Adalimumab for Treating Moderate-to-Severe Hidradenitis Suppurativa: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company’s submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company’s submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy

MRCP compared to diagnostic ERCP for diagnosis when biliary obstruction is suspected: a systematic review

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an alternative to diagnostic endoscopic retrograde cholangiopancreatography (ERCP) for investigating biliary obstruction. The use of MRCP, a non-invasive procedure, may prevent the use of unnecessary invasive procedures. The aim of the study was to compare the findings of MRCP with those of ERCP by the computation of accuracy statistics. METHODS: Thirteen electronic bibliographic databases, covering biomedical, science, health economics and grey literature were searched. A systematic review of studies comparing MRCP to diagnostic ERCP in patients with suspected biliary obstruction was conducted. Sensitivity, specificity, likelihood ratios, acceptability and adverse events were reported. RESULTS: 25 studies were identified reporting several conditions including choledocholithiasis (18 studies), malignancy (four studies), obstruction (three studies), stricture (two studies) and dilatation (five studies). Three of the 18 studies reporting choledocholithiasis were excluded from the analysis due to lack of data, or differences in study design. The sensitivity for the 15 studies of choledocholithiasis ranged from 0.50 to 1.00 while specificity ranged from 0.83 to 1.00. The positive likelihood ratio ranged: from 5.44–47.72 and the negative likelihood ratio for the 15 studies ranged from 0.00–0.51. Significant heterogeneity was found across the 15 studies so the sensitivities and specificities were summarised by a Receiver Operating Characteristic (ROC) curve. For malignancy, sensitivity ranged from 0.81 to 0.94 and specificity from 0.92 to 1.00. Positive likelihood ratios ranged from 10.12 to 43 and negative likelihood ratios ranged from 0.15 to 0.21, although these estimates were less reliable. CONCLUSION: MRCP is a comparable diagnostic investigation in comparison to ERCP for diagnosing biliary obstruction

Is group cognitive behaviour therapy for postnatal depression evidence-based practice? A systematic review

Background: There is evidence that psychological therapies including cognitive behaviour therapy (CBT) may be effective in reducing postnatal depression (PND) when offered to individuals. In clinical practice, this is also implemented in a group therapy format, which, although not recommended in guidelines, is seen as a cost-effective alternative. To consider the extent to which group methods can be seen as evidence-based, we systematically review and synthesise the evidence for the efficacy of group CBT compared to currently used packages of care for women with PND, and we discuss further factors which may contribute to clinician confidence in implementing an intervention. Methods: Seventeen electronic databases were searched. All full papers were read by two reviewers and a third reviewer was consulted in the event of a disagreement on inclusion. Selected studies were quality assessed, using the Cochrane Risk of Bias Tool, were data extracted by two reviewers using a standardised data extraction form and statistically synthesised where appropriate using the fixed-effect inverse-variance method. Results: Seven studies met the inclusion criteria. Meta-analyses showed group CBT to be effective in reducing depression compared to routine primary care, usual care or waiting list groups. A pooled effect size of d = 0.57 (95% CI 0.34 to 0.80, p < 0.001) was observed at 10–13 weeks post-randomisation, reducing to d = 0.28 (95% CI 0.03 to 0.53, p = 0.025) at 6 months. The non-randomised comparisons against waiting list controls at 10–13 weeks was associated with a larger effect size of d = 0.94 (95% CI 0.42 to 1.47, p < 0.001). However due to the limitations of the available data, such as ill-specified definitions of the CBT component of the group programmes, these results should be interpreted with caution. Conclusions: Although the evidence available is limited, group CBT was shown to be effective. We argue, therefore, that there is sufficient evidence to implement group CBT, conditional upon routinely collected outcomes being benchmarked against those obtained in trials of individual CBT, and with other important factors such as patient preference, clinical experience, and information from the local context taken into account when making the treatment decision

Nature and reporting characteristics of UK health technology assessment systematic reviews

BACKGROUND: A recent study by Page et al. (PLoS Med. 2016;13(5):e1002028) claimed that increasing numbers of reviews are being published and many are poorly-conducted and reported. The aim of the present study was to assess how well reporting standards of systematic reviews produced in a Health Technology Assessment (HTA) context compare with reporting in Cochrane and other 'non-Cochrane' systematic reviews from the same years (2004 and 2014), as reported by Page et al. (PLoS Med. 2016;13(5):e1002028). METHODS: All relevant UK HTA programme systematic reviews published in 2004 and 2014 were identified. After piloting of the form, two reviewers each extracted relevant data on conduct and reporting from these reviews. These data were compared with data for Cochrane and "non-Cochrane" systematic reviews, as published by Page et al. (PLoS Med. 2016;13(5):e1002028). All data were tabulated and summarized. RESULTS: There were 30 UK HTA programme systematic reviews and 300 other systematic reviews, including Cochrane reviews (n = 45). The percentage of HTA reviews with required elements of conduct and reporting was frequently very similar to Cochrane and much higher than all other systematic reviews, e.g. availability of protocols (90, 98 and 16% respectively); the specification of study design criteria (100, 100, 79%); the reporting of outcomes (100, 100, 78%), quality assessment (100, 100, 70%); the searching of trial registries for unpublished data (70, 62, 19%); reporting of reasons for excluding studies (91, 91 and 70%) and reporting of authors' conflicts of interests (100, 100, 87%). HTA reviews only compared less favourably with Cochrane and other reviews in assessments of publication bias. CONCLUSIONS: UK HTA systematic reviews are often produced within a specific policy-making context. This context has implications for timelines, tools and resources. However, UK HTA systematic reviews still tend to present standards of conduct and reporting equivalent to "gold standard" Cochrane reviews and superior to systematic reviews more generally

Computerised cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: external pilot trial

<p>Abstract</p> <p>Background</p> <p>People with multiple sclerosis (MS) are at high risk of depression. We undertook a pilot trial of computerised cognitive behavioural therapy (CCBT) for the treatment of depression in people with MS to test the feasibility of undertaking a full trial.</p> <p>Methods</p> <p>Participants with a diagnosis of MS and clinical levels of depression were recruited through out-patient clinics and postal screening questionnaires at two UK centres and randomised to CCBT or usual care. Clinical outcomes included the Beck Depression Inventory (BDI-II) and Multiple Sclerosis Impact Scale (MSIS-29) at baseline, 8 and 21 weeks. Feasibility outcomes included: recruitment rate; reasons for refusal, withdrawal and dropout; feasibility and acceptability of the proposed outcome measures; sample size estimation and variation in and preferences for service delivery.</p> <p>Results</p> <p>Twenty-four participants were recruited. The recruitment rate, calculated as the proportion of those invited to fill in a screening questionnaire who were consented into the trial, was 4.1%. Recruitment through out-patient clinics was somewhat slower than through screening questionnaire mail-out but the overall recruitment yield was similar. Of the 12 patients in the CCBT arm, 9 (75%) completed at least four, and 6 completed all 8 CCBT sessions. For completers, the median time (IQR) to complete all eight CCBT sessions was 15 (13 to 20) weeks. Participants expressed concern about the face validity of the Beck Depression Inventory II for the measurement of self-reported depression in people with MS. The MSIS-29 was the patient-reported outcome measure which participants felt best reflected their concerns. The estimated sample size for a full trial is between 180 and 390 participants. NHS partners were not delivering CCBT in community facilities and participants preferred to access CCBT at home, with no one expressing a preference for use of CCBT in an alternative location.</p> <p>Conclusions</p> <p>A definitive trial, with a recruitment window of one year, would require the participation of around 13 MS centres. This number of centres could be reduced by expanding the eligibility criteria to include either other neurological conditions or people with more severe depression. The MSIS-29 should be used as a patient-important outcome measurement.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN81846800">ISRCTN81846800</a></p

Interventions to prevent youth violence in Latin America: a systematic review

Objectives: This review aims to summarise evidence on the effectiveness of interventions to prevent youth violence in Latin America. Methods: A systematic search on 13 academic databases was conducted to locate studies evaluating a primary or secondary prevention intervention in Latin America. Studies could use any type of quantitative design to assess outcomes related to youth violence. A search of websites, references and citation searching was also carried out. The quality of each study was assessed. Results: Nine studies were identified. Most documented positive effects of the interventions on the perception of youth violence present in the community/school. Evidence was found of a reduction in homicides and juvenile crimes in three studies, two of which evaluated a community-based intervention. There were mixed results for the self-report of participation on violent acts. The majority of the studies lacked of a rigorous design. Conclusions: Most of the interventions had some promising results, including the reduction of homicides within communities. Community-based programmes were the most consistent regarding an effectiveness to prevent violence. However, the evidence for Latin America is still scarce and relies on non-rigorously designed studies

The acceptability to patients of computerized cognitive behaviour therapy for depression : a systematic review

Background Cognitive behaviour therapy (CBT) is widely used to treat depression. However, CBT is not always available to patients because of a shortage of therapists and long waiting times. Computerized CBT (CCBT) is one of several alternatives currently available to treat patients with depression. Evidence of its clinical effectiveness has led to programs being used increasingly within the UK and elsewhere. However, little information is available regarding the acceptability of CCBT to patients. Method A systematic review of sources of information on acceptability to patients of CCBT for depression. Results Sources of information on acceptability included: recruitment rates, patient drop-outs and patient-completed questionnaires. We identified 16 studies of CCBT for the treatment of depression that provided at least some information on these sources. Limited information was provided on patient take-up rates and recruitment methods. Drop-out rates were comparable to other forms of treatment. Take-up rates, when reported, were much lower. Six of the 16 studies included specific questions on patient acceptability or satisfaction although information was only provided for those who had completed treatment. Several studies have reported positive expectancies and high satisfaction in routine care CCBT services for those completing treatment. Conclusions Trials of CCBT should include more detailed information on patient recruitment methods, drop-out rates and reasons for dropping out. It is important that well-designed surveys and qualitative studies are included alongside trials to determine levels and determinants of patient acceptability

Tramadol for premature ejaculation: A systematic review and meta-analysis Sexual function and fertility

Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in breathing and the beneficial effect of tramadol in PE is yet not supported by a high level of evidence. The purpose of this study was to systematically review the evidence from randomised controlled trials (RCT) for tramadol in the management of PE. Methods: We searched bibliographic databases including MEDLINE to August 2014 for RCTs. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. Between-group differences in IELT and other outcomes were pooled across RCTs in a meta-analysis. Statistical and clinical between-trial heterogeneity was assessed. Results: A total of eight RCTs that evaluated tramadol against a comparator were included. The majority of RCTs were of unclear methodological quality due to limited reporting. Pooled evidence (four RCTs, 721 participants), suggests that tramadol is significantly more effective than placebo at increasing IELT over eight to 12 weeks (p = 0.0007). However, a high level of statistical heterogeneity is evident (I-squared = 74%). Single RCT evidence indicates that tramadol is significantly more effective than paroxetine taken on-demand, sildenafil, lidocaine gel, or behavioural therapy on IELT in men with PE. Tramadol is associated with significantly more adverse events including: erectile dysfunction, constipation, nausea, headache, somnolence, dry mouth, dizziness, pruritus, and vomiting, than placebo or behavioural therapy over eight to 12 weeks of treatment. However, addiction problems or breathing difficulties reported by patients for PE is not assessed in the current evidence base. Conclusions: Tramadol appears effective in the treatment of PE. However, these findings should be interpreted with caution given the observed levels of between-trial heterogeneity and the reporting quality of the available evidence. The variability across placebo-controlled trials in terms of the tramadol dose evaluated and the treatment duration does not permit any assessment of a safe and effective minimum daily dose. The long-term effects and side effects, including addiction potential, for men with PE have not been evaluated in the current evidence base. Trial registration: The review is registered on PROSPERO 2013: CRD42013005289

Sexual health risk reduction interventions for people with severe mental illness: a systematic review

Background Despite variability in sexual activity among people with severe mental illness, high-risk sexual behavior (e.g. unprotected intercourse, multiple partners, sex trade and illicit drug use) is common. Sexual health risk reduction interventions (such as educational and behavioral interventions, motivational exercises, counselling and service delivery), developed and implemented for people with severe mental illness, may improve participants’ knowledge, attitudes, beliefs behaviors or practices (including assertiveness skills) and could lead to a reduction in risky sexual behavior. This systematic review evaluates the effectiveness of sexual health risk reduction interventions for people with severe mental illness. Methods Thirteen electronic databases (including MEDLINE, EMBASE and PsycINFO) were searched to August 2014, and supplemented by hand-searching relevant articles and contacting experts. All controlled trials (randomized or non-randomized) comparing the effectiveness of sexual health risk reduction interventions with usual care for individuals living in the community with severe mental illness were included. Outcomes included a range of biological, behavioral and proxy endpoints. Narrative synthesis was used to combine the evidence. Results Thirteen controlled trials (all from the USA) were included. Although there was no clear and consistent evidence that interventions reduce the total number of sex partners or improved behavioral intentions in sexual risk behavior, positive effects were generally observed in condom use, condom protected intercourse and on measures of HIV knowledge, attitudes to condom use and sexual behaviors and practices. However, the robustness of these findings is low due to the large between study variability, small sample sizes and low-to-moderate quality of included studies. Conclusions There is insufficient evidence at present to fully support or reject the identified sexual health risk reduction interventions for people with severe mental illness. Given the serious consequences of high-risk sexual behaviors, there is an urgent need for well-designed UK based trials, as well as training and support for staff implementing sexual health risk reduction interventions