Health technology assessment : HTA
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Health Technol Assess · Mar 2006
ReviewSurveillance of Barrett's oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling.
To assess what is known about the effectiveness, safety, affordability, cost-effectiveness and organisational impact of endoscopic surveillance in preventing morbidity and mortality from adenocarcinoma in patients with Barrett's oesophagus. In addition, to identify important areas of uncertainty in current knowledge for these programmes and to identify areas for further research. ⋯ The systematic review concludes that there is insufficient evidence available to assess the clinical effectiveness of surveillance programmes of Barrett's oesophagus. There are numerous gaps in the evidence, of which the lack of RCT data is the major one. The expert workshop reflected these gaps in the range of topics raised as important in answering the question of the effectiveness of surveillance. Previous models of cost-effectiveness have most recently shown that surveillance programmes either do more harm than good compared with no surveillance or are unlikely to be cost-effective at usual levels of willingness to pay. Our cost--utility model has shown that, across a range of values for the various parameters that have been chosen to reflect uncertainty in the inputs, it is likely that surveillance programmes do more harm than good -- costing more and conferring lower quality of life than no surveillance. Probabilistic analysis shows that, in most cases, surveillance does more harm and costs more than no surveillance. It is unlikely, but still possible, that surveillance may prove to be cost-effective. The cost-effectiveness acceptability curve, however, shows that surveillance is unlikely to be cost-effective at either the 'usual' level of willingness to pay ( pound 20,000-30,000 per QALY) or at much higher levels. The expected value of perfect information at the population level is pound 6.5 million. Future research should target both the overall effectiveness of surveillance and the individual elements that contribute to a surveillance programme, particularly the performance of the test and the effectiveness of treatment for both Barrett's oesophagus and ACO. In addition, of particular importance is the clarification of the natural history of Barrett's oesophagus.
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Health Technol Assess · Mar 2006
ReviewThe clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review.
To examine the clinical effectiveness and cost-effectiveness of newer antiepileptic drugs (AEDs) for epilepsy in children: gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate and vigabatrin. ⋯ The prognosis for children diagnosed with epilepsy is generally good, with a large proportion responding well to the first treatment given. A substantial proportion, however, will not respond well to treatment, and for these patients the clinical goal is to find an optimal balance between the benefits and side-effects of any treatment given. For the newly, or recently, diagnosed population, the key question for the newer drugs is how soon they should be tried. The cost-effectiveness of using these agents early, in place of one of the older agents, will depend on the effectiveness and tolerability of these agents compared with the older agents; the evidence from the available trial data so far suggests that the newer agents are no more effective but may be somewhat better tolerated than the older agents, and so the cost-effectiveness for early use will depend on the trade-off between effectiveness and tolerability, both in terms of overall (long-term) treatment retention and overall utility associated with effects on seizure rate and side-effects. There are insufficient data available to estimate accurately the nature of this trade off either in terms of long-term treatment retention or utility. Better information is required from RCTs before any rational evidence-based prescribing strategy could be developed. Ideally, RCTs should be conducted from a 'public health' perspective, making relevant comparisons and incorporating outcomes of interest to clinicians and patients, with sufficiently long-term follow-up to determine reliably the clinical utility of different treatments, particularly with respect to treatment retention and the balance between effectiveness and tolerability. RCTs should mirror clinical practice with respect to diagnosis, focusing on defined syndromes or, where no syndrome is identified, on groups defined by specific seizure type(s) and aetiology. Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options and outcomes. Diagnosis-specific decision-analytic models are required; further research may be required to inform parameter values adequately with respect to epidemiology and clinical practice.
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Health Technol Assess · Mar 2006
ReviewTopotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.
To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer. ⋯ For participants with platinum-resistant disease there was a low probability of response to treatment with PLDH, topotecan or paclitaxel. Furthermore, there was little difference between the three comparators in relation to overall survival. The comparators did, however, differ considerably in their toxicity profiles. Given the low survival times and response rates, it appears that the maintenance of quality of life and the control of symptoms and toxicity are paramount in this patient group. As the three comparators differed significantly in terms of their toxicity profiles, patient and physician choice is also an important element that should be addressed when decisions are made regarding second-line therapy. It can also be suggested that this group of patients may benefit from being included in further clinical trials of new drugs. For participants with platinum-sensitive disease there was a considerable range of median survival times observed across the trials. The most favourable survival times and response rates were observed for paclitaxel and platinum combination therapy. This suggests that treatment with combination therapy may be more beneficial than treatment with a single-agent chemotherapeutic regimen. In terms of single-agent compounds, the evidence suggests that PLDH is more effective than topotecan. Evidence from a further trial that compared PLDH and paclitaxel suggests that there is no significant difference between these two comparators in this trial. The three comparators did, however, differ significantly in terms of their toxicity profiles across the trials. Although treatment with PLDH may therefore be more beneficial than that with topotecan, patient and physician choice as to the potential toxicities associated with each of the comparators and the patient's ability and willingness to tolerate these are of importance. Assuming the NHS is willing to pay up to pound 20,000-40,000 per additional QALY, PLDH appears to be cost-effective compared with topotecan and paclitaxel monotherapy, in terms of the overall patient population and the main subgroups considered. The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of additional trial data gave less favourable estimates for the ICER for PLDH versus paclitaxel monotherapy, compared with the base-case results. Although the ICER of PLDH compared with paclitaxel monotherapy was less favourable, PLDH was still cost-effective compared with topotecan and paclitaxel monotherapy. For platinum-sensitive patients, the combination of paclitaxel and platinum appears to be cost-effective. On the strength of the evidence reviewed here, it can be suggested that participants with platinum-resistant disease may benefit from being included in further clinical trials of new drugs. To assess the effectiveness of combination therapy against a single-agent non-platinum-based compound, it can be suggested that a trial that compared paclitaxel in combination with a platinum-based therapy versus single-agent PLDH would be a reasonable option.