Managing Injuries of the Neck Trial (MINT): a randomised controlled trial of treatments for whiplash injuries.

OBJECTIVES: To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs; and to gain participants' perspective on experiencing whiplash injury, NHS treatment, and recovery within the context of the Managing Injuries of the Neck Trial (MINT). DESIGN: Two linked, pragmatic, randomised controlled trials. In Step 1, emergency departments (EDs) were cluster randomised to usual care advice (UCA) or The Whiplash Book advice (WBA)/active management advice. In Step 2, participants were individually randomised to either a single session of advice from a physiotherapist or a physiotherapy package of up to six sessions. An economic evaluation and qualitative study were run in parallel with the trial. SETTING: Twelve NHS trusts in England comprising 15 EDs. PARTICIPANTS: People who attended EDs with an acute whiplash injury of whiplash-associated disorder grades I-III were eligible for Step 1. People who had attended EDs with whiplash injuries and had persistent symptoms 3 weeks after ED attendance were eligible for Step 2. INTERVENTIONS: In Step 1, the control intervention was UCA and the experimental intervention was a psycho-educational intervention (WBA/active management advice). In Step 2 the control treatment was reinforcement of the advice provided in Step 1 and the experimental intervention was a package of up to six physiotherapy treatments. MAIN OUTCOME: The primary outcome was the Neck Disability Index (NDI), which measures severity and frequency of pain and symptoms, and a range of activities including self-care, driving, reading, sleeping and recreation. Secondary outcomes included the mental and physical health-related quality-of-life (HRQoL) subscales of the Short Form questionnaire-12 items (SF-12) and the number of work days lost. RESULTS: A total of 3851 patients were recruited to Step 1 of the trial. 1598 patients attending EDs were randomised to UCA, and 2253 were randomised to WBA/active management. Outcome data were obtained at 12 months for 70% and 80% of participants at Step 1 and Step 2, respectively. The majority of people recovered from the injury. Eighteen per cent of the Step 1 cohort had late whiplash syndrome. There was no statistically or clinically significant difference observed in any of the outcomes for participants attending EDs randomised to UCA or active management advice [difference in NDI 0.5, 95% confidence interval (CI) -1.8 to 2.8]. In Step 2 the physiotherapy package resulted in improvements in neck disability at 4 months compared with a single advice session, but these effects were small at the population level (difference in NDI -3.2, 95% CI -5.8 to -0.7). The physiotherapy package was accompanied by a significant reduction in the number of work days lost at 4-month follow-up (difference -40.2, 95% CI -44.3 to -35.8). CONCLUSIONS: MINT suggests that enhanced psycho-educational interventions in EDs are no more effective than UCA in reducing the burden of acute whiplash injuries. A physiotherapy package provided to people who have persisting symptoms within the first 6 weeks of injury produced additional short-term benefits in neck disability compared with a single physiotherapy advice session. However, from a health-care perspective, the physiotherapy package was not cost-effective at current levels of willingness to pay. Both experimental treatments were associated with increased cost with no discernible gain in health-related quality of life. However, an important benefit of the physiotherapy package was a reduction in work days lost; consequently, the intervention may prove cost-effective at the societal level. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33302125. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 49. See the HTA programme website for further project information.

A multicentred randomised controlled trial of a primary care-based cognitive behavioural programme for low back pain. The Back Skills Training (BeST) trial.

OBJECTIVES: To estimate the clinical effectiveness of active management (AM) in general practice versus AM plus a group-based, professionally led cognitive behavioural approach (CBA) for subacute and chronic low back pain (LBP) and to measure the cost of each strategy over a period of 12 months and estimate cost-effectiveness. DESIGN: Pragmatic multicentred randomised controlled trial with investigator-blinded assessment of outcomes. SETTING: Fifty-six general practices from seven English regions. PARTICIPANTS: People with subacute and chronic LBP who were experiencing symptoms that were at least moderately troublesome. INTERVENTIONS: Participants were randomised (in a ratio of 2:1) to receive either AM+CBA or AM alone. MAIN OUTCOME MEASURES: Primary outcomes were the Roland Morris Disability Questionnaire (RMQ) and the Modified Von Korff Scale (MVK), which measure LBP and disability. Secondary outcomes included mental and physical health-related quality of life (Short Form 12-item health survey), health status, fear avoidance beliefs and pain self-efficacy. Cost-utility of CBA was considered from both the UK NHS perspective and a broader health-care perspective, including both NHS costs and costs of privately purchased goods and services related to LBP. Quality-adjusted life-years (QALYs) were calculated from the five-item EuroQoL. RESULTS: Between April 2005 and April 2007, 701 participants were randomised: 233 to AM and 468 to AM+CBA. Of these, 420 were female. The mean age of participants was 54 years and mean baseline RMQ was 8.7. Outcome data were obtained for 85% of participants at 12 months. Benefits were seen across a range of outcome measures in favour of CBA with no evidence of group or therapist effects. CBA resulted in at least twice as much improvement as AM. Mean additional improvement in the CBA arm was 1.1 [95% confidence interval (CI) 0.4 to 1.7], 1.4 (95% CI 0.7 to 2.1) and 1.3 (95% CI 0.6 to 2.1) change points in the RMQ at 3, 6 and 12 months respectively. Additional improvement in MVK pain was 6.8 (95% CI 3.5 to 10.2), 8.0 (95% CI 4.3 to 11.7) and 7.0 (95% CI 3.2 to 10.7) points, and in MVK disability was 4.3 (95% CI 0.4 to 8.2), 8.1 (95% CI 4.1 to 12.0) and 8.4 (95% CI 4.4 to 12.4) points at 3, 6 and 12 months respectively. At 12 months, 60% of the AM+CBA arm and 31% of the AM arm reported some or complete recovery. Mean cost of attending a CBA course was 187 pounds per participant with an additional benefit in QALYs of 0.099 and an additional cost of 178.06 pounds. Incremental cost-effectiveness ratio was 1786.00 pounds. Probability of CBA being cost-effective reached 90% at about 3000 pounds and remained at that level or above; at a cost-effectiveness threshold of 20,000 pounds the CBA group had an almost 100% probability of being considered cost-effective. User perspectives on the acceptability of group treatments were sought through semi-structured interviews. Most were familiar with key messages of AM; most who had attended any group sessions had retained key messages from the sessions and two-thirds talked about a reduction in fear avoidance and changes in their behaviour. Group sessions appeared to provide reassurance, lessen isolation and enable participants to learn strategies from each other. CONCLUSIONS: Long-term effectiveness and cost-effectiveness of CBA in treating subacute and chronic LBP was shown, making this intervention attractive to patients, clinicians and purchasers. Short-term (3-month) clinical effects were similar to those found in high-quality studies of other therapies and benefits were maintained and increased over the long term (12 months). Cost per QALY was about half that of competing interventions for LBP and because the intervention can be delivered by existing NHS staff following brief training, the back skills training programme could be implemented within the NHS with relative ease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37807450. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study.

OBJECTIVES: To determine whether GPs should advise their older patients with chronic knee pain to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: An equivalence study was designed to compare the effect of advice to use preferentially oral or topical ibuprofen (an NSAID) on knee pain and disability, NSAID-related adverse effects and NHS/societal costs, using a randomised controlled trial (RCT) and a patient preference study (PPS). Reasons for patient preferences for topical or oral preparations, and attitudes to adverse effects, were explored in a qualitative study. SETTING: Twenty-six general practices in the UK. PARTICIPANTS: Participants comprised 585 people with knee pain, aged 50 years or over; 44% were male, mean age 64 years. The RCT had 282 participants: 144 in the oral group and 138 in the topical group. The PPS had 303 participants: 79 in the oral group and 224 in the topical group. INTERVENTIONS: Advice to use preferentially oral or topical NSAIDs for knee pain. OUTCOME MEASURES: The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the Short Form with 36 Items (SF-36), perceived troublesomeness of knee pain, satisfaction with health status, major adverse effects (unplanned hospital admissions and deaths) and minor adverse events over 12 months. The health economic analysis measured the comparative cost per quality-adjusted life-year (QALY) from both an NHS and a societal perspective over 1 and 2 years. RESULTS: Changes in the global WOMAC score at 12-months were equivalent in both studies: topical - oral, RCT difference=2 [95% confidence interval (CI) -2 to 6], PPS difference=1 (95% CI -4 to 6). There were no differences in the secondary outcomes, except for a suggestion, in the RCT, that those in the topical group were more likely to have more severe overall pain and disability as measured by the chronic pain grade, and more likely to report changing treatment because of inadequate pain relief. There were no differences in the rate of major adverse effects but some differences in the number of minor ones. In the RCT, 17% and 10% in the oral and the topical group, respectively, had a defined respiratory adverse effect (95% CI of difference -17% to -2.0%); after 12 months, the change in serum creatinine was 3.7 mmol/l (95% CI 0.9 to 6.5) less favourable in the oral than in the topical group, and 11% of those in the oral group reported changing treatment because of adverse effects compared with 1% in the topical group (p=0.02). None of these differences were seen in the PPS. Oral NSAIDs cost the NHS 191 pounds and 72 pounds more per participant over 1 year in the RCT and PPS respectively. In the RCT the cost per QALY in the oral group, from an NHS perspective, was in the range 9000-12,000 pounds. In the PPS it was 2564 pounds over 1 year, but over 2 years the oral route was more cost-effective. Patient preference for medication type was affected by previous experience of medication (including adverse reactions), other illness, pain elsewhere, anecdotes, convenience, severity of pain and perceived degree of degeneration. Lack of understanding about knee pain and the action of medication led to increased tolerance of symptoms. Potentially important symptoms may inadvertently have been disregarded, increasing participants' risk of suffering a major adverse effect. CONCLUSIONS: Advice to use either oral or topical preparations has an equivalent effect on knee pain, but oral NSAIDs appear to produce more minor adverse effects than topical NSAIDs. Generally, these results support advising older people with knee pain to use topical rather than oral NSAIDS. However, for patients who prefer oral NSAID preparations rather than a topical NSAID, particularly those with more widespread or severe pain, the oral route is a reasonable treatment option, provided that patients are aware of the risks of potentially serious adverse effects from oral medication. Further research is needed into strategies to change prescribing behaviour and ensure that older patients are aware of the potential risks and benefits of using NSAIDs. Observational studies are needed to estimate rates of different predefined minor adverse effects associated with the use of oral NSAIDs in older people as are long-term studies of topical NSAIDs in those for whom oral NSAIDs are not appropriate.

Cost-effectiveness of advising the use of topical or oral ibuprofen for knee pain; the TOIB study [ISRCTN: 79353052].

OBJECTIVE: Advice to use topical or oral NSAIDs is equally effective for the treatment of knee pain in older people. The ingredient cost of topical preparations is typically more than oral preparations, but could save costs because they have fewer adverse effects. A cost-utility study is needed to decide on their comparative cost effectiveness. METHODS: We recruited 585 people aged >or=50 yrs with knee pain; 282 participated in a randomized controlled trial and 303 in a patient preference study from 26 MRC General Practice Research Framework practices in the UK. They received advice to preferentially use topical or oral NSAIDs for knee pain. We calculated the comparative cost per quality-adjusted life year (QALY) from both a National Health Service (NHS) and a societal perspective over 12 and 24 months. RESULTS: Compared with the topical route, oral NSAIDs cost the NHS pound191 and pound72 more over 1 yr in the randomized trial and preference study, respectively. The cost per QALY, from an NHS perspective, was in the range of pound9000- pound12000 in the randomized trial. In the preference study, it was pound2564 over 1 yr, but over 2 yrs the oral route was dominant. CONCLUSIONS: Our cost-effectiveness analysis supports the use of oral NSAIDs in selected patients. Nevertheless, deciding to recommend oral NSAIDs in preference to topical NSAIDs could have a substantial impact on NHS costs because of the uncertainty in the cost-effectiveness estimate.

The cost-effectiveness of testing for hepatitis C in former injecting drug users.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of testing for hepatitis C (HCV) among former injecting drug users (IDUs). DATA SOURCES: Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK mortality data. REVIEW METHODS: A decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people. This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur. A group of epidemiological and clinical experts informed the structure of the model, which has three main components: (1) testing and diagnosis, (2) treatment, and (3) long-term consequences of infection. A fourth component, case-finding strategies, examines the potential impact of case-finding in three settings: prisons, general practice and drug services. RESULTS: Case-finding for HCV is likely to prevent, for 1000 people approached, three cases of decompensated cirrhosis, three deaths due to HCV and one case of hepatocellular cancer (at 30 years). Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding. One liver transplant is likely to be prevented for 10,000 people included in case-finding. Case-finding is likely to cost, in the general case, around pounds sterling 760,000 more than a policy of not case-finding. The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy (the costs of long-term consequences are heavily discounted owing to the duration of the model). Systematically offering testing to 1000 people would cost around pounds sterling 70,000. In terms of life-years gained, case-finding is likely to result in an additional life-year gained for an investment of pounds sterling 20,084. Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as pounds sterling 16,514 per QALY. The probabilistic sensitivity analysis shows that, if NHS policy makers view pounds sterling 30,000 per QALY as an acceptable return on investment, there is a 74% probability that case-finding for HCV would be considered cost-effective. At pounds sterling 20,000 per QALY, the probability that case-finding would be considered cost-effective is 64%. In all analyses, the probability of case-finding being considered cost-effective at a level of pounds sterling 30,000 per QALY was high. Case-finding in drug services is likely to be the most expensive, owing to the high prevalence of cases in the tested population. Correspondingly, benefits are highest for this strategy and cost-effectiveness is similar, in average terms, to the general case. Case-finding in general practice by offering testing to the whole population aged 30-54 years is, paradoxically, estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population. Two approaches to case-finding in prison were considered, based on the results of studies in Dartmoor and the Isle of Wight prisons. These differed substantially in the prevalence of cases identified in the tested populations. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered (pounds sterling 20,000 per QALY). Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-standing and who are consequently at greater risk of progression. In people who were infected more than 20 years previously, case-finding yields benefits at around pounds sterling 15,000 per QALY. Treatment effectiveness was modelled using estimates from randomised controlled trials and lower rates of viral response may be seen in practice. However, estimates of cost-effectiveness remained below pounds sterling 30,000 for all levels of treatment effectiveness above 58% of those shown in the relevant trials. The value of information analysis, based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years, suggests that the maximum value of further research into case-finding is in excess of pounds sterling 19 million. Partial expected value of perfect information (EVPI) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty. This is not surprising, since the point estimates for differences in utility between states and across the arms of the model are small. CONCLUSIONS: Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners. Although there remains considerable uncertainty, it appears unlikely that cost-effectiveness would exceed the levels considered acceptable. Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding. Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced. Further empirical work is required to specify, in practice, different approaches to case-finding in appropriate settings and to evaluate their effectiveness and cost-effectiveness directly.

Early Years Centres for pre-school children with primary language difficulties: what do they cost, and are they cost-effective?

BACKGROUND: High levels of early language difficulties raise practical issues about the efficient and effective means of meeting children's needs. Persistent language difficulties place significant financial pressures on health and education services. This has led to large investment in intervention in the early years; yet, little is known about the actual and relative costs of early years provision. AIMS: To profile the different costs incurred by two Early Years Centres (EYCs) partially funded by the charity I CAN and children receiving what might be termed 'routine' NHS speech therapy to provide an analysis of cost efficiency and equity. METHODS & PROCEDURES: Costings for service provision for 91 children (mean age 2;9) were collected. The activity of staff at each site and the cost of staff allocated to services were computed. Data on other resources were also collected. OUTCOMES & RESULTS: The cost per child per session was on average 12 pounds. Despite the longer course of intervention in the first centre (10 compared with 6 weeks), the cost of the course per child was of the same order (245 pounds compared with 253 pounds). The annual cost of the early years provision per child was higher relative to the costs of the NHS provision, 645 pounds compared with 181 pounds in one EYC (A) and 462 pounds compared with 173 pounds in the other (B). When the cost of standard nursery provision was factored in, the difference in annual costs was rather less, with 5298 pounds for the early years provision (EYC A) relative to 4276 pounds in the comparison group. By contrast, the annual cost of early provision rises to 5926 pounds relative to 8861 pounds in the comparison group (EYC B). CONCLUSIONS: The cost of the EYCs is relatively low and given the positive outcomes reported in the study of which this economic evaluation is a part, there is a good case for saying that they represent an efficient use of resources. The strengths and limitations of the economic evaluation are considered and the need for long-term evaluations is highlighted.

The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.

OBJECTIVES: To estimate the effectiveness and cost-effectiveness of dual-chamber pacemakers versus single-chamber atrial or single-chamber ventricular pacemakers in the treatment of bradycardia due to sick sinus syndrome (SSS) or atrioventricular block (AVB). DATA SOURCES: Electronic databases and relevant Internet sites. Contact with device manufacturers and experts in the field. REVIEW METHODS: A systematic review was carried out of randomised controlled trials (RCTs). The quality of selected studies was appraised using standard frameworks. Meta-analyses, using random effects models, were carried out where appropriate. Limited exploration of heterogeneity was possible. Critical appraisal of economic evaluations was carried out using two frameworks. A decision-analytic model was developed using a Markov approach, to estimate the cost-effectiveness of dual-chamber versus ventricular or atrial pacing over 5 and 10 years as cost per quality-adjusted life-year (QALY). Uncertainty was explored using one-way and probabilistic sensitivity analyses. RESULTS: The searches retrieved a systematic review of effectiveness and cost-effectiveness published in 2002, four parallel group RCTs and 28 cross-over trials. Dual-chamber pacing was associated with lower rates of atrial fibrillation, particularly in SSS, than ventricular pacing, and prevents pacemaker syndrome. Higher rates of atrial fibrillation were seen with dual-chamber pacing than with atrial pacing. Complications occurred more frequently in dual-chamber pacemaker insertion. The cost of a dual-chamber system, over 5 years, including cost of complications and subsequent clinical events in the population, was estimated to be around 7400 pounds. The overall cost difference between single and dual systems is not large over this period: around 700 pounds more for dual-chamber devices. The cost-effectiveness of dual-chamber compared with ventricular pacing was estimated to be around 8500 pounds per QALY in AVB and 9500 pounds in SSS over 5 years, and around 5500 pounds per QALY in both populations over 10 years. Under more conservative assumptions, the cost-effectiveness of dual-chamber pacing is around 30,000 pounds per QALY. The probabilistic sensitivity analysis showed that, under the base-case assumptions, dual-chamber pacing is likely to be considered cost-effective at levels of willingness to pay that are generally considered acceptable by policy makers. In contrast, atrial pacing may be cost-effective compared with dual-chamber pacing. CONCLUSIONS: Dual-chamber pacing results in small but potentially important benefits in populations with SSS and/or AVB compared with ventricular pacemakers. Pacemaker syndrome is a crucial factor in determining cost-effectiveness; however, difficulties in standardising diagnosis and measurement of severity make it difficult to quantify. Dual-chamber pacing is in common usage in the UK. Recipients are more likely to be younger. Insufficient evidence is currently available to inform policy on specific groups who may benefit most from pacing with dual-chamber devices. Further important research is underway. Outstanding research priorities include the economic evaluation of UKPACE studies of the classification, diagnosis and utility associated with pacemaker syndrome and evidence on the effectiveness of pacemakers in children.

The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation.

OBJECTIVES: To consider the effectiveness and cost-effectiveness of pimecrolimus for mild to moderate atopic eczema and tacrolimus for moderate to severe atopic eczema compared with current standard treatment in adults and children. DATA SOURCES: Electronic databases. Experts and the manufacturers of these agents were also approached for information. REVIEW METHODS: The systematic review was carried out using standard methodological guidelines and a stringent quality assessment strategy. A state transition (Markov) model was developed to estimate cost--utility of tacrolimus and pimecrolimus separately, compared with current standard practice with topical corticosteroids, (a) as first-line treatment and (b) as second-line treatment. Pimecrolimus was also compared to emollients only. RESULTS: The pimecrolimus trial reports were of varying quality; however when compared with a placebo (emollient), pimecrolimus was found to be more effective and to provide quality of life improvements. There is very little evidence available about pimecrolimus compared with topical corticosteroids. Compared with a placebo (emollient), both 0.03% and 0.1% tacrolimus were found to be more effective. Compared with a mild corticosteroid, 0.03% tacrolimus is more effective in children as measured by a 90% or better improvement in the Physician's Global Evaluation (PGE). Compared with potent topical corticosteroids, no significant difference in effectiveness is seen with 0.1% tacrolimus as measured by a 75% or greater improvement in the PGE. Minor application site adverse effects are common with tacrolimus. However, this did not lead to increased rates of withdrawal from treatment in trial populations. The PenTag economic model demonstrates a large degree of uncertainty, which was explored in both deterministic and stochastic analyses. This is the case for the cost-effectiveness of pimecrolimus and tacrolimus in first- or second-line use compared with topical steroids. In all cases immunosuppressant regimes were estimated to be more costly than alternatives and differences in benefits to be small and subject to considerable uncertainty. CONCLUSIONS: There is limited evidence from a small number of randomised controlled trials (RCTs) that pimecrolimus is more effective than placebo treatment in controlling mild to moderate atopic eczema. Although greater than for pimecrolimus, the evidence base for tacrolimus in moderate to severe atopic eczema is also limited. At both 0.1% and 0.03% potencies, tacrolimus appears to be more effective than the placebo treatment and mild topical corticosteroids. However, these are not the most clinically relevant comparators. Compared with potent topical corticosteroids, no significant difference was shown. Short-term adverse effects with both immunosuppressants are relatively common, but appear to be mild. Experience of long-term use of the agents is lacking so the risk of rare but serious adverse effects remains unknown. No conclusions can be confidently drawn about the cost-effectiveness of pimecrolimus or tacrolimus compared with active topical corticosteroid comparators. Areas for further research should focus on the effectiveness and safety of the treatments through good-quality RCTs and further economic analysis.

Do the findings of case series studies vary significantly according to methodological characteristics?

OBJECTIVES: To review the use of case series in National Institute for Clinical Excellence (NICE) Health Technology Assessment (HTA) reports, to review systematically the methodological literature for papers relating to the validity of aspects of case series design, and to investigate characteristics and findings of case series using examples from the UK's Health Technology Assessment programme. DATA SOURCES: Electronic databases. NICE website. Reports produced as part of the UK's HTA programme. REVIEW METHODS: NICE HTAs that used information from case series studies were obtained from the NICE website and a range of quality criteria applied. Searches of electronic databases, handsearched journals and the bibliographies of papers were made in order to find studies that assessed aspects of case series design, analysis or quality in relation to study validity. Hypotheses relating to the design of case series studies were developed and empirically investigated using four case examples from existing reports produced as part of the UK's HTA programme (functional endoscopic sinus surgery for nasal polyps, spinal cord stimulation for chronic back pain, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting for chronic angina). Analysis was undertaken comparing studies within each review. RESULTS: There was no consensus on which case series to include in HTAs, how to use them or how to assess their quality, despite them being used in 30% of NICE HTAs. No previous studies empirically investigating methodological characteristics of case series were found. However, it is possible that the search strategy failed to find relevant studies. Poor reporting of case series characteristics severely constrained analysis and there were insufficient data to investigate all the hypotheses. Findings were not consistent across the different topics and were subject to considerable uncertainty. All the examples in our analysis were surgical interventions, which are prone to additional confounding factors due to difficulties of standardisation compared with drug treatment. Our findings may not be generalisable outside the interventions studied. The case series reports included generally exhibited poor reporting of methodological characteristics. This constrained our analysis. The use of several methods of analysis has led to apparently discrepant results. Given the number of analysis performed, the usual level of significance (p = 0.05) should be viewed with caution. The most important limitation of this study is the small number of cases on which the findings are based. The results are therefore tentative and should be viewed with caution. CONCLUSIONS: Case series are incorporated in a significant proportion of health technology assessments. Quality criteria have been used to appraise the quality of case series and decide on their inclusion in reviews of studies using this design. In this small series of case studies drawn from HTAs carried out for the NHS HTA programme, little evidence was found to support the use of many of the factors included in quality assessment tools. Importantly, no relationship was found between study size and outcome across the four examples studied. Isolated examples of a potentially important relationship between other methodological factors and outcome were shown, such as blinding of outcome measurement, but these were not shown consistently across the small number of examples studied. This study is based on a very small sample of studies and should therefore be considered as exploratory. Further investigation of the relationship between methodological features and outcome is justified given the frequency of use of case series in health technology assessments. Further research into the methodological features of case series and their outcome is justified in a wider sample of technologies and larger sets of case series. Value of information analyses including case series could be explored. Further exploration of the differences between case series and randomised controlled trial results, preferably using registry or comprehensive case series data, would be valuable.

The social and vocational outcome of spinal cord injury patients.

Functional status, perception of adjustment, occupational outcome and social functioning were investigated in a group of spinal cord injury (SCI) patients (mean age 34, range 10-74 years) seen at a specialised spinal unit over the period January 1984-December 1988. Functional status was assessed using a standardised scale measuring patients' performance of specific tasks, and other measures of outcome were investigated by a structured interview. Almost two thirds (68%) of the patients were independent according to the standardised scale (33% quadriplegic and 84% paraplegic). Patients' autonomy appeared to be threatened by architectural barriers in and about the house: approximately one third (34%) of those classified as 'independent' on the standardised rehabilitation scale used needed some help in their everyday life. A negative occupational outcome emerged: compared to the pre-morbid situation, 43 patients (44%) were worse off; 48 (49%) did not experience substantial changes--though it must be noted that 68% of these (33/48) were virtually unemployed (ie student, home maker, retired, unemployed) before the injury; and for 6 (7%) some improvement took place. With a multivariate analysis age was the only statistically significant predictor of poor occupational outcome, with older patients being worse off irrespective of the extent of disease and functional autonomy. The paper discusses these results and stresses the need for integrating results based on the use of standardised rehabilitation scales with the analysis of potential barriers influencing a patient's ability to exploit his/her autonomy.