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The Cochrane Database of Systematic... Dec 2013Fibromyalgia is characterized by chronic widespread pain that leads to reduced physical function. Exercise training is commonly recommended as a treatment for management... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibromyalgia is characterized by chronic widespread pain that leads to reduced physical function. Exercise training is commonly recommended as a treatment for management of symptoms. We examined the literature on resistance training for individuals with fibromyalgia. Resistance training is exercise performed against a progressive resistance with the intention of improving muscle strength, muscle endurance, muscle power, or a combination of these.
OBJECTIVES
To evaluate the benefits and harms of resistance exercise training in adults with fibromyalgia. We compared resistance training versus control and versus other types of exercise training.
SEARCH METHODS
We searched nine electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, PEDro, Dissertation Abstracts, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform, AMED) and other sources for published full-text articles. The date of the last search was 5 March 2013. Two review authors independently screened 1856 citations, 766 abstracts and 156 full-text articles. We included five studies that met our inclusion criteria.
SELECTION CRITERIA
Selection criteria included: a) randomized clinical trial, b) diagnosis of fibromyalgia based on published criteria, c) adult sample, d) full-text publication, and e) inclusion of between-group data comparing resistance training versus a control or other physical activity intervention.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently assessed risk of bias and extracted intervention and outcome data. We resolved disagreements between the two review authors and questions regarding interpretation of study methods by discussion within the pairs or when necessary the issue was taken to the full team of 11 members. We extracted 21 outcomes of which seven were designated as major outcomes: multidimensional function, self reported physical function, pain, tenderness, muscle strength, attrition rates, and adverse effects. We evaluated benefits and harms of the interventions using standardized mean differences (SMD) or mean differences (MD) or risk ratios or Peto odds ratios and 95% confidence intervals (CI). Where two or more studies provided data for an outcome, we carried out a meta-analysis.
MAIN RESULTS
The literature search yielded 1865 citations with five studies meeting the selection criteria. One of the studies that had three arms contributed data for two comparisons. In the included studies, there were 219 women participants with fibromyalgia, 95 of whom were assigned to resistance training programs. Three randomized trials compared 16 to 21 weeks of moderate- to high-intensity resistance training versus a control group. Two studies compared eight weeks of progressive resistance training (intensity as tolerated) using free weights or body weight resistance exercise versus aerobic training (ie, progressive treadmill walking, indoor and outdoor walking), and one study compared 12 weeks of low-intensity resistance training using hand weights (1 to 3 lbs (0.45 to 1.36 kg)) and elastic tubing versus flexibility exercise (static stretches to major muscle groups).Statistically significant differences (MD; 95% CI) favoring the resistance training interventions over control group(s) were found in multidimensional function (Fibromyalgia Impact Questionnaire (FIQ) total decreased 16.75 units on a 100-point scale; 95% CI -23.31 to -10.19), self reported physical function (-6.29 units on a 100-point scale; 95% CI -10.45 to -2.13), pain (-3.3 cm on a 10-cm scale; 95% CI -6.35 to -0.26), tenderness (-1.84 out of 18 tender points; 95% CI -2.6 to -1.08), and muscle strength (27.32 kg force on bilateral concentric leg extension; 95% CI 18.28 to 36.36).Differences between the resistance training group(s) and the aerobic training groups were not statistically significant for multidimensional function (5.48 on a 100-point scale; 95% CI -0.92 to 11.88), self reported physical function (-1.48 units on a 100-point scale; 95% CI -6.69 to 3.74) or tenderness (SMD -0.13; 95% CI -0.55 to 0.30). There was a statistically significant reduction in pain (0.99 cm on a 10-cm scale; 95% CI 0.31 to 1.67) favoring the aerobic groups.Statistically significant differences were found between a resistance training group and a flexibility group favoring the resistance training group for multidimensional function (-6.49 FIQ units on a 100-point scale; 95% CI -12.57 to -0.41) and pain (-0.88 cm on a 10-cm scale; 95% CI -1.57 to -0.19), but not for tenderness (-0.46 out of 18 tender points; 95% CI -1.56 to 0.64) or strength (4.77 foot pounds torque on concentric knee extension; 95% CI -2.40 to 11.94). This evidence was classified low quality due to the low number of studies and risk of bias assessment. There were no statistically significant differences in attrition rates between the interventions. In general, adverse effects were poorly recorded, but no serious adverse effects were reported. Assessment of risk of bias was hampered by poor written descriptions (eg, allocation concealment, blinding of outcome assessors). The lack of a priori protocols and lack of care provider blinding were also identified as methodologic concerns.
AUTHORS' CONCLUSIONS
The evidence (rated as low quality) suggested that moderate- and moderate- to high-intensity resistance training improves multidimensional function, pain, tenderness, and muscle strength in women with fibromyalgia. The evidence (rated as low quality) also suggested that eight weeks of aerobic exercise was superior to moderate-intensity resistance training for improving pain in women with fibromyalgia. There was low-quality evidence that 12 weeks of low-intensity resistance training was superior to flexibility exercise training in women with fibromyalgia for improvements in pain and multidimensional function. There was low-quality evidence that women with fibromyalgia can safely perform moderate- to high-resistance training.
Topics: Adult; Exercise; Female; Fibromyalgia; Humans; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 24362925
DOI: 10.1002/14651858.CD010884 -
Nutrients Sep 2023(1) Background: There has been a growing interest in understanding the causes of obesity and developing effective prevention strategies. Lifestyle change programs are... (Review)
Review
(1) Background: There has been a growing interest in understanding the causes of obesity and developing effective prevention strategies. Lifestyle change programs are often considered the gold standard for weight reduction, and they can help individuals with obesity achieve an annual weight loss of around 8-10%. The aim of this review was to evaluate the effect of food during the winter holidays. This knowledge will serve as a valuable foundation for the development of targeted interventions and prevention programs. (2) Methods: We conducted a systematic search of the literature via one database (PubMed). The search was limited to studies published in English in the last 10 years, with adult participants, but without specifying limits regarding the study design. We excluded articles that addressed intermittent fasting diets or weight loss intervention methods during the holidays through various diets. (3) In separate sections, we analyzed the psychological causes of gaining weight during the winter holidays, behavioral patterns, prevention strategies and the nutritional composition of the different types of food served during the festive period. Results: Using the combination of the terms "holiday and obesity", "holiday and weight gain", "festive season and obesity", and "festive season and weight gain" we obtained 216 results involving the addressed topic. Thus, only ten articles remained after screening, with a total of 4627 participants. Most participants experienced weight fluctuations during the study period, particularly during holidays. One concerning observation was that most of the weight gained during these periods was maintained even after the end of the studies, especially in those with obesity. A supervised exercise program and a controlled diet at work over the Christmas period are effective strategies for avoiding weight gain and its deleterious effects in people with metabolic syndrome or weight problems. (4) In addition, attention must be focused on the psycho-social factors during the holidays because for some people it is a stressful period and can cause a much higher caloric consumption. The simplest method to approach during the holidays is to implement small tips and tricks during this period that will prevent individuals from gaining extra pounds. Conclusions: It is essential to acknowledge that obesity is a multifaceted condition that requires a comprehensive and multidisciplinary approach to address its underlying factors and provide ongoing assistance to individuals in their weight-management endeavors. Even the most effective short-term interventions are likely to produce continued positive outcomes with persistent intervention and support.
Topics: Adult; Humans; Holidays; Seasons; Obesity; Weight Gain; Feeding Behavior; Weight Loss
PubMed: 37836485
DOI: 10.3390/nu15194201 -
Health Technology Assessment... 2003To establish the clinical and cost-effectiveness of amantadine, oseltamivir and zanamivir compared to standard care for the treatment and prevention of influenza. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To establish the clinical and cost-effectiveness of amantadine, oseltamivir and zanamivir compared to standard care for the treatment and prevention of influenza.
DATA SOURCES
Electronic databases. Reference lists of identified articles and key publications. Relevant trials.
REVIEW METHODS
A systematic review and meta-analysis of the randomised evidence was undertaken to investigate the effectiveness of oseltamivir and zanamivir compared to standard care for treatment and prophylaxis use for influenza A and B. An additional systematic review of the effectiveness of amantadine for treatment and prophylaxis use for influenza A in children and the elderly was also undertaken. Economic decision models were constructed to examine the cost-effectiveness and cost-utility of the alternative strategies for treating and preventing influenza A and/or B. This was informed by the systematic reviews outlined above and additional sources of information where required.
RESULTS
The systematic review of the treatment of influenza found that oseltamivir reduced the median duration of symptoms in the influenza positive group by 1.38 days for the otherwise healthy adult population, 0.5 day for the high-risk population, and 1.5 days for the children population. This compared to 1.26 days, 1.99 days, and 1.3 for the similar groups for inhaled zanamivir. The systematic review of the prevention of influenza found that the relative risk reduction for oseltamivir was between approximately 75 and 90% and approximately 70 and 90% for inhaled zanamivir depending on the strategy adopted and the population under consideration. For the economic model a base case was constructed that focussed primarily on the health benefits generated by shortening the period of influenza illness. This base case found that, compared to standard care, the estimated cost per quality-adjusted life year ranged from pound 6190 to pound 31,529 for healthy adults, from pound 4535 to pound 22,502 for the 'high-risk' group, from pound 6117 to pound 30,825 for children, and from pound 5057 to pound 21,781 for the residential care elderly population. The base case model included valuations of the health effects of pneumonia (and otitis media in the children's model) based on observed rates in the trials. However it does not include the cost of hospitalisations as only very limited data was available for the effects of antivirals on hospitalisation rates. As for mortality rates, deaths from influenza were rare in trials of neuraminidase inhibitors (NIs). Therefore, suitable data on mortality were not available from these sources. As avoided hospitalisation costs and avoided mortality are potentially important we also carried out sensitivity analysis that involved extrapolating the observed reductions in pneumonias in the NI trials to hospitalisations and deaths. In all four models the cost-effectiveness of NIs is substantially improved by this extrapolation. For prophylaxis, antiviral drugs were compared with vaccination as preventative strategies. In all cases the cost-effectiveness ratios for vaccination were either low or cost-saving. In the base case the cost-effectiveness of antivirals was relatively unfavourable, there were scenarios relating to the elderly residential care model where antivirals as an additional strategy could be cost-effective.
CONCLUSIONS
The cost-effectiveness varies markedly between the intervention strategies and target populations. The estimate of cost effectiveness is also sensitive to variations in certain key parameters of the model, for example the proportion of all influenza-like illnesses that are influenza. The effectiveness literature that was used to inform the economic decision model spans many decades and hence great caution should be exercised when interpreting the results of indirect intervention comparisons from the model. Further randomised trials making direct comparisons would be valuable to verify the model's findings.
Topics: Antiviral Agents; Cost-Benefit Analysis; Decision Support Techniques; Humans; Influenza Vaccines; Influenza, Human; Quality-Adjusted Life Years; Treatment Outcome
PubMed: 14609480
DOI: 10.3310/hta7350 -
Health Technology Assessment... Aug 2010To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling.
DATA SOURCES
The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database.
STUDY SELECTION
The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI.
DATA EXTRACTION
Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person.
RESULTS
Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when society's willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions.
LIMITATIONS
Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies.
CONCLUSIONS
More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies.
Topics: Adrenergic Uptake Inhibitors; Biofeedback, Psychology; Cost-Benefit Analysis; Electric Stimulation Therapy; Exercise Therapy; Female; Humans; Life Style; Markov Chains; Models, Economic; Pelvic Floor; Quality-Adjusted Life Years; Risk Factors; Selective Serotonin Reuptake Inhibitors; Stress, Psychological; Suburethral Slings; Treatment Outcome; United Kingdom; Urinary Incontinence, Stress
PubMed: 20738930
DOI: 10.3310/hta14400 -
Harm Reduction Journal Nov 2021Several published systematic reviews have examined the potential associations between e-cigarette use and cigarette smoking, but their methodological and/or reporting... (Review)
Review
Reporting and methodological quality of systematic literature reviews evaluating the associations between e-cigarette use and cigarette smoking behaviors: a systematic quality review.
INTRODUCTION
Several published systematic reviews have examined the potential associations between e-cigarette use and cigarette smoking, but their methodological and/or reporting quality have not yet been assessed. This systematic quality review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2 to evaluate the quality of systematic reviews investigating potential associations between e-cigarette use and cigarette smoking.
MATERIALS AND METHODS
PubMed/MEDLINE, Embase, and PsycINFO were searched from 01 January 2007 to 24 June 2020. Methodological quality was assessed using AMSTAR 2, and reporting quality was assessed using PRISMA guidelines.
RESULTS
Of 331 potentially relevant systematic reviews, 20 met predefined inclusion criteria. Most reviews (n = 15; 75%) reported on e-cigarette use and cigarette smoking cessation, while three reported on e-cigarette use and cigarette smoking initiation (15%); and two reported on cigarette smoking initiation and cessation (10%). According to AMSTAR 2 guidelines, 18 of the 20 reviews (90%) were "critically low" in overall confidence of the results, while two were ranked "low." Additionally, reporting quality varied across the reviews, with only 60% reporting at least half of the PRISMA items.
DISCUSSION
Methodological limitations were identified across reviews examining potential associations between e-cigarette use and cigarette smoking behaviors, indicating that findings from these reviews should be interpreted with caution.
CONCLUSIONS
Future systematic reviews in this field should strive to adhere to AMSTAR 2 and PRISMA guidelines, to provide high quality syntheses of the available data with transparent and complete reporting.
Topics: Cigarette Smoking; Electronic Nicotine Delivery Systems; Humans; Research Report; Vaping
PubMed: 34838030
DOI: 10.1186/s12954-021-00570-9 -
Health Technology Assessment... May 2006To assess the effectiveness and cost-effectiveness of HealOzone (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The... (Review)
Review
OBJECTIVES
To assess the effectiveness and cost-effectiveness of HealOzone (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a 'patient kit', which consists of toothpaste, oral rinse and oral spray all containing fluoride.
DATA SOURCES
Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002).
REVIEW METHODS
A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries.
RESULTS
Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies' findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (40.49 pounds versus 24.78 pounds), but cost less for non-cavitated root caries ( 14.63 pounds versus 21.45 pounds). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator ( 22.65 pounds versus 33.39 pounds).
CONCLUSIONS
Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cost-Benefit Analysis; Dental Caries; Female; Health Surveys; Humans; Male; Middle Aged; Ozone; Randomized Controlled Trials as Topic; Root Caries; State Medicine; Treatment Outcome; United Kingdom
PubMed: 16707073
DOI: 10.3310/hta10160 -
Health Technology Assessment... 2001Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the... (Comparative Study)
Comparative Study Review
BACKGROUND
Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the early stages of the disease, most cases are not detected until the advanced stages. Consequently, the prognosis after diagnosis is poor and the 5-year survival rate in the UK is only about 30%. Current recommendations suggest that first-line chemotherapy for ovarian cancer should involve paclitaxel and platinum (Pt)-based therapy (cisplatin/ carboplatin), however, most patients develop resistant or refractory disease and require second-line therapy. Patients may respond to re-challenge with Pt-agents if the treatment-free interval is > 6 months, but an alternative is often required. Topotecan is one of six drugs currently licensed in the UK for second-line therapy, and recent reviews suggest that it has modest efficacy in the treatment of advanced disease and performs favourably against paclitaxel. However, these reviews are based on a limited number of reports mainly consisting of non-randomised Phase I and II studies.
OBJECTIVES OF THE REVIEW
To examine the clinical effectiveness and cost-effectiveness of oral and intravenous topotecan (Hycamtin, SmithKline Beecham, UK) for the treatment of all stages of ovarian cancer.
SEARCH STRATEGY
Sixteen electronic databases from inception to September 2000 and Internet resources were searched, in addition to the bibliographies of retrieved articles and submissions from pharmaceutical companies.
INCLUSION AND EXCLUSION CRITERIA
Two reviewers independently screened all titles/abstracts and included/excluded studies based on full copies of manuscripts. Any disagreements were resolved through discussion. Only randomised controlled trials (RCTs) and full economic evaluations comparing topotecan to non-topotecan regimens were included. All stages of therapy and disease were considered, and the outcomes included were survival, response, symptom relief, quality of life, adverse effects and costs.
METHODS
DATA EXTRACTION STRATEGY: Data were extracted into an Access database by one reviewer and checked by a second. Any disagreements were resolved through discussion.
METHODS
QUALITY ASSESSMENT STRATEGY: Two reviewers, using specified criteria, independently assessed the quality of the clinical effectiveness studies and the economic evaluations. Any disagreements were resolved through discussion.
METHODS
ANALYSIS STRATEGY: Due to the limited number of studies included in the review and the fact that they compared topotecan with different comparators, the out-come data could not be pooled statistically. Clinical effectiveness data are discussed separately under the different outcome subheadings. For time-to-event data, hazard ratios with 95% confidence intervals are presented where available, and for the remaining outcomes, relative risks are reported or calculated where sufficient data were available. Relative risk data are also presented in the form of Forest plots without pooled estimates. Economic data are presented in the form of a summary and critique of the evidence, and a grading (A-I) assigned to each study indicating the direction and magnitude of the cost-effectiveness data.
INCLUDED STUDIES
A total of 568 titles/abstracts were identified and screened for relevance. Full copies of 72 papers were assessed and seven published manuscripts reporting details of two studies of clinical effectiveness and one economic evaluation were included. Further details of the two clinical effectiveness studies and two new economic evaluations were identified from confidential company submissions. Overall, two international multicentre RCTs of effectiveness comparing topotecan with paclitaxel (trial 039) and topotecan with caelyx (trial 30-49) were included in the review. The three economic evaluations included in the review comprised one cost-minimisation analysis (CMA) comparing topotecan with caelyx, one cost-consequences analysis (CCA) comparing topotecan with paclitaxel, etoposide and altretamine and one cost-effectiveness analysis (CEA) comparing topotecan with paclitaxel.
RESULTS
QUALITY OF CLINICAL EFFECTIVENESS DATA: Both clinical effectiveness studies (trial 30-49 and 039) were of reasonable quality, although it was unclear whether either performed valid intention-to-treat analyses. In addition, trial 30-49 failed to state whether the outcome assessors were blinded to treatment allocation. RESULTS --QUALITY OF ECONOMIC EVALUATIONS: The CCA (comparing topotecan with three comparators) was of poor quality and of little relevance to the UK NHS. The CMA and CEA were of reasonable quality overall and relevant to the UK NHS. However, both, in particular the CEA, suffered from methodological problems, and thus their findings should be interpreted with caution.
RESULTS
ASSESSMENT OF CLINICAL EFFECTIVENESS: The assessment of clinical effectiveness was based on limited data. Only two trials with a total of 709 participants were identified. In general, with a few minor exceptions, there were no statistically significant differences between topotecan and paclitaxel, or topotecan and caelyx in survival, response rate, median time to response, median duration of response and quality of life. Significant differences that were reported were mainly identified in subgroup analyses (Pt-sensitive disease and disease without ascites) of questionable validity and their relevance to a general advanced ovarian cancer patient population undergoing second-line chemotherapy is unclear. However, statistically significant differences were observed in the incidence of adverse effects. Topotecan was associated with increased incidences of haematological toxicities (including neutropenia, leukopenia, anaemia and thrombocytopenia), alopecia, nausea and vomiting. Caelyx-treated patients suffered from significantly increased incidences of Palmar-Plantar erythrodysesthesia, stomatitis, mucous membrane disorders and skin rashes. Paclitaxel was associated with significant increases in alopecia, arthralgia, myalgia, neuropathy, paraesthesiae, skeletal pain and flushing.
RESULTS
ASSESSMENT OF COST-EFFECTIVENESS: The assessment of cost-effectiveness was also based on limited data, with three evaluations identified, one of which was not relevant. The two remaining studies, comparing topotecan with paclitaxel (CEA) and topotecan with caelyx (CMA), both used effectiveness data from multicentre RCTs and based their costs on 1999/2000 UK sources. The evaluations were conducted from a UK NHS perspective and findings presented in GB pounds/Euros. Topotecan for the second-line treatment of advanced ovarian cancer was shown to be more cost-effective than paclitaxel (32,513 GB pounds versus 46,186 GB pounds per person in terms of any response (complete or partial), incremental cost-effectiveness = 3065 GB pounds) in all respects except cost per time without toxicity or symptoms, but less cost-effective than caelyx (14,023 GB pounds versus 9979 GB pounds per person regardless of whether the patient responded). However, direct comparisons of the cost findings between the two studies is difficult because they used different designs, different time horizons for the cost analyses and the findings were presented as costs per person for only patients who responded in one study (topotecan versus paclitaxel) and costs per person regardless of whether they responded in the other study (topotecan versus caelyx).
CONCLUSIONS
This review indicates that there is little evidence in the form of RCTs on which to base an assessment of the effectiveness of topotecan as second-line therapy for advanced ovarian cancer. The evidence suggests there were no statistically significant differences overall between topotecan and paclitaxel, or topotecan and caelyx in clinical outcomes. However, statistically significant differences were observed in the incidence of adverse effects. The clinical significance of the findings is not discussed. Overall, the effects of topotecan could at best be described as modest, but the alternative agents offer no real advantages except fewer side-effects and possibly improved cost-effectiveness. Both of the clinical effectiveness studies on which this evidence is based had methodological flaws, the most serious being the lack of a blinded assessor in the topotecan versus caelyx trial, which is important for unbiased assessment of response outcomes. The economic evaluations also suffered from a number of potential problems.
CONCLUSIONS
RECOMMENDATIONS FOR RESEARCH: Further good quality RCTs and CEAs are required comparing topotecan with other licensed and potentially useful (soon to be licensed) second-line treatments for ovarian cancer. At present, it is difficult to make any decisions about topotecan and other drugs for second-line therapy without good quality direct comparisons. In view of the ongoing studies identified, an update of the current review should be considered in approximately 18 months (Summer 2002) or possibly sooner if the recently commissioned National Institute for Clinical Excellence review of caelyx for ovarian cancer identifies additional data relevant to topotecan.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Female; Humans; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Technology Assessment, Biomedical; Topotecan
PubMed: 11701100
DOI: 10.3310/hta5280 -
BMJ (Clinical Research Ed.) Jul 2002To quantify the effects of smoke-free workplaces on smoking in employees and compare these effects to those achieved through tax increases. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To quantify the effects of smoke-free workplaces on smoking in employees and compare these effects to those achieved through tax increases.
DESIGN
Systematic review with a random effects meta-analysis.
STUDY SELECTION
26 studies on the effects of smoke-free workplaces.
SETTING
Workplaces in the United States, Australia, Canada, and Germany.
PARTICIPANTS
Employees in unrestricted and totally smoke-free workplaces.
MAIN OUTCOME MEASURES
Daily cigarette consumption (per smoker and per employee) and smoking prevalence.
RESULTS
Totally smoke-free workplaces are associated with reductions in prevalence of smoking of 3.8% (95% confidence interval 2.8% to 4.7%) and 3.1 (2.4 to 3.8) fewer cigarettes smoked per day per continuing smoker. Combination of the effects of reduced prevalence and lower consumption per continuing smoker yields a mean reduction of 1.3 cigarettes per day per employee, which corresponds to a relative reduction of 29%. To achieve similar reductions the tax on a pack of cigarettes would have to increase from $0.76 to $3.05 (0.78 euro to 3.14 euro) in the United States and from 3.44 pounds sterling to 6.59 pounds sterling (5.32 euro to 10.20 euro) in the United Kingdom. If all workplaces became smoke-free, consumption per capita in the entire population would drop by 4.5% in the United States and 7.6% in the United Kingdom, costing the tobacco industry $1.7 billion and 310 million pounds sterling annually in lost sales. To achieve similar reductions tax per pack would have to increase to $1.11 and 4.26 pounds sterling.
CONCLUSIONS
Smoke-free workplaces not only protect non-smokers from the dangers of passive smoking, they also encourage smokers to quit or to reduce consumption.
Topics: Adolescent; Humans; Occupational Health; Smoking; Smoking Cessation; Smoking Prevention; Tobacco Smoke Pollution; Workplace
PubMed: 12142305
DOI: 10.1136/bmj.325.7357.188 -
Health Technology Assessment... Jan 2010To assess the clinical effectiveness and cost-effectiveness of bevacizumab, combined with interferon (IFN), sorafenib tosylate, sunitinib and temsirolimus in the... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of bevacizumab, combined with interferon (IFN), sorafenib tosylate, sunitinib and temsirolimus in the treatment of people with advanced and/or metastatic renal cell carcinoma (RCC).
DATA SOURCES
Electronic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched up to September/October 2007 (and again in February 2008).
REVIEW METHODS
Systematic reviews and randomised clinical trials comparing any of the interventions with any of the comparators in participants with advanced and/or metastatic RCC were included, also phase II studies and conference abstracts if there was sufficient detail to adequately assess quality. Results were synthesised narratively and a decision-analytic Markov-type model was developed to simulate disease progression and estimate the cost-effectiveness of the interventions under consideration.
RESULTS
A total of 888 titles and abstracts were retrieved in the clinical effectiveness review, including reports of eight clinical trials. Treatment with bevacizumab plus IFN or sunitinib had clinically relevant and statistically significant advantages over treatment with IFN alone, in terms of progression-free survival and tumour response, doubling median progression-free survival from approximately 5 months to 10 months. Temsirolimus had similar advantages over treatment with IFN in terms of progression-free and overall survival, increasing median overall survival from 7.3 to 10.9 months [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58 to 0.92)], as did sorafenib in comparison with best supportive care in terms of overall survival, progression-free survival and tumour response, with a doubling of progression-free survival (HR 0.51; 95% CI 0.43 to 0.60). However, the last was associated with an increased frequency of hypertension and hand-foot skin reaction compared with placebo. No fully published economic evaluations of any of the interventions could be located. However, estimates from the PenTAG model suggested that none of the interventions would be considered cost-effective at a willingness-to-pay threshold of 30,000 pounds per quality-adjusted life-year (QALY). Estimates of cost per QALY ranged from 71,462 pounds for sunitinib to 171,301 pounds for bevacizumab plus IFN. Although there are many similarities in the methodology and structural assumptions employed by PenTAG and the manufacturers of the interventions, in all cases the cost-effectiveness estimates from the PenTAG model were higher than those presented in the manufacturers' submissions. Cost-effectiveness estimates were particularly sensitive to variations in the estimates of treatment effectiveness, drug pricing (including dose intensity data), and health-state utility input parameters.
CONCLUSIONS
Treatment with bevacizumab plus IFN and sunitinib has clinically relevant and statistically significant advantages over treatment with IFN alone in patients with metastatic RCC. In people with three of six risk factors for poor prognosis, temsirolimus had clinically relevant advantages over treatment with IFN, and sorafenib tosylate was superior to best supportive care as second-line therapy. The frequency of adverse events associated with bevacizumab plus IFN, sunitinib and temsirolimus was comparable with that seen with IFN, although the adverse event profile is different. Treatment with sorafenib was associated with a significantly increased frequency of hypertension and hand-foot syndrome. Estimates from the PenTAG model suggested that none of the interventions would be considered cost-effective at a willingness-to-pay threshold of 30,000 pounds per QALY.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Bevacizumab; Carcinoma, Renal Cell; Cost-Benefit Analysis; Humans; Indoles; Kidney Neoplasms; Niacinamide; Phenylurea Compounds; Pyridines; Pyrroles; Sirolimus; Sorafenib; Sunitinib
PubMed: 20028613
DOI: 10.3310/hta14020 -
Health Technology Assessment... May 2004To undertake a systematic review of the long-term effects of obesity treatments on body weight, risk factors for disease, and disease. (Review)
Review
OBJECTIVES
To undertake a systematic review of the long-term effects of obesity treatments on body weight, risk factors for disease, and disease.
METHODS
The study encompassed three systematic reviews that examined different aspects of obesity treatments. (1) A systematic review of obesity treatments in adults where the methods of the Cochrane Collaboration were applied and randomised controlled trials (RCTs) with a follow-up of at least 1 year were evaluated. (2) A systematic epidemiological review, where studies were sought on long-term effects of weight loss on morbidity and/or mortality, and examined through epidemiological modelling. (3) A systematic economic review that sought reports with both costs and outcomes of treatment, including recent reports that assessed the cost-effectiveness of pharmaceutical and surgical interventions. A Markov model was also adopted to examine the cost-effectiveness of a low-fat diet and exercise intervention in adults with obesity and impaired glucose tolerance.
RESULTS
The addition of the drugs orlistat or sibutramine was associated with weight loss and generally improved risk factors, apart from diastolic blood pressure for sibutramine. Metformin was associated with decreased mortality after 10 years in obese people with type 2 diabetes. Low-fat diets were associated with continuing weight loss for 3 years and improvements in risk factors, as well as prevention of type 2 diabetes and improved control of hypertension. Insufficient evidence was available to demonstrate the benefits of low calorie or very low calorie diets. The addition of an exercise or behaviour programme to diet was associated with improved weight loss and risk factors for at least 1 year. Studies combining low-fat diets, exercise and behaviour therapy suggested improved hypertension and cardiovascular disease. Family therapy was associated with improved weight loss for 2 years compared to individual therapy. There was insufficient evidence to conclude that individual therapy was more beneficial than group therapy. Weight lost more quickly (within 1 year), from the epidemiology review, may be more beneficial with respect to the risk of mortality. The effects of intentional weight loss need further investigation. Weight loss from surgical and non-surgical interventions for people suffering from obesity was associated with decreased risk of development of diabetes, and a reduction in low-density lipoprotein cholesterol, total cholesterol and blood pressure, in the long term. Targeting high-risk individuals with drugs or surgery was likely to result in a cost per additional life-year or quality-adjusted life-year (QALY) of no more than 13,000 British pounds. There was also suggestive evidence of cost saving from treatment of people with type 2 diabetes with metformin. Targeting surgery on people with severe obesity and impaired glucose tolerance was likely to be more cost-effective at 2329 British pounds per additional life-year. Economic modelling over 6 years for diet and exercise for people with impaired glucose tolerance was associated with a high initial cost per additional QALY, but by the sixth year the cost per QALY was 13,389 British pounds. Results did not include cost savings from diseases other than diabetes, and therefore may be conservative.
CONCLUSIONS
The drugs orlistat and sibutramine appear beneficial for the treatment of adults with obesity, and metformin for obese patients with type 2 diabetes. Exercise and/or behaviour therapy appear to improve weight loss when added to diet. Low-fat diets with exercise, or with exercise and behaviour therapy are associated with the prevention of type 2 diabetes and hypertension. Long-term weight loss in epidemiological studies was associated with reduced risk of type 2 diabetes, and may be beneficial for cardiovascular disease. Low-fat diets and exercise interventions in individuals at risk of obesity-related illness are of comparable cost to drug treatments. Long-term pragmatic RCTs of obesity treatments in populations with obesity-related illness or at high risk of developing such illness are needed (to include an evaluation of risk factors, morbidity, quality of life and economic evaluations). Drug trials that include dietary advice, plus exercise and/or behaviour therapy are also needed. Research exploring effective types of exercise, diet or behaviour and also interventions to prevent obesity in adults is required.
Topics: Anti-Obesity Agents; Behavior Therapy; Caloric Restriction; Cost-Benefit Analysis; Cyclobutanes; Diet, Fat-Restricted; Humans; Hypoglycemic Agents; Lactones; Markov Chains; Metformin; Obesity; Orlistat; Physical Fitness; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 15147610
DOI: 10.3310/hta8210