ABSTRACT: BackgroundA range of new therapeutic agents are now available for the management of Alzheimer's disease. With limited resources available
however, policy-makers and other health care professionals have to prioritise and judge competing treatments on criteria such
as the magnitude of clinical effectiveness and cost-effectiveness. Policy guidance that restricts treatments to defined patient
sub-groups can improve the cost-effectiveness of treatments, and can help limit rises in health care expenditures. Budget
impact models that estimate the amount of additional costs and potential savings are being increasingly used by policy-makers.
However, the amount of savings estimated in such models depends on the effectiveness of treatment in changing morbidity, and
the association between morbidity and costs.
AimTo examine the magnitude of cost savings arising from provision of treatment to different patient sub-groups, using policy
guidance decisions made by the National Institute for Health and Clinical Excellence (NICE) for cholinesterase inhibitor therapies
in Alzheimer's Disease (AD) in the United Kingdom National Health Service (NHS).
MethodCohort simulation modelling.
ResultsPolicy guidance decisions that restricted treatment to smaller patient sub-groups were associated with lower overall care
costs, but did not reduce drug costs.
ConclusionsGiven increasing recognition by health policy-makers of the importance of affordability of new treatments, greater attention
should be paid to measurement of cost impacts by sub-groups within health economic modelling.
Key wordsAlzheimer's disease-costs-cost analysis-dementia-economics-sub-groups-budget impact-donepezil-cholinesterase inhibitor therapies
The Journal of Nutrition Health and Aging 04/2012; 14(8):664-668. · 2.69 Impact Factor
ABSTRACT: To investigate the clinical effectiveness and cost-effectiveness of laxatives versus dietary and lifestyle advice, and standardised versus personalised dietary and lifestyle advice.
A prospective, pragmatic, three-armed cluster randomised trial with an economic evaluation.
General practices in England and Scotland, UK.
People aged ≥ 55 years with chronic constipation, living in private households. Participants were identified as those who had been prescribed laxatives three or more times in the previous 12 months, or with a recorded diagnosis of chronic functional constipation.
Prescription of laxatives, with class of laxative and dose at the discretion of the GP and patient (standard care control arm); standardised, non-personalised dietary and lifestyle advice; and, personalised dietary and lifestyle advice, with reinforcement.
The primary outcome was the constipation-specific Patient Assessment of Constipation-Symptoms (PAC-SYM)/Patient Assessment of Constipation-Quality of Life (PAC-QOL).
The trial planned to recruit and retain 1425 patients from 57 practices (19 per arm); however, only 154 patients were recruited from 19 practices. Due to these low recruitment rates it was not possible to report the conventional trial findings. Baseline characteristics of the sample from data gathered from both postal self-completion questionnaires and face-to-face interviews suggest that our sample experienced very few symptoms of constipation (PAC-SYM) and that the condition itself did not have a major impact upon their quality of life (PAC-QOL). The low level of symptoms of constipation is most likely explained by 90% of the sample using a laxative in the previous week. Most participants in our sample were satisfied with the performance of their laxatives, and levels of anxiety and depression were low. Their fibre consumption was classified as 'moderate' but their average water consumption fell below the recommended guidelines. Daily diaries, completed each day for a period of 6 months, were analysed primarily in terms of overall response rate and item response rates, and the participants accepted this method of data collection. For the economic evaluation, all of the trial arms experienced a reduction in utility, as measured by EQ-5D. There was no statistical evidence to suggest that either the personalised intervention arm or the standardised intervention arm was associated with significant changes in utility at 3 months compared with the control arm. Data on related health-care costs show a cost saving of £13.34 for those in the personalised arm, compared with the control arm, and a smaller cost saving for the standardised arm. These savings primarily occurred because of reduced hospital costs. There was no significant change measured in utility, so the personalised arm appeared to be the preferred course, producing the greatest cost savings.
Due to the low number of participants in the trial, no firm conclusions could be drawn about the effectiveness of the interventions. However, a number of factors that contributed to the conduct and progress of the trial are highlighted, which may be relevant to others conducting research on a similar topic or population.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 14, No. 52. See the HTA programme website for further project information.
Health technology assessment (Winchester, England). 11/2010; 14(52):1-251.
ABSTRACT: To examine the clinical effectiveness and cost-effectiveness of tonsillectomy/adeno-tonsillectomy in children aged 4-15 years with recurrent sore throats in comparison with standard non-surgical management.
A pragmatic randomised controlled trial with economic analysis comparing surgical intervention with conventional medical treatment in children with recurrent sore throats (trial) and a parallel non-randomised cohort study (cohort study).
Five secondary care otolaryngology departments located in the north of England or west of Scotland.
268 (trial: 131 allocated to surgical management; 137 allocated to medical management) and 461 (cohort study: 387 elected to have surgical management; 74 elected to have medical management) children aged between 4 and 15 years on their last birthday with recurrent sore throats. Participants were stratified by age (4-7 years, 8-11 years, 12-15 years).
Treatment was tonsillectomy and adeno-tonsillectomy with adenoid curettage and tonsillectomy by dissection or bipolar diathermy according to surgical preference within 12 weeks of randomisation. The control was non-surgical conventional medical treatment only.
The primary clinical outcome was the reported number of episodes of sore throat in the 2 years after entry into the study. Secondary clinical outcomes included: the reported number of episodes of sore throat; number of sore throat-related GP consultations; reported number of symptom-free days; reported severity of sore throats; and surgical and anaesthetic morbidity. In addition to the measurement of these clinical outcomes, the impact of the treatment on costs and quality of life was assessed.
Of the 1546 children assessed for eligibility, 817 were excluded (531 not meeting inclusion criteria, 286 refused) and 729 enrolled to the trial (268) or cohort study (461). The mean (standard deviation) episode of sore throats per month was in year 1 - cohort medical 0.59 (0.44), cohort surgical 0.71 (0.50), trial medical 0.64 (0.49), trial surgical 0.50 (0.43); and in year 2 - cohort medical 0.38 (0.34), cohort surgical 0.19 (0.36), trial medical 0.33 (0.43), trial surgical 0.13 (0.21). During both years of follow-up, children randomised to surgical management were less likely to record episodes of sore throat than those randomised to medical management; the incidence rate ratios in years 1 and 2 were 0.70 [95% confidence interval (CI) 0.61 to 0.80] and 0.54 (95% CI 0.42 to 0.70) respectively. The incremental cost-effectiveness ratio was estimated as 261 pounds per sore throat avoided (95% confidence interval 161 pounds to 586 pounds). Parents were willing to pay for the successful treatment of their child's recurrent sore throat (mean 8059 pounds). The estimated incremental cost per quality-adjusted life-year (QALY) ranged from 3129 pounds to 6904 pounds per QALY gained.
Children and parents exhibited strong preferences for the surgical management of recurrent sore throats. The health of all children with recurrent sore throat improves over time, but trial participants randomised to surgical management tended to experience better outcomes than those randomised to medical management. The limitations of the study due to poor response at follow-up support the continuing careful use of 'watchful waiting' and medical management in both primary and secondary care in line with current clinical guidelines until clear-cut evidence of clinical effectiveness and cost-effectiveness is available.
Current Controlled Trials ISRCTN47891548.
Health technology assessment (Winchester, England). 03/2010; 14(13):1-164, iii-iv.
ABSTRACT: A range of new therapeutic agents are now available for the management of Alzheimer's disease. With limited resources available however, policy-makers and other health care professionals have to prioritise and judge competing treatments on criteria such as the magnitude of clinical effectiveness and cost-effectiveness. Policy guidance that restricts treatments to defined patient sub-groups can improve the cost-effectiveness of treatments, and can help limit rises in health care expenditures. Budget impact models that estimate the amount of additional costs and potential savings are being increasingly used by policy-makers. However, the amount of savings estimated in such models depends on the effectiveness of treatment in changing morbidity, and the association between morbidity and costs.
To examine the magnitude of cost savings arising from provision of treatment to different patient sub-groups, using policy guidance decisions made by the National Institute for Health and Clinical Excellence (NICE) for cholinesterase inhibitor therapies in Alzheimer's Disease (AD) in the United Kingdom National Health Service (NHS).
Cohort simulation modelling.
Policy guidance decisions that restricted treatment to smaller patient sub-groups were associated with lower overall care costs, but did not reduce drug costs.
Given increasing recognition by health policy-makers of the importance of affordability of new treatments, greater attention should be paid to measurement of cost impacts by sub-groups within health economic modelling.
The Journal of Nutrition Health and Aging 01/2010; 14(8):664-8. · 2.69 Impact Factor
ABSTRACT: To test the hypotheses that older people and their informal carers are not disadvantaged by home-based rehabilitation (HBR) relative to day hospital rehabilitation (DHR) and that HBR is less costly.
Two-arm randomised controlled trial.
Four trusts in England providing both HBR and DHR.
Clinical staff reviewed consecutive referrals to identify subjects who were potentially suitable for randomisation according to the defined inclusion criteria.
Patients were randomised to receive either HBR or DHR.
The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) scale. Secondary outcome measures included the EuroQol 5 dimensions (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Therapy Outcome Measures (TOMs), hospital admissions and the General Health Questionnaire (GHQ-30) for carers.
Overall, 89 subjects were randomised and 42 received rehabilitation in each arm of the trial. At the primary end point of 6 months there were 32 and 33 patients in the HBR and DHR arms respectively. Estimated mean scores on the NEADL scale at 6 months, after adjustment for baseline, were not significantly in favour of either HBR or DHR [DHR 30.78 (SD 15.01), HBR 32.11 (SD 16.89), p = 0.37; mean difference -2.139 (95% CI -6.870 to 2.592)]. Analysis of the non-inferiority of HBR over DHR using a 'non-inferiority' limit (10%) applied to the confidence interval estimates for the different outcome measures at 6 months' follow-up demonstrated non-inferiority for the NEADL scale, EQ-5D and HADS anxiety scale and some advantage for HBR on the HADS depression scale, of borderline statistical significance. Similar results were seen at 3 and 12 months' follow-up, with a statistically significant difference in the mean EQ-5D(index) score in favour of DHR at 3 months (p = 0.047). At the end of rehabilitation, a greater proportion of the DHR group showed a positive direction of change from their initial assessment with respect to therapist-rated clinical outcomes; however, a lower proportion of HBR patients showed a negative direction of change and, overall, median scores on the TOMs scales did not differ between the two groups. Fewer patients in the HBR group were admitted to hospital on any occasion over the 12-month observation period [18 (43%) versus 22 (52%)]; however, this difference was not statistically significant. The psychological well-being of patients' carers, measured at 3, 6 and 12 months, was unaffected by whether rehabilitation took place at day hospital or at home. As the primary outcome measure and EQ-5D(index) scores at 6 months showed no significant differences between the two arms of the trial, a cost-minimisation analysis was undertaken. Neither the public costs nor the total costs at the 6-month follow-up point (an average of 213 days' total follow-up) or the 12-month follow-up point (an average of 395 days' total follow-up) were significantly different between the groups.
Compared with DHR, providing rehabilitation in patients' own homes confers no particular disadvantage for patients and carers. The cost of providing HBR does not appear to be significantly different from that of providing DHR. Rehabilitation providers and purchasers need to consider the place of care in the light of local needs, to provide the benefits of both kinds of services. Caution is required when interpreting the results of the RCT because a large proportion of potentially eligible subjects were not recruited to the trial, the required sample size was not achieved and there was a relatively large loss to follow-up.
Current Controlled Trials ISRCTN71801032.
Health technology assessment (Winchester, England). 09/2009; 13(39):1-143, iii-iv.
ABSTRACT: To investigate the clinical effectiveness and cost-effectiveness of bulk-forming, stimulant and osmotic laxatives, and also of adding a second type of laxative agent in the treatment of patients whose constipation is not resolved by a single agent. Additionally, to define the meaning of constipation in older people from the perspective of GPs and older patients, and to investigate the use of prescribed and non-prescribed treatments for constipation in older people together with their adherence to prescribed treatments.
A multicentre pragmatic, factorial randomised controlled trial with economic evaluation and qualitative study using in-depth interviews and focus groups with older people, GPs and community nurses.
General practices in north-east England.
People aged 55 years or over with chronic constipation living in private households.
Six stepped-treatment strategies using three classes of laxatives: bulk, stimulant and osmotic preparations, singly and in combination.
The primary outcome was the constipation-specific Patient Assessment of Constipation--Symptoms/Patient Assessment of Constipation--Quality of Life. Secondary outcomes included EuroQoL 5 Dimensions, reported number of bowel movements per week, the presence/absence of the other Rome II criteria for constipation, adverse effects of treatment and relapse rates.
Recruitment to the trial was difficult and the trial was closed after recruiting 19 participants. GP participants provided patient-centred definitions that focused on the idea of a change from the norm as defined by the individual patient and 'textbook definitions' that focused on reduced frequency of defecation associated with a range of unpleasant sensations and other clinical symptoms. Nurses' definitions of constipation included both a patient-centred perspective and the description of particular symptoms associated with constipation. Older participants defined constipation in terms of frequency of bowel movements and changes in normal bowel routine. Older participants perceived constipation as follows: linked to specific diseases, medical conditions or health problems; caused by the consumption of specific medications or surgical procedures; caused by diet or eating habits; part of the ageing process; due to not going to the toilet when having the urge to defecate; hereditary; caused by stress or worry; and caused by environmental exposure. GP participants suggested that constipation is due to changes in diet and lifestyle; the physiology and degenerative processes of ageing; and the iatrogenic impact of opiate medications. Nurse participants identified that constipation is linked to decreased mobility, decreased food intake, decreased fluid intake and consumption of certain medications. For many older people their constipation emerged as a problem over a period of time; for some the 'condition' had existed for many years. Self-management of constipation had typically been their first response to the symptoms and continued once professional help had been sought. Older participants had a wide experience of different management strategies and treatments for constipation, and at the time of the study had firm preferences about the laxatives they would use. GP participants recognised the experience and use of laxatives of their patients. They exhibited strong personal preferences for different laxatives, often prescribing them in combination. Nurses were more likely than GPs to treat and prevent constipation using non-laxative measures; these included providing advice on appropriate dietary changes, increasing fluid intake and, if possible, encouraging exercise and mobility.
There is little shared understanding between patients and professionals about 'normal' bowel function with little consensus in general practice of the optimum management strategies for chronic constipation and the most effective strategies to use. Chronic constipation is seen as less important than other conditions prevalent in general practice (e.g. diabetes) because it is not an agreed management target within national frameworks. Consequently, practitioners had little interest in constipation as a research topic. Patient preferences and the absence of patient equipoise formed an enormous barrier to the recruitment of patients in the implementation of this trial. Studies are needed to investigate different methods of recruitment within the constraints of current ethical guidelines on 'opting in' and to identify barriers and facilitators to recruitment to complex trials in general. Patient preference trials and natural cohort observational studies are also needed to investigate the effectiveness or cost-effectiveness of different laxatives and treatment strategies in the management of chronic constipation.
Health technology assessment (Winchester, England) 06/2008; 12(13):iii-iv, ix-139. · 4.26 Impact Factor
ABSTRACT: To compare clinicians' choice of one of the standard epilepsy drug treatments (carbamazepine or valproate) versus appropriate comparator new drugs.
A clinical trial comprising two arms, one comparing new drugs in carbamazepine and the other with valproate.
A multicentre study recruiting patients with epilepsy from hospital outpatient clinics.
Patients with an adequately documented history of two or more clinically definite unprovoked epileptic seizures within the last year for whom treatment with a single antiepileptic drug represented the best therapeutic option.
Arm A was carbamazepine (CBZ) versus gabapentin (GBP) versus lamotrigine (LTG) versus oxcarbazepine (OXC) versus topiramate (TPM). Arm B valproate (VPS) versus LTG versus TPM.
Time to treatment failure (withdrawal of the randomised drug for reasons of unacceptable adverse events or inadequate seizure control or a combination of the two) and time to achieve a 12-month remission of seizures. Time from randomisation to first seizure, 24-month remission of seizures, incidence of clinically important adverse events, quality of life (QoL) outcomes and health economic outcomes were also considered.
Arm A recruited 1721 patients (88% with symptomatic or cryptogenic partial epilepsy and 10% with unclassified epilepsy). Arm B recruited 716 patients (63% with idiopathic generalised epilepsy and 25% with unclassified epilepsy). In Arm A LTG had the lowest incidence of treatment failure and was statistically superior to all drugs for this outcome with the exception of OXC. Some 12% and 8% fewer patients experienced treatment failure on LTG than CBZ, the standard drug, at 1 and 2 years after randomisation, respectively. The superiority of LTG over CBZ was due to its better tolerability but there is satisfactory evidence indicating that LTG is not clinically inferior to CBZ for measures of its efficacy. No consistent differences in QoL outcomes were found between treatment groups. Health economic analysis supported LTG being preferred to CBZ for both cost per seizure avoided and cost per quality-adjusted life-year gained. In Arm B for time to treatment failure, VPS, the standard drug, was preferred to both TPM and LTG, as it was the drug least likely to be associated with treatment failure for inadequate seizure control and was the preferred drug for time to achieving a 12-month remission. QoL assessments did not show any between-treatment differences. The health economic assessment supported the conclusion that VPS should remain the drug of first choice for idiopathic generalised or unclassified epilepsy, although there is a suggestion that TPM is a cost-effective alternative to VPS.
The evidence suggests that LTG may be a clinical and cost-effective alternative to the existing standard drug treatment, CBZ, for patients diagnosed as having partial seizures. For patients with idiopathic generalised epilepsy or difficult to classify epilepsy, VPS remains the clinically most effective drug, although TPM may be a cost-effective alternative for some patients. Three new antiepileptic drugs have recently been licensed in the UK for the treatment of epilepsy (levetiracetam, zonisamide and pregabalin), therefore these drugs should be compared in a similarly designed trial.
Health technology assessment (Winchester, England) 11/2007; 11(37):iii-iv, ix-x, 1-134. · 4.26 Impact Factor
ABSTRACT: Wandering occurs in 15-60% of people with dementia. Psychosocial interventions rather than pharmacological methods are recommended, but evidence for their effectiveness is limited and there are ethical concerns associated with some non-pharmacological approaches, such as electronic tracking devices.
To determine the clinical and cost effectiveness and acceptability of non-pharmacological interventions to reduce wandering in dementia.
A systematic review to evaluate effectiveness of the interventions and to assess acceptability and ethical issues associated with their use. The search and review strategy, data extraction and analysis followed recommended guidance. Papers of relevance to effectiveness, acceptability and ethical issues were sought.
(i) Clinical effectiveness. Eleven studies, including eight randomised controlled trials, of a variety of interventions, met the inclusion criteria. There was no robust evidence to recommend any intervention, although there was some weak evidence for exercise. No relevant studies to determine cost effectiveness met the inclusion criteria. (ii) Acceptability/ethical issues. None of the acceptability papers reported directly the views of people with dementia. Exercise and music therapy were the most acceptable interventions and raised no ethical concerns. Tracking and tagging devices were acceptable to carers but generated considerable ethical debate. Physical restraints were considered unacceptable.
In order to reduce unsafe wandering high quality research is needed to determine the effectiveness of non-pharmacological interventions that are practically and ethically acceptable to users. It is important to establish the views of people with dementia on the acceptability of such interventions prior to evaluating their effectiveness through complex randomised controlled trials.
International Journal of Geriatric Psychiatry 02/2007; 22(1):9-22. · 2.42 Impact Factor
ABSTRACT: To determine the effectiveness and cost-effectiveness of non-pharmacological interventions (excluding subjective barriers) in the prevention of wandering in people with dementia, in comparison with usual care, and to evaluate through the review and a qualitative study the acceptability to stakeholders of such interventions and identify ethical issues associated with their use.
Major electronic databases were searched up until 31 March 2005. Specialists in the field.
Selected studies were assessed and analysed. The results of two of the efficacy studies that used similar interventions, designs and outcome measures were pooled in a meta-analysis; results for other studies which reported standard deviations were presented in a forest plot. Owing to a lack of cost-effectiveness data, a modelling exercise could not be performed. Four focus groups were carried out with relevant stakeholders (n = 19) including people with dementia and formal and lay carers to explore ethical and acceptability issues in greater depth. Transcripts were coded independently by two reviewers to develop a coding frame. Analysis was via a thematic framework approach.
Ten studies met the inclusion criteria (multi-sensory environment, three; music therapy, one; exercise, one; special care units, two; aromatherapy, two; behavioural intervention, one). There was no robust evidence to recommend any non-pharmacological intervention to reduce wandering in dementia. There was some evidence, albeit of poor quality, for the effectiveness of exercise and multi-sensory environment. There were no relevant studies to determine the cost-effectiveness of the interventions. Findings from the narrative review and focus groups on acceptability and ethical issues were comparable. Exercise and distraction therapies were the most acceptable interventions and raised no ethical concerns. All other interventions were considered acceptable except for physical restraints, which were considered unacceptable. Considerable ethical concerns exist with the use of electronic tagging and tracking devices and physical barriers. Existing literature ignores the perspectives of people with dementia. The small number of participants with dementia expressed caution regarding the use of unfamiliar technology. Balancing risk and risk assessment was an important theme for all carers in the management of wandering.
There is no robust evidence so far to recommend the use of any non-pharmacological intervention to reduce or prevent wandering in people with dementia. High-quality studies, preferably randomised controlled trials, are needed to determine the clinical and cost-effectiveness of non-pharmacological interventions that allow safe wandering and are considered practically and ethically acceptable by carers and people with dementia. Large-scale, long-term cohort studies are needed to evaluate the morbidity and mortality associated with wandering in dementia for people both in the community and in residential care. Such data would inform future long-term cost-effectiveness studies.
Health technology assessment (Winchester, England) 09/2006; 10(26):iii, ix-108. · 4.26 Impact Factor