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Objective: The Cochrane Handbook of Systematic Reviews contains search filters to find randomized controlled trials (RCTs) in Ovid MEDLINE: one maximizing sensitivity and another balancing sensitivity and precision. These filters were originally published in 1994 and were adapted and updated in 2008. To determine the performance of these filters, the authors tested them and thirty-six other MEDLINE filters against a large new gold standard set of relevant records.Methods: We identified a gold standard set of RCT reports published in 2016 from the Cochrane CENTRAL database of controlled clinical trials. We retrieved the records in Ovid MEDLINE and combined these with each RCT filter. We calculated their sensitivity, relative precision, and f-scores.Results: The gold standard comprised 27,617 records. MEDLINE searches were run on July 16, 2019. The most sensitive RCT filter was Duggan et al. (sensitivity=0.99). The Cochrane sensitivity-maximizing RCT filter had a sensitivity of 0.96 but was more precise than Duggan et al. (0.14 compared to 0.04 for Duggan). The most precise RCT filters had 0.97 relative precision and 0.83 sensitivity.Conclusions: The Cochrane Ovid MEDLINE sensitivity-maximizing RCT filter can continue to be used by Cochrane reviewers and to populate CENTRAL, as it has very high sensitivity and a slightly better precision relative to more sensitive filters. The results of this study, which used a very large gold standard to compare the performance of all known RCT filters, allows searchers to make better informed decisions about which filters to use for their work.

Purpose Health state utility values are commonly used to inform economic evaluations and determine the cost-effectiveness of an intervention. The aim of this systematic review is to summarise the utility values available to represent the health-related quality of life (HRQoL) of patients with thyroid cancer. Methods Eight electronic databases were searched from January 1999 to April 2019 for studies which included assessment of HRQoL for patients with thyroid cancer. Utility estimates derived from multiple sources (EuroQol questionnaire 5-dimension (EQ-5D), time trade-off [TTO] and standard gamble [SG] methods) were extracted. In addition, utility estimates were generated by mapping from SF-36 and EORTC QLQ-30 to the EQ-5D-3L UK value set using published mapping algorithms. Results Searches identified 33 eligible studies. Twenty-six studies reported HRQoL for patients with differentiated thyroid cancer and seven studies for patients with general thyroid cancer. We identified studies which used different methods and tools to quantify the HRQoL in patients with thyroid cancer, such as the EQ-5D-3L, SF-36, EORTC QLQ-30 and SG and TTO techniques to estimate utility values. Utility estimates range from 0.205 (patients with low-risk differentiated thyroid cancer) to utility values approximate to the average UK population (following successful thyroidectomy surgery and radioiodine treatment). Utility estimates for different health states, across thyroid cancer sub-types and interventions are presented. Conclusion A catalogue of utility values is provided for use when carrying out economic modelling of thyroid cancer; by including mapped values, this approach broadens the scope of health states that can be considered within cost-effectiveness modelling.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can detect AF at a single-time point. To assess the diagnostic test accuracy, clinical impact and cost effectiveness of single-time point lead-I ECG devices compared with manual pulse palpation (MPP) followed by a 12-lead ECG for the detection of AF in symptomatic primary care patients with an irregular pulse. Electronic databases (MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process, EMBASE, PubMed and Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database) were searched to March 2018. Two reviewers screened the search results, extracted data and assessed study quality. Summary estimates of diagnostic accuracy were calculated using bivariate models. Cost-effectiveness was evaluated using an economic model consisting of a decision tree and two cohort Markov models. Diagnostic accuracy The diagnostic accuracy (13 publications reporting on nine studies) and clinical impact (24 publications reporting on 19 studies) results are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% (95% confidence interval [CI]: 86.2% to 97.4%) and summary specificity was 96.5% (95% CI: 90.4% to 98.8%). Cost effectiveness The de novo economic model yielded incremental cost effectiveness ratios (ICERs) per quality adjusted life year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generate ICERs per QALY gained below the £20,000-£30,000 threshold. Kardia Mobile is the most cost effective option in a full incremental analysis. Lead-I ECG tests may identify more AF cases than the standard diagnostic pathway. This comes at a higher cost but with greater patient benefit in terms of mortality and quality of life. No published data evaluating the diagnostic accuracy, clinical impact or cost effectiveness of lead-I ECG devices for the target population are available. The use of single-time point lead-I ECG devices in primary care for the detection of AF in people with signs or symptoms of AF and an irregular pulse appears to be a cost effective use of NHS resources compared with MPP followed by a 12-lead ECG, given the assumptions used in the base case model. The protocol for this review is registered on PROSPERO as CRD42018090375.

Background This work aimed to identify studies of interventions seeking to address mental health inequalities, studies assessing the economic impact of such interventions and factors which act as barriers and those that can facilitate interventions to address inequalities in mental health care. Methods A systematic mapping method was chosen. Studies were included if they: (1) focused on a population with: (a) mental health disorders, (b) protected or other characteristics putting them at risk of experiencing mental health inequalities; (2) addressed an intervention focused on addressing mental health inequalities; and (3) met criteria for one or more of three research questions: (i) primary research studies (any study design) or systematic reviews reporting effectiveness findings for an intervention or interventions, (ii) studies reporting economic evaluation findings, (iii) primary research studies (any study design) or systematic reviews identifying or describing, potential barriers or facilitators to interventions. A bibliographic search of MEDLINE, HMIC, ASSIA, Social Policy & Practice, Sociological Abstracts, Social Services Abstracts and PsycINFO spanned January 2008 to December 2018. Study selection was performed according to inclusion criteria. Data were extracted and tabulated to map studies and summarise published research on mental health inequalities. A visual representation of the mapping review (a mapping diagram) is included. Results Overall, 128 studies met inclusion criteria: 115 primary studies and 13 systematic reviews. Of those, 94 looked at interventions, 6 at cost-effectiveness and 36 at barriers and facilitators. An existing taxonomy of disparities interventions was used and modified to categorise interventions by type and strategy. Most of the identified interventions focused on addressing socioeconomic factors, race disparities and age-related issues. The most frequently used intervention strategy was providing psychological support. Barriers and associated facilitators were categorised into groups including (not limited to) access to care, communication issues and financial constraints. Conclusions The mapping review was useful in assessing the spread of literature and identifying highly researched areas versus prominent gaps. The findings are useful for clinicians, commissioners and service providers seeking to understand strategies to support the advancement of mental health equality for different populations and could be used to inform further research and support local decision-making. Systematic review registration Not applicable.

IntroductionThe Cochrane Handbook of Systematic Reviews contains two search filters to find randomized controlled trials (RCT) in Ovid MEDLINE: a sensitivity maximizing RCT filter and a sensitivity and precision maximizing RCT filter. The RCT search strategies were originally published in 1994 have been adapted and updated, most recently in 2008. To determine whether the Cochrane filters are still performing adequately to inform Cochrane reviews, we tested the performance of the Cochrane filters and 36 other MEDLINE filters in a large new gold standard set of relevant records.MethodsWe identified a gold standard set of RCT reports published in 2016 from the Cochrane CENTRAL database of controlled clinical trials. We retrieved the records in Ovid MEDLINE using their PubMed identifiers. Each RCT filter was run in MEDLINE and combined with the gold standard set of records, to determine their sensitivity, precision and f-scores.ResultsThe gold standard comprised 27,617 records and the searches were run on 16 July 2019. The most sensitive RCT filter was Duggan (sensitivity 0.99). The Cochrane sensitivity maximizing RCT filter had a sensitivity of 0.96, but was more precise than Duggan (0.14 compared to 0.04 for Duggan). The most precise RCT filter was Chow, Glanville/Lefebvre, Royle/Waugh, Dumbrique (precision 0.97, sensitivity 0.83). The best precision Cochrane filter was the sensitivity and precision maximising RCT filter.ConclusionsThe Cochrane MEDLINE sensitivity maximizing RCT filter can continue to be used by Cochrane reviewers and CENTRAL compilers as it has very high sensitivity but a more acceptable precision than many higher sensitivity filters. Slightly more sensitive filters are available, but with lower precision than the Cochrane sensitivity maximizing RCT filter. These other filters may be preferred when combining with a subject search when record numbers may be more manageable than searching the whole of MEDLINE.

ObjectivesThe aim of this review was to identify the cultural, social, structural and behavioural factors that influence asymptomatic breast and cervical cancer screening attendance in South Asian populations, in order to improve uptake and propose priorities for further research.DesignA systematic review of the literature for inductive, comparative, prospective and intervention studies. We searched the following databases: MEDLINE/In-Process, Web of Science, EMBASE, SCOPUS, CENTRAL, CDSR, CINAHL, PsycINFO and PsycARTICLES from database inception to 23 January 2018. The review included studies on the cultural, social, structural and behavioural factors that influence asymptomatic breast and cervical cancer screening attendance and cervical smear testing (Papanicolaou test) in South Asian populations and those published in the English language. The framework analysis method was used and themes were drawn out following the thematic analysis method.SettingsAsymptomatic breast or cervical screening.ParticipantsSouth Asian women, including Bangladeshi, Indian, Pakistani, Sri Lankan, Bhutanese, Maldivian and Nepali populations.Results51 included studies were published between 1991 and 2018. Sample sizes ranged from 25 to 38 733 and participants had a mean age of 18 to 83 years. Our review showed that South Asian women generally had lower screening rates than host country women. South Asian women had poorer knowledge of cancer and cancer prevention and experienced more barriers to screening. Cultural practices and assumptions influenced understandings of cancer and prevention, emphasising the importance of host country cultures and healthcare systems.ConclusionsHigh-quality research on screening attendance is required using prospective designs, where objectively validated attendance is predicted from cultural understandings, beliefs, norms and practices, thus informing policy on targeting relevant public health messages to the South Asian communities about screening for cancer.PROSPERO registration numberCSD 42015025284.

As part of the single technology appraisal process, the National Institute for Health and Care Excellence invited Merck to submit evidence for the clinical and cost effectiveness of cladribine tablets (cladribine) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Rapidly evolving severe (RES) and sub-optimally treated (SOT) RRMS were specified by the National Institute for Health and Care Excellence as subgroups of interest. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group. This article summarises the Evidence Review Group’s review of the company’s evidence submission for cladribine and the Appraisal Committee’s final decision. The final scope issued by the National Institute for Health and Care Excellence listed the following disease-modifying treatments as comparators: alemtuzumab, daclizumab, fingolimod and natalizumab. At the time of the company submission, a licence was anticipated for low-dose cladribine. The main clinical evidence (the CLARITY trial) in the company submission focused on the efficacy of low-dose cladribine vs. placebo. The CLARITY trial showed a statistically significant reduction in relapse rate for cladribine in the RES-RRMS subgroup ( n  = 50) but not in the SOT-RRMS subgroup ( n  = 19). Cladribine showed a numerical, but not a statistically significant, advantage in delaying disability progression at 6 months in the RES-RRMS subgroup. Disability progression benefits could not be estimated for those in the SOT-RRMS subgroup because of few events. The Evidence Review Group’s main concern regarding the clinical evidence was the small sample size of the subgroups. To compare the effectiveness of cladribine to other disease-modifying treatments, the company conducted network meta-analyses, which showed cladribine and its comparators to be equally effective. The Evidence Review Group considered the results of the disease-modifying treatments to be unreliable because few trials were in the network. The company’s cost-effectiveness evidence showed cladribine to be cheaper and more effective than other disease-modifying treatments in the RES-RRMS arm and the SOT-RRMS arm. The results were most sensitive to treatment effect on disability progression at 6 months. The Evidence Review Group was concerned that there was insufficient evidence to conclude that cladribine was superior to placebo in delaying disability progression. The Evidence Review Group amended the company’s economic model to allow alternative estimates for the treatment effect of cladribine and its comparators on relapse rate and disability progression at 6 months. The Evidence Review Group made other changes to the company model. After implementing all the amendments, cladribine remained cost effective in the RES-RRMS and SOT-RRMS subgroups. The Appraisal Committee recognised the uncertainty in the available data but concluded that cladribine could be considered a cost-effective use of National Health Service resources.

As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE’s 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG’s review of the company’s evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG’s main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG’s amendments to the company’s cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company’s base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company’s base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000–£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem.

As part of the Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of cenegermin (OXERVATE ® , Dompé) to submit evidence for the clinical and cost effectiveness of cenegermin for neurotrophic keratitis (NK). The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG’s review of the evidence submitted by the company and provides a summary of the Appraisal Committee’s (AC) final decision. Clinical-effectiveness evidence from two phase II randomised controlled trials (RCTs) of cenegermin found cenegermin to improve corneal healing after 8 weeks compared with vehicle, considered a proxy for artificial tears. Longer-term data and comparisons with other relevant comparators were insufficient to draw conclusions. The company developed a de novo economic model that found cenegermin to be dominant when compared with artificial tears, except in one of seven scenarios. However, the ERG considered that the model had a major structural flaw in that it failed to allow patients to enter a ‘sustained healing’ state from ‘standard of care (SoC) non-healing’ and ‘SoC deteriorating’ states, or to move into an ‘SoC deteriorating’ state from an ‘SoC non-healing’ state. Following the first AC meeting, the company submitted a revised model with a revised model structure that removed the ‘SoC deteriorating’ state and introduced an ‘SoC healed’ state to sit alongside the existing ‘sustained healing’ and ‘SoC non-healing’ states from the original model. However, the ERG continued to express concerns, which included (1) extrapolation of the treatment effect of cenegermin over a patient’s lifetime; (2) the assumption that patients had two specialist visits a month; (3) the assumption that artificial tears, autologous serum eye drops and contact lenses continued for a lifetime after healing; (4) the simplified modelling of costs and utilities; and (5) the underlying uncertainty in the utility values. The ERG therefore considered the company’s model could not produce a robust incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. The ERG did however present an alternative ICER by amending the use and cost of autologous serum eye drops, contact lenses and artificial tears in the ‘healed’ and ‘non-healed’ states. Applying these changes produced an ICER of £302,717 per QALY gained. Because of uncertainties with the clinical- and cost-effectiveness evidence, the AC concluded that cenegermin cannot be recommended within its marketing authorisation for NK.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Shire Pharmaceuticals) of pegylated liposomal irinotecan hydrochloride trihydrate (liposomal irinotecan) to submit clinical and cost-effectiveness evidence for its use in combination with 5-fluorouracil (5-FU) and folic acid/leucovorin (LV) for treating patients with pancreatic cancer following prior treatment with gemcitabine as part of the institute’s Single Technology Appraisal process. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company’s evidence, the ERG review and the resulting NICE guidance (TA440), issued on 26 April 2017. Clinical evidence for liposomal irinotecan + 5-FU/LV versus 5-FU/LV was derived from 236 patients with metastatic pancreatic cancer in the multinational, open-label, randomised controlled NAPOLI-1 trial. Results from analyses of progression-free survival and overall survival showed statistically significant improvements for patients treated with liposomal irinotecan + 5-FU/LV compared with those treated with 5-FU/LV. However, 5-FU/LV alone is rarely used in National Health Service clinical practice for patients with metastatic pancreatic cancer previously treated with gemcitabine. The company, ERG and Appraisal Committee (AC) all agreed that oxaliplatin + 5-FU/LV is the most commonly used treatment. Oxaliplatin + 5-FU/LV was compared with 5-FU/LV in two trials identified by the company. However, the company and the ERG both considered attempts to compare the efficacy of liposomal irinotecan + 5-FU/LV with oxaliplatin + 5-FU/LV to be methodologically flawed; not only was there heterogeneity between trials and their populations but also the proportional hazards assumption required to conduct a robust indirect treatment comparison (ITC) was violated. Nonetheless, data derived from an ITC were used to inform the company’s economic model. Using the discounted patient access scheme price for liposomal irinotecan + 5-FU/LV, the company reported an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £54,412 for the comparison with oxaliplatin + 5-FU/LV. The ERG considered that the company’s base-case cost-effectiveness results for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV were underestimates and should be interpreted with extreme caution. Following implementation of a number of model amendments, the ERG’s modified exploratory ICER for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV was £106,898 per QALY gained. The AC accepted the majority of the ERG’s amendments to the model, and also highlighted that the total QALYs for oxaliplatin + 5-FU/LV were lower than for 5-FU/LV in the company’s model, which the AC considered to be clinically implausible. The AC therefore considered results from exploratory analyses, undertaken by the ERG, which included altering the QALY difference between liposomal irinotecan + 5-FU/LV and oxaliplatin + 5-FU/LV by ± 10%. These analyses resulted in ICERs for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV of between £201,019 per QALY gained to liposomal irinotecan + 5-FU/LV being dominated by oxaliplatin + 5-FU/LV. Therefore, despite uncertainty around the clinical-effectiveness evidence and cost-effectiveness results, the AC was confident that the ICER was in excess of £50,000 per QALY gained. The final guidance issued by NICE is that liposomal irinotecan + 5-FU/LV is not recommended within its marketing authorisation for treating metastatic adenocarcinoma of the pancreas in adults whose disease has progressed after gemcitabine-based therapy.