Geoff K Frampton

The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: a systematic review.

OBJECTIVE To assess the long-term clinical effectiveness and cost-effectiveness of multicomponent weight management schemes for adults in terms of weight loss and maintenance of weight loss. DATA SOURCES Bibliographic databases were searched from inception to December 2009, including the Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences and symposia were searched and experts were contacted to identify additional published and unpublished references. REVIEW METHODS For the clinical effectiveness review, two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers by one reviewer and checked by a second reviewer using a pre-piloted inclusion flow chart. The studies were long-term randomised controlled trials (RCTs) of adult participants who were classified by body mass index as overweight or obese. Interventions were multicomponent weight management programmes (including diet, physical activity and behaviour change strategies) that assessed weight measures. Programmes that involved the use of over-the-counter medicines licensed in the UK were also eligible. For the cost-effectiveness review two reviewers independently screened studies for inclusion. Cost-effectiveness, cost-utility, cost-benefit or cost-consequence analyses were eligible. Data were extracted using a standardised and pre-piloted data extraction form. The quality of included studies was assessed using standard criteria. Studies were synthesised through a narrative review with full tabulation of results. RESULTS A total of 3358 references were identified, of which 12 were included in the clinical effectiveness review. Five RCTs compared multicomponent interventions with non-active comparator groups. In general, weight loss appeared to be greater in the intervention groups than in the comparator groups. Two RCTs compared multicomponent interventions that focused on the diet component. In these studies there were no statistically significant differences in weight loss between interventions. Four RCTs compared multicomponent interventions that focused on the physical activity component. There was little consistency in the pattern of results seen, in part owing to the differences in the interventions. In one RCT the intervention focused on the goal-setting interval and it appeared that weight loss was greatest in those given daily goals compared with weekly goals. Overall, where measured, it appeared that most groups began to regain weight at further follow-up. Of the 419 studies identified in the cost-effectiveness searches, none met the full inclusion criteria. Two economic evaluations are described in our review; however, caution is required in their interpretation, as they did not meet all inclusion criteria. Lifetime chronic disease models were used in these studies and the models included the costs and benefits of avoiding chronic illness. Both studies found the interventions to be cost-effective, with estimates varying between -£473 and £7200 (US

Effects of pesticides on soil invertebrates in laboratory studies: A review and analysis using species sensitivity distributions

12,640) per quality-adjusted life-year gained; methodological omissions from these studies were apparent and caution is therefore required in the interpretation of these results. CONCLUSIONS Long-term multicomponent weight management interventions were generally shown to promote weight loss in overweight or obese adults. Weight changes were small however and weight regain was common. There were few similarities between the included studies; consequently an overall interpretation of the results was difficult to make. There is some evidence that weight management interventions are likely to be cost-effective, although caution is required as there were some limitations in the two cost-evaluation studies described. FUNDING The National Institute for Health Research Health Technology Assessment programme.

The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13-19: a systematic review and economic evaluation

Species sensitivity distributions (SSD) and 5% hazardous concentrations (HC5) are distribution-based approaches for assessing environmental risks of pollutants. These methods have potential for application in pesticide risk assessments, but their applicability for assessing pesticide risks to soil invertebrate communities has not been evaluated. Using data obtained in a systematic review, the present study investigates the relevance of SSD and HC5 for predicting pesticide risks to soil invertebrates. Altogether, 1950 laboratory toxicity data were obtained, representing 250 pesticides and 67 invertebrate taxa. The majority (96%) of pesticides have toxicity data for fewer than five species. Based on a minimum of five species, the best available endpoint data (acute mortality median lethal concentration) enabled SSD and HC5 to be calculated for 11 pesticides (atrazine, carbendazim, chlorpyrifos, copper compounds, diazinon, dimethoate, gamma-hexachlorocyclohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). Arthropods and oligochaetes exhibit pronounced differences in their sensitivity to most of these pesticides. The standard test earthworm species, Eisenia fetida sensu lato, is the species that is least sensitive to insecticides based on acute mortality, whereas the standard Collembola test species, Folsomia candida, is among the most sensitive species for a broad range of toxic modes of action (biocide, fungicide, herbicide, and insecticide). These findings suggest that soil arthropods should be tested routinely in regulatory risk assessments. In addition, the data indicate that the uncertainty factor for earthworm acute mortality tests (i.e., 10) does not fully cover the range of earthworm species sensitivities and that acute mortality tests would not provide the most sensitive risk estimate for earthworms in the majority (95%) of cases.

Effects of pesticides on soil invertebrates in model ecosystem and field studies: a review and comparison with laboratory toxicity data

OBJECTIVES To assess the effectiveness and cost-effectiveness of schools-based skills-building behavioural interventions to encourage young people to adopt and maintain safer sexual behaviour and to prevent them from acquiring sexually transmitted infections (STIs). DATA SOURCES Electronic bibliographic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, PsycINFO, CCRCT, NHS EED and DARE) were searched for the period 1985 to March 2008. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify additional published and unpublished references. REVIEW METHODS A systematic review of effectiveness and economic evaluation of cost-effectiveness were carried out. A descriptive map of studies that met inclusion criteria was produced, and keywords were developed and systematically applied to these studies to identify a policy-relevant subset of studies for the systematic review. Outcome data for variables including sexual behaviour were extracted. An economic model was developed to compare the costs and consequences of the behavioural interventions. A Bernoulli statistical model was constructed to describe the probability of STI infection. RESULTS There were few significant differences between the interventions and comparators in terms of changes in sexual behaviour outcomes, although there were some significant differences for knowledge and some measures of self-efficacy. The studies included in this review conducted relatively short follow-up assessments at a time when many young people were becoming sexually active. It is therefore possible that favourable behaviour change may have occurred, and become more cost-effective, with time, as sexual activity becomes more routine in young peoples lives. The quality of the intervention provider influenced whether or not young people found the interventions to be acceptable and engaging; enthusiasm and considerable expertise were important for effective class management and delivery of skills-building activities, and a supportive school culture was also helpful. Recognition of young peoples individual needs in relation to sexual health was another important factor. No conclusions could be drawn on the impact of the interventions on sexual health inequalities due to a lack of relevant data on socioeconomic status, gender and ethnicity. The results of the economic evaluation were considered to be illustrative, mainly due to the uncertainty of the effect of intervention on behavioural outcomes. The results were most sensitive to changes in parameter values for the intervention effect, the transmission probability of STIs and the number of sexual partners. The costs of teacher-led and peer-led behavioural interventions, based on the resources estimated from the relevant randomised controlled trials in our systematic review, were 4.30 pounds and 15 pounds per pupil, respectively. Teacher-led interventions were more cost-effective than peer-led interventions due to the less frequent need for training. The incremental cost-effectiveness of the teacher-led and peer-led interventions was 20,223 pounds and 80,782 pounds per quality-adjusted life-year gained, respectively. An analysis of individual parameters revealed that future research funding should focus on assessing the intervention effect for condom use from a school-based intervention. CONCLUSIONS School-based behavioural interventions for the prevention of STIs in young people can bring about improvements in knowledge and increased self-efficacy, but the interventions did not significantly influence sexual risk-taking behaviour or infection rates. Future investigation should include long-term follow-up to assess the extent to which safer sexual behaviour is adopted and maintained into adulthood, and prospective cohort studies are needed to look at the parameters that describe the transmission of STIs between partners. Funding should focus on the effectiveness of the interventions on influencing behaviour.

Epigeic Collembola in winter wheat under organic, integrated and conventional farm management regimes

A systematic review was carried out to investigate the extent to which higher-tier (terrestrial model ecosystem [TME] and field) data regarding pesticide effects can be compared with laboratory toxicity data for soil invertebrates. Data in the public domain yielded 970 toxicity endpoint data sets, representing 71 pesticides and 42 soil invertebrate species or groups. For most pesticides, the most frequent effect class was for no observed effects, although relatively high numbers of pronounced and persistent effects occurred when Lumbricidae and Enchytraeidae were exposed to fungicides and when Lumbricidae, Collembola, and Arachnida were exposed to insecticides. No effects of fungicides on Arachnida, Formicidae, or Nematoda or of herbicides on Lumbricidae, Formicidae, or Nematoda were observed in any studies. For most pesticides, higher-tier no-observed-effect concentration or lowest-observed-effect concentration values cannot be determined because of a lack of information at low pesticide concentrations. Ten pesticides had sufficient laboratory data to enable the observed higher-tier effects to be compared with 5% hazardous concentrations (HC5) estimated from acute toxicity laboratory data (atrazine, carbendazim, chlorpyrifos, diazinon, dimethoate, gamma-hexachlorocy-clohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). In eight cases, higher-tier effects concentrations were within or below the 90% confidence interval of the HC5. Good agreement exists between the results of TME and field tests for carbendazim, but insufficient information is available for a comparison between TME and field studies for other pesticides. Availability and characteristics (e.g., taxonomic composition and heterogeneity) of the higher-tier effects data are discussed in terms of possible developments in risk assessment procedures.

Assessing the effects of plant protection products on organic matter breakdown in arable fields—litter decomposition test systems

Community characteristics of Collembola assemblages in conventional, integrated and organic fields of winter wheat were compared among three randomly chosen areas in England using analysis of similarities, cluster analysis, multi-dimensional scaling and several measures of diversity and evenness. Indicator values were used to identify indicator species. Significant differences were found in the abundance of most species and in community structure among the three geographical regions but few differences between the farming regimes were significant. Despite a lack of significant differences among regimes, Entomobrya multifasciata and Isotomurus spp. were consistently, although not significantly more common in conventional than organic fields whereas the opposite was true for Isotoma viridis and Isotoma notabilis. Farming regime significantly affected the abundance of Sminthurinus elegans and Sminthurus viridis but the effect differed between geographical regions. Community composition and species dominance were influenced by farming regime, but no species were indicative of the different farming systems, as most occurred ubiquitously in all fields. Organically and conventionally farmed fields were found not to differ significantly from each other in community composition, but both differed from integrated fields. These findings are compared with the results from other recent European studies of the effects of farming systems on arthropods and their wider ecological implications are discussed.

Effects of spring precipitation on a temperate arable collembolan community analysed using Principal Response Curves

There is a need for plant protection products (PPPs) to be assessed for their effects on the breakdown of organic matter (OM), which is an important functional process in terrestrial ecosystems. Little information is available on to how to assess effects of PPPs on this complex system and formal guidelines for a standardised test method are lacking. We critically reviewed the literature to determine appropriate methods to investigate OM breakdown for the risk assessment of PPPs. Five methods appeared to be potentially suitable: namely the use of mini-containers or litter-bags to enclose OM, cotton-strip and bait-lamina assays which provide an artificial OM substrate, and stable isotopes to track the chemical decomposition of OM. These methods were compared on the basis of 10 suitability criteria, which included ecological relevance, ease of use and relevance to risk assessors. Each test method has limitations but the use of litter-bags, which is the most frequently used method, has distinct advantages over the other approaches. Accordingly, literature describing OM breakdown in litter-bags when applying PPPs are reviewed, gaps in the methodology are highlighted and recommendations for the development of a standardised and validated test method are proposed.

Entecavir for the treatment of chronic hepatitis B infection

We hypothesized that changes in the pattern of spring precipitation would alter the species composition of a temperate soil-surface collembolan community. Experimental manipulation of precipitation during a drought in southern England was used to test this hypothesis in spring 1997. Replicated plots in a field of spring peas received spring drought (plots shielded from rainfall), reference (actual) rainfall and spring irrigation during the first 2 weeks of May. Shielding plots extended the existing drought to 58 days. Thereafter all plots received natural precipitation only, which in June considerably exceeded the long-term average for the site. Redundancy Analysis (RDA) and the recently-developed method of Principal Response Curves analysis (PRC) were used to summarise and test statistically changes in community composition under the three precipitation treatments, using counts of soil-surface species obtained by suction sampling. Irrigation decreased counts of Bourletiella hortensis, but had a positive impact on all other species studied, whilst the effect of spring drought was negative. Effects of spring precipitation persisted for the 97-day duration of the study despite the unusually wet summer. The possibility that changes in patterns of rainfall in northern Europe would promote some species as crop pests is proposed, but not supported by our findings. We use the collembolan data to illustrate some advantages of PRC analysis over RDA and other ordination techniques for analysing community responses to experimental treatments.

Selecting appropriate methods of knowledge synthesis to inform biodiversity policy

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturers submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturers mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturers lifetime treatment scenario for HBeAg-negative patients and the ERGs 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.

The clinical effectiveness and cost-effectiveness of second-eye cataract surgery: a systematic review and economic evaluation

Responding to different questions generated by biodiversity and ecosystem services policy or management requires different forms of knowledge (e.g. scientific, experiential) and knowledge synthesis. Additionally, synthesis methods need to be appropriate to policy context (e.g. question types, budget, timeframe, output type, required scientific rigour). In this paper we present a range of different methods that could potentially be used to conduct a knowledge synthesis in response to questions arising from knowledge needs of decision makers on biodiversity and ecosystem services policy and management. Through a series of workshops attended by natural and social scientists and decision makers we compiled a range of question types, different policy contexts and potential methodological approaches to knowledge synthesis. Methods are derived from both natural and social sciences fields and reflect the range of question and study types that may be relevant for syntheses. Knowledge can be available either in qualitative or quantitative form and in some cases also mixed. All methods have their strengths and weaknesses and we discuss a sample of these to illustrate the need for diversity and importance of appropriate selection. To summarize this collection, we present a table that identifies potential methods matched to different combinations of question types and policy contexts, aimed at assisting teams undertaking knowledge syntheses to select appropriate methods.