You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials
Abstract 1:
The efficacy and safety of lisdexamfetamine dimesylate ( LDX ) vs placebo in binge eating disorder ( BED ) was evaluated in two multicenter , double-blind , placebo-controlled trials . Adults ( study 1 , n=383 ; study 2 , n=390 ) meeting DSM-IV-TR BED criteria were r and omized ( 1:1 ) to  placebo  or LDX ( 50 or 70 mg/day ) dose titration ; optimized doses were maintained to the end of double-blind treatment ( week 12/early termination ) . Change from baseline in binge eating days/week at weeks 11−12 ( primary efficacy endpoint ) was assessed with mixed-effects models for repeated measures . Secondary endpoints related to binge eating and medical parameters , safety , and treatment compliance were also assessed . Least squares mean ( 95 % CI ) treatment differences for change from baseline binge eating days/week at weeks 11–12 significantly favored LDX ( study 1 : –1.35 [ –1.70 , –1.01 ] ; study 2 : –1.66 [ –2.04 , –1.28 ] ; both P<0.001 ) . In both studies , treatment-emergent adverse events ( TEAEs ) reported by ⩾10 % of LDX participants were dry mouth , insomnia , and headache . Serious TEAEs occurred in two ( 1.1 % ) placebo participants in each study and in three ( 1.6 % ) and one ( 0.6 % ) LDX participants in study 1 and study 2 , respectively . Across studies , mean increases from baseline at week 12/early termination with LDX for pulse and systolic and diastolic blood pressure ranged from 4.41–6.31 b.p.m . and 0.2–1.45 and 1.06–1.83 mm Hg , respectively . LDX ( 50 and 70 mg/day ) was superior to placebo in decreasing binge eating days/week from baseline and improving binge eating – related key secondary endpoints . Safety results appear consistent with the known safety profile of LDX


Title 2:
The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
Abstract 2:
Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more


Title 3:
The Cost Effectiveness of Lisdexamfetamine Dimesylate for the Treatment of Binge Eating Disorder in the USA
Abstract 3:
Background Lisdexamfetamine dimesylate ( LDX ) demonstrated efficacy in terms of reduced binge eating days per week in adults with binge eating disorder ( BED ) in two r and omized clinical trials ( RCTs ) . Objective The objective of this study was to evaluate the cost effectiveness of LDX versus no pharmacotherapy ( NPT ) in adults with BED from a USA healthcare payer ’s perspective . Study Design and Methods A decision-analytic Markov cohort model was developed using 1-week cycles and a 52-week time horizon . Markov health states were defined based upon the Diagnostic and Statistical Manual of Mental Disorders , 5th Edition criteria of BED . Model parameter estimates were obtained from RCTs , a survey , and literature . The primary outcome was incremental cost-effectiveness ratio ( ICER ) . The analysis assumed a 12-week course of treatment , based upon RCTs ’ treatment duration . One-way deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results . Results Patients on LDX therapy gained 0.006 quality -adjusted life years ( QALY ) compared to patients on the NPT arm , while the average total cost was US$ 175 higher for LDX therapy . The estimated ICER  for LDX compared with NPT was US$ 27,618 per QALY , which was shown to be cost effective given a willingness-to-pay threshold of US$ 50,000 . Conclusions Treatment of BED with LDX showed increase in QALYs at an acceptable cost and is considered to be cost effective at the commonly used willingness-to-pay threshold in the USA . Based on the available evidence , the current model focused on short-term benefits only . There is a need to generate additional scientific evidence supporting long-term benefits of LDX therapy for BED


Title 4:
Validation of the yale-brown obsessive compulsive scale modified for binge eating.
Abstract 4:
OBJECTIVE Establish the Yale-Brown obsessive compulsive scale modified for binge eating ( YBOCS-BE ) as a fit for purpose measure of treatment benefit in clinical trials of binge eating disorder ( BED ) . METHODS YBOCS-BE psychometric properties were evaluated with data from a Phase 2 r and omized controlled trial of lisdexamfetamine dimesylate in 260 adults with BED . Assessment s included : Cohen 's effect size estimates of item-level sensitivity and scale-level external responsiveness ; item-to-total correlations ; Cronbach 's alpha for internal consistency reliability ; Spearman correlations against reference measures for construct validity ; known-groups analyses for discriminating ability ; t tests of within-group differences between baseline and post baseline visits for internal responsiveness ; and multiple anchor-based approaches to estimate minimum clinical ly important change ( MCIC ) . RESULTS No significant distribution anomalies were seen . Items appear sensitive to treatment group differences . Item-to-total correlations were positive . Internal consistency is 0.81 . Large correlations ( > 0.50 ) were seen between YBOCS-BE score change and the Clinical Global Impression-Improvement ( CGI-I ; 0.58 ) and score changes for the following ; number of binge days ( 0.38 ) , Clinical Global Impression-Severity ( CGI-S ; 0.57 ) , the disinhibition ( 0.57 ) and hunger ( 0.52 ) subscales of the Three-Factor Eating Question naire ( TFEQ ) , and the Barratt Impulsiveness Scale ( BIS-11 ; 0.58 ) . MCIC estimates range from -4 to -17 . DISCUSSION The YBOCS-BE was found to be a reliable and valid measure of an important and unique concept in BED-related clinical studies . Study limitations include using protocol -defined BED severity level and the exclusion of psychiatric comorbidities


Title 5:
Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial.
Abstract 5:
IMPORTANCE  Binge-eating disorder ( BED ) , a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome , lacks approved pharmacotherapies . OBJECTIVE To examine the efficacy and safety of lisdexamfetamine dimesylate , a dextroamphetamine prodrug , to treat moderate to severe BED . DESIGN , SETTING , AND PARTICIPANTS We performed a r and omized , double-blind , parallel-group , forced dose titration , placebo-controlled clinical trial at 30 sites from May 10 , 2011 , through January 30 , 2012 . Safety and intention-to-treat analyses included 259 and 255 adults with BED , respectively . INTERVENTIONS Lisdexamfetamine dimesylate at dosages of 30 , 50 , or 70 mg/d or placebo were provided to study participants ( 1:1:1:1 ) . Dosages were titrated across 3 weeks and maintained for 8 weeks . We followed up participants for a mean ( SD ) of 7 ( 2 ) days after the last dose . MAIN OUTCOMES AND MEASURES We assessed the change in binge-eating ( BE ) behaviors measured as days per week ( baseline to week 11 ) with a mixed-effects model using transformed log ( BE days per week ) + 1 . Secondary measures included BE cessation for 4 weeks . Safety assessment s included treatment-emergent adverse events , vital signs , and change in weight . RESULTS At week 11 , log-transformed BE days per week decreased with the 50-mg/d ( least squares [ LS ] mean [ SE ] change , -1.49 [ 0.066 ] ; P = .008 ) and 70-mg/d ( LS mean [ SE ] change , -1.57 [ 0.067 ] ; P < .001 ) treatment groups but not the 30-mg/d treatment group ( LS mean [ SE ] change , -1.24 [ 0.067 ] ; P = .88 ) compared with the placebo group . Nontransformed mean ( SD ) days per week decreased for placebo and the 30- , 50- , and 70-mg/d treatment groups by -3.3 ( 2.04 ) , -3.5 ( 1.95 ) , -4.1 ( 1.52 ) , and -4.1 ( 1.57 ) , respectively . The percentage of participants achieving 4-week BE cessation was lower with the placebo group ( 21.3 % ) compared with the 50-mg/d ( 42.2 % [ P = .01 ] ) and 70-mg/d ( 50.0 % [ P < .001 ] ) treatment groups . The incidence of any treatment-emergent adverse events was 58.7 % for the placebo group and 84.7 % for the combined treatment group . In the treatment groups , 1.5 % of participants had serious treatment-emergent adverse effects . Events with a frequency of at least 5 % and changes in heart rate were generally consistent with the known safety profile . The mean ( SD ) change in body weight was -0.1 ( 3.09 ) , -3.1 ( 3.64 ) , -4.9 ( 4.43 ) , -4.9 ( 3.93 ) , and -4.3 ( 4.09 ) kg for the placebo group , the 30- , 50- , and 70-mg/d treatment groups , and the combined treatment groups , respectively ( P < .001 for each dose vs placebo group comparison in post hoc analysis ) . CONCLUSIONS AND RELEVANCE The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days , BE cessation , and global improvement . The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder . Further investigation of lisdexamfetamine in BED is ongoing . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01291173
Across the included acute phase RCTs , lisdexamfetamine ( at 30 , 50 , or 70 mg/day ) led to significant reduction in a number of clinical ly relevant outcomes compared to placebo .