity of WTP is low, particularly among those who did not state different WTP-values on the three programmes being considered.

Willingness to pay for public health care: a comparison of two approaches.

When applying willingness-to-pay (WTP) in economic evaluations, there have been strong theoretical arguments for the use of ex ante insurance-based questions, which can be framed either as insurance premiums or taxation contributions. This paper suggests theoretical reasons why respondents may value a programme differently in these two different ex ante approaches, and inquires empirically into the potential existence of such differences. A split-sample interview study was undertaken in Denmark. The proportion of respondents willing to pay is higher in the community version, and the respondents use different reasons for being and not being willing to pay.

The impact of information on non-health attributes on willingness to pay for multiple health care programmes.

Despite the acceptance that health gain is the most important attribute of health care, other aspects of health care may affect utility. The aim of this paper is to report an experiment to test the impact of providing different levels of information in the context of the EuroWill study, a joint contingent valuation (CV) of multiple health programmes. Three hundred and three respondents were simultaneously asked for their willingness-to-pay (WTP) for three health care programmes: more heart operations, a new breast cancer treatment and a helicopter ambulance service. To test for the impact of variation in information, three versions of one of the programmes (heart) were provided. Results show that WTP for all three programmes tended to be significantly higher for respondents who were provided additional positive information about the heart programme. Our results show that CV of health care programmes, which only take into account medical outcomes, may lead to the value of such programmes not being adequately estimated, and that the impact of information may even be more decisive in the context of joint evaluation of multiple, rather than single, programmes.

The use of willingness to pay to assess public preferences towards the fortification of foodstuffs with folic acid.

OBJECTIVES: To assess public attitudes towards the fortification of flour with folic acid, and quantify their intensity of preference towards the proposed policy. DESIGN: Structured interviews describing the proposed policy of fortification followed by questions about the respondent's preferences towards fortification. SETTING AND PARTICIPANTS: A United Kingdom community sample of 76 people interviewed at home. MAIN VARIABLES STUDIED: Direction of preference towards fortification, willingness to pay (WTP) for the preferred course of action, and the reasons behind their preferences. RESULTS: Responses showed that 51 (67%) were in favour of fortification, 15 (20%) were opposed, while the remaining 10 (13%) were either indifferent or were unsure. Those in favour of fortification tended to be younger and poorer than those opposed to it. Willingness to pay estimates show that those in favour of food fortification had more intense preferences, with mean and median WTP around twice as great. Reasons for being willing to pay were centred on the health benefits, with particular reference being made to the intervention saving lives and it being preventative. Those opposed tended to believe that there was insufficient evidence. CONCLUSIONS: The combination of a policy vote, WTP and qualitative data, allow us to assess the direction, intensity and motivations behind people's preferences. Further work needs to be undertaken to gather more robust estimates of public preferences for fortification, and to better understand attitudes towards public health interventions more generally.