Innovations in infertility: a comprehensive analysis of the ClinicalTrials.gov database.

OBJECTIVE: To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion. DESIGN: Retrospective review of trials registered with ClinicalTrials.gov. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Descriptive statistics characterizing the attributes of the clinical trials including intervention type, topic, population, completion status, size, location, sponsor, and results. The effects of the sponsor and trial location on trial noncompletion were assessed via logistic regression. RESULT(S): In total, 505 trials initiated between 2010 and 2020 were included in our analysis. Drug interventions were the most commonly studied (45%); ovarian stimulation trials accounted for 27% of the studies. Live birth was tracked as an outcome by 20% of the studies; 3% of the trials included mental health outcomes. Few trials (15%) enrolled male participants. Only 11% of the trials reported results, and 4% of the trials reported the race or ethnicity of the participants. Most trials (82%) were conducted outside the United States. Overall, 18% of the trials were not completed, most often because of lack of accrual (47%). United States trials had over twice the odds of noncompletion in univariate analysis (odds ratio = 2.48, 95% confidence interval = [1.47, 4.17]); however, this relationship lost significance after adjusting for potential confounders (odds ratio = 0.95, 95% confidence interval = [0.42, 2.14]). Trial sponsorship was not associated with trial noncompletion. CONCLUSION(S): Infertility trials predominantly investigated drug interventions, particularly ovarian stimulation. Live birth was an infrequent outcome despite its relevance to patients. Clinical trials should aim to address the unmet needs in fertility care and be inclusive of underserved populations affected by infertility.

Impact of interoperability of smart infusion pumps and an electronic medical record in critical care.

PURPOSE: To describe the benefits of smart infusion pump interoperability with an electronic medical record (EMR) system in an adult intensive care unit (ICU) setting. SUMMARY: In order to assess the impact of smart infusion pump and EMR interoperability, we observed whether there were changes in the frequency of electronic medication administration record (eMAR) documentation of dose titrations in epinephrine and norepinephrine infusions in the ICU setting. As a secondary endpoint, we examined whether smart pump/EMR interoperability had any impact on the rate of alerts triggered by the dose-error reduction software. Pharmacist satisfaction was measured to determine the impact of smart pump/EMR interoperability on pharmacist workflow. In the preimplementation phase, there were a total of 2,503 administrations of epinephrine and norepinephrine; 13,299 rate changes were documented, for an average of 5.31 documented rate changes per administration. With smart pump interoperability, a total of 13,024 rate changes were documented in association with 1,401 administrations, for an average of 9.29 documented rate changes per administration (a 74.9% increase). A total of 1,526 dose alerts were triggered in association with 76,145 infusions in the preimplementation phase; there were 820 dose alerts associated with 48,758 autoprogammed infusions in the postimplementation phase (absolute difference, -0.32%). ICU pharmacists largely agreed (75% of survey respondents) that the technology provided incremental value in providing patient care. CONCLUSION: Interoperability between the smart pump and EMR systems proved beneficial in the administration and monitoring of continuous infusions in the ICU setting. Additionally, ICU pharmacists may be positively impacted by improved clinical data accuracy and operational efficiency.

Facilitating Longitudinal Exposure-Response Modeling of a Composite Endpoint Using the Joint Modeling of Sparsely and Frequently Collected Subcomponents.

Longitudinal exposure-response modeling plays an important role in optimizing dose and dosing regimens in clinical drug development. Certain clinical trials contain induction and maintenance phases where the maintenance treatment depends on the subjects' achieving the main endpoint outcome in the induction phase. Due to logistic difficulties and cost considerations, the main endpoint is usually collected more sparsely than a subcomponent (or other related endpoints). The sparse collection of the main endpoint hampers its longitudinal modeling. In principle, the frequent collection of a subcomponent allows its longitudinal modeling. However, the model evaluation via the visual predictive check (VPC) in the maintenance phase is difficult due to the requirement of the main-endpoint model to identify the treatment subgroups. This manuscript proposes a solution to this dilemma via the joint modeling of the main endpoint and the subcomponent. The challenges are illustrated by analyzing the data collected up to 60 weeks from a phase III trial of ustekinumab in patients with moderate-to-severe ulcerative colitis (UC). The main endpoint Mayo score, a commonly used composite endpoint to measure the severity of UC, was collected only at baseline, the end of the induction phase, and the end of the maintenance phase. The partial Mayo score, which is a major subset of the Mayo score, was collected at nearly every 4 weeks. A longitudinal joint exposure-response model, developed under a latent-variable Indirect Response modeling framework, described the Mayo score time course and facilitated the VPC model evaluation under a response-adaptive trial design.

Determine what to measure and how to measure in clinical trials for the treatment of pressure injury: A protocol for the development of a core outcome set.

BACKGROUND: A core outcome set (COS) is an agreed minimum set of outcomes that should be reported in all clinical trials in specific areas of health care. A considerable amount of trials did not report essential outcomes or outcomes measurement methods, which makes it challenging to evaluate the efficacy and safety of treatment strategies for pressure injury (PI) and produced significant heterogeneity of reported outcomes. It is necessary to develop a COS, which can be used for clinical trials in PI treatment. METHODS/DESIGN: The development of this COS will be guided by an advisory group composed of clinicians, senior nurses, patients, and methodologists. We will search six databases and 2 registry platforms to identify currently reported PI treatment outcomes and outcome measurement instruments in randomized controlled trials, meta-analysis, and systematic reviews. We will also conduct a semi-structured interview with clinicians, nurses, and adult PI patients to collect their opinions on important outcomes. Each outcome of the initial list generated from systematic review and interviews will be scored and reach a consensus through two rounds of international Delphi survey with all key stakeholders. A face-to-face consensus meeting with key stakeholders will be conducted to finish a final COS and recommend measurement instruments for each outcome. RESULTS: We will develop a COS that should be reported in future clinical trials to evaluate the effectiveness of PI treatment. DISCUSSION: The COS will follow current guidance to develop a high-quality COS in the field of PI treatment to reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies, and improve the quality of clinical trials.

Evolving primary and secondary endpoints in randomized controlled trials leading to approval of biologics and small molecules in IBD: an historical perspective.

Introduction: Therapeutic goals in inflammatory bowel diseases (IBD) have evolved, over the last decades, from clinical response to complete remission (clinical and endoscopic remission).Areas covered: Development of biologics and small molecules has been associated with the development of new endpoints in IBD trials that could not have been achieved in the pre-biologics era. Herein, we focus on evolving endpoints for approved biologics and small molecules. We searched for relevant publications using Medline/PubMed, Embase and the Cochrane Library from their inception to 1 July 2019.Expert opinion: Endpoints differ between induction (clinical and endoscopic response) and maintenance trials (clinical and endoscopic remission) because the goal is to evaluate the anti-inflammatory effect of a given drug during induction, whereas full disease control is the ultimate goal during the maintenance phase in order to change patients' life and disease course. Histological healing has recently emerged as a new co-primary endpoint in ulcerative colitis, and is now part of the definition of mucosal healing in these trials. Whether new endpoints such as transmural and radiologic healing could become an endpoint and replace endoscopy in Crohn's disease trials in the near future requires further investigation.

Beyond Randomized Clinical Trials: Use of External Controls.

Randomized controlled trials are the gold standard to investigate efficacy and safety of new treatments. In certain settings, however, randomizing patients to control may be difficult for ethical or feasibility reasons. Borrowing strength using relevant individual patient data on control from external trials or real-world data (RWD) sources may then allow us to reduce, or even eliminate, the concurrent control group. Naive direct use of external control data is not valid due to differences in patient characteristics and other confounding factors. Instead, we suggest the rigorous application of meta-analytic and propensity score methods to use external controls in a principled way. We illustrate these methods with two case studies: (i) a single-arm trial in a rare cancer disease, using propensity score matching to construct an external control from RWD; (ii) a randomized trial in children with multiple sclerosis, borrowing strength from past trials using a Bayesian meta-analytic approach.

A pragmatic approach to intravenous anaesthetics and electroencephalographic endpoints for the treatment of refractory and super-refractory status epilepticus in critical care.

Status epilepticus is a common neurological emergency, with overall mortality around 20%. Over half of cases are first time presentations of seizures. The pathological process by which spontaneous seizures are generated arises from an imbalance in excitatory and inhibitory neuronal networks, which if unchecked, can result in alterations in intracellular signalling pathways and electrolyte shifts, which bring about changes in the blood brain barrier, neuronal cell death and eventually cerebral atrophy. This narrative review focusses on the treatment of status epilepticus in adults. Anaesthetic agents interrupt neuronal activity by enhancing inhibitory or decreasing excitatory transmission, primarily via GABA and NMDA receptors. Intravenous anaesthetic agents are commonly used as second or third line drugs in the treatment of refractory status epilepticus, but the optimal timing and choice of anaesthetic drug has not yet been established by high quality evidence. Titration of antiepileptic and anaesthetic drugs in critically ill patients presents a particular challenge, due to alterations in drug absorbtion and metabolism as well as changes in drug distrubution, which arise from fluid shifts and altered protein binding. Furthermore, side effects associated with prolonged infusions of anaesthetic drugs can lead to multi-organ dysfunction and a need for critical care support. Electroencelography can identify patterns of burst suppression, which may be a target to guide weaning of intravenous therapy. Continuous elctroencephalography has the potential to directly impact clinical care, but despite its utility, major barriers exist which have limited its widespread use in clinical practice. A flow chart outlining the timing and dosage of anaesthetic agents used at our institution is provided.

Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research.

BACKGROUND: Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS). METHODS: Retrospective analysis. Data were identified by using MEDLINE® database and the terms "video laryngoscopy" and "video laryngoscope" limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding. RESULTS: In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items "time to intubation" (65.86%), "laryngeal view grade" (44.89%), "successful intubation rate" (36.56%), "number of intubation attempts" (23.39%), "complications" (21.24%), and "successful first-pass intubation rate" (19.09%) were reported most frequently. A total of 19 specific parameters is recommended. CONCLUSIONS: In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., "time to intubation" (inserting the laryngoscope to first ventilation), "laryngeal view grade" (C&L and POGO), "successful intubation rate", etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.

Trends in endpoint selection and result interpretation in advanced non-small cell lung cancer clinical trials published between 2000 and 2012: A retrospective cohort study.

BACKGROUND: The objective of this review was to investigate trends in clinical trial design, specifically, the primary outcomes used, interpretation of results, and the magnitude of the benefits described in phase III controlled clinical trials in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seventy-six trials published between 2000 and 2012 were selected from a total of 122 identified in a structured search. RESULTS: Overall survival (OS) was evaluated as the primary study endpoint in 50 (65.8%) trials, followed by progression-free survival (PFS) in 15 (19.7%), and other variables, such as toxicity, quality of life (QoL), and response rate in 11 (14.5%). Ten (66.7%) out of 15 clinical trials using PFS as the primary endpoint were published between 2010 and 2012. Median overall survival (mOS) was 9.90 months (interquartile range: 3.5) with an increase of 0.384 months per year of publication (P < 0.001). A statistically significant improvement in mOS was obtained in only 13 (18.8%) trials. A total of 41 (53.9%) studies concluded that the result was positive. Of these, only 16 (39.1%) showed a statistically significant benefit in OS. QoL was assessed in 46 trials (60.5%) and of these, 10 (21.7%) reported significant improvements. CONCLUSIONS: These findings raise important questions about how clinical benefits are measured in clinical trials in advanced NSCLC. Appropriate clinically relevant outcome variables should be established and validated, and post-marketing studies should be requested by regulatory authorities to ensure meaningful clinical benefits in OS and QoL.

Longitudinal multimodal imaging and clinical endpoints for frontotemporal dementia clinical trials.

Frontotemporal dementia refers to a group of progressive neurodegenerative syndromes usually caused by the accumulation of pathological tau or TDP-43 proteins. The effects of these proteins in the brain are complex, and each can present with several different clinical syndromes. Clinical efficacy trials of drugs targeting these proteins must use endpoints that are meaningful to all participants despite the variability in symptoms across patients. There are many candidate clinical measures, including neuropsychological scores and functional measures. Brain imaging is another potentially attractive outcome that can be precisely quantified and provides evidence of disease modification. Most imaging studies in frontotemporal dementia have been cross-sectional, and few have compared longitudinal changes in cortical volume with changes in other measures such as perfusion and white matter integrity. The current study characterized longitudinal changes in 161 patients with three frontotemporal dementia syndromes: behavioural variant frontotemporal dementia (n = 77) and the semantic (n = 45) and non-fluent (n = 39) variants of primary progressive aphasia. Visits included comprehensive neuropsychological and functional assessment, structural MRI (3 T), diffusion tensor imaging, and arterial spin labelled perfusion imaging. The goal was to identify measures that are appropriate as clinical trial outcomes for each group, as well as those that might be appropriate for trials that would include more than one of these groups. Linear mixed effects models were used to estimate changes in each measure, and to examine the correlation between imaging and clinical changes. Sample sizes were estimated based on the observed effects for theoretical clinical trials using bootstrapping techniques to provide 95% confidence intervals for these estimates. Declines in functional and neuropsychological measures, as well as frontal and temporal cortical volumes and white matter microstructure were detected in all groups. Imaging changes were statistically significantly correlated with, and explained a substantial portion of variance in, the change in most clinical measures. Perfusion and diffusion tensor imaging accounted for variation in clinical decline beyond volume alone. Sample size estimates for atrophy and diffusion imaging were comparable to clinical measures. Corpus callosal fractional anisotropy led to the lowest sample size estimates for all three syndromes. These findings provide further guidance on selection of trial endpoints for studies in frontotemporal dementia and support the use of neuroimaging, particularly structural and diffusion weighted imaging, as biomarkers. Diffusion and perfusion imaging appear to offer additional utility for explaining clinical change beyond the variance explained by volume alone, arguing for considering multimodal imaging in treatment trials.

Rationale, design, and endpoints of the 'DEvice-Detected CArdiac Tachyarrhythmic Events and Sleep-disordered Breathing (DEDiCATES)' study: Prospective multicenter observational study of device-detected tachyarrhythmia and sleep-disordered breathing.

BACKGROUND: Few studies have investigated the prognostic value of cardiac implantable electronic device (CIED)-detection of sleep-disordered breathing (SDB) for risk stratification of cardiovascular events. In the Device-Detected CArdiac Tachyarrhythmic events and Sleep-disordered breathing (DEDiCATES) study, we aim to determine whether device-detected SDB events are associated with increased risk of cardiac arrhythmias or other cardiovascular outcomes. METHODS AND DESIGN: Six-hundred patients (300 patients with low-voltage pacing devices and 300 with high-voltage defibrillator devices) who have dual chamber CIEDs with AP Scan™ function (Boston Scientific Inc., Marlborough, MA, USA) are planned to be enrolled in this study. AP Scan reports the average number of sleep disturbance events per hour per night in the form of a Respiratory Disturbance Index (RDI). The daily RDI values are to be used for quantitative measurement of the severity and burden of SDB. CIED-detected atrial high rate episodes (AHREs) and clinical atrial tachyarrhythmia will be assessed as the primary outcomes over a follow-up period of 2 years. Correlations between CIED-detected SDB and AHRE burdens will be analyzed. The secondary outcomes are CIED-detected or clinical ventricular arrhythmic events, stroke, heart failure hospitalization, mortality, and quality of life. CONCLUSION: This study will determine the prognostic value of automated diagnostic function of CIED for SDB, which will help to improve the cardiovascular prognoses of CIED patients by enabling convenient and accurate assessments of SDB events.

Ventricular tachycardia ablation in structural heart disease: Impact of ablation strategy and non-inducibility as an end-point on long term outcome.

BACKGROUND: To investigate the long term outcomes after catheter ablation (CA) of ventricular tachycardia (VT) in the context of structural heart disease in a multicenter cohort. The impact of different ablation strategies (substrate ablation versus activation guided versus combined) and non-inducibility as an end-point was evaluated. METHODS: Data was pooled from prospective registries at 5 centres over a 5 year period. Success was defined as survival free from recurrent ventricular arrhythmias (VA). Multivariate analysis of factors predicting survival free from VA was analysed by Cox regression. RESULTS: Five hundred sixty-six patients underwent CA for VT. Patients were 64 ±â€¯15 years. Left ventricular ejection fraction was 35 ±â€¯15% and 66% had ischaemic heart disease. At 2.3 (IQR 1.0-4.2) years, success was achieved in 44% after a single procedure, rising to 60% after repeat procedures. Mortality at final follow up was 22%. Multivariate analysis showed that higher left ventricular ejection fraction, younger age, ischaemic heart disease, and non-inducibility of VA predicted long term survival free from VA (all p < 0.05). There was no impact of the approach to ablation. CONCLUSION: CA eliminates VT in a large proportion of patients long term. Ablation strategy did not impact outcome and hence substrate ablation is a reasonable initial strategy. Non-inducibility of VA predicted survival free from VA and may be worth pursuing as a procedural end-point.

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials.

A systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure.

BACKGROUND: In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. METHODS: Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. RESULTS: The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. CONCLUSIONS: There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined.

Pharmacological vs. classical approaches in the design of first in man clinical drug trials.

AIMS: The aims of the present study were to investigate the role of pharmacology in the design of first-in-man (FIM) trials in the Netherlands, and to evaluate the change in design approaches between 2007 and 2015. METHODS: All FIM drug trials approved by all Dutch Institutional Review Boards (IRBs) in 2007 and in 2015 were selected. The original trial protocols, investigator's brochures and investigational medicinal product dossiers were the data sources. The following four design elements were assessed on the justification of the chosen approaches: preclinical information, dose calculation, endpoints, and dose escalation. RESULTS: In 2007, the Dutch IRBs approved 21 FIM trials, and in 2015 they approved 34 FIM trials (55 in total). Seven out of 21 (33%) of the FIM trials from 2007, and 14 out of the 34 (41%) FIM trials from 2015 discussed only the no-observed-adverse-effect level or no-observed-effect level as preclinical information. Furthermore, five of the 21 (24%) 2007 FIM trials and 12 of the 34 (35%) 2015 FIM trials used unexplained allometric scaling. Pharmacodynamic (PD) parameters were measured in 15 of the 21 (71%) 2007 FIM trials and in 31 of the 34 (91%) of the 2015 FIM trials, and allometric scaling was only guided by safety/tolerability in 11 of the 20 (55%) dose escalation trials in 2007 and in nine of the 33 (27%) dose escalation trials in 2015. CONCLUSIONS: Trial protocols and investigator's brochures commonly lack pharmacokinetic/PD approaches. Investigators, sponsors and IRBs should require an upfront consideration of pharmacology in these aspects for all FIM trials.

Temporal Trends in Use of Composite End Points in Major Cardiovascular Randomized Clinical Trials in Prominent Medical Journals.

BACKGROUND: Cardiovascular mortality has decreased over the past 5 decades, making it increasingly difficult to demonstrate significant benefits of new therapies in randomized clinical trials. We sought to determine whether the use of composite end points in major cardiovascular trials has changed over time and examine temporal trends in the clinical importance of individual components of these composite end points. METHODS AND RESULTS: Using a validated search strategy, we searched MEDLINE for randomized trials of therapies for primary or secondary cardiovascular prevention published in New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association between 1986 and 2015. We abstracted and categorized study population demographics, type of intervention, and primary and secondary outcomes. Composite end point components were ranked according to importance (minor, moderate, major, critical, and death) and temporal trends analyzed. In total, 604 of 2607 trials retrieved met inclusion criteria. Use of composite end points increased significantly over time from 18.8% between 1986 and 1990 to 83.0% between 2011 and 2015 (P<0.001). The number of components in the primary end point also increased significantly (median 1 in 1986-1990, median 3 in 2011-2015; P<0.001). Contemporary trials were more likely to include end points of lesser importance to patients (minor 3.1% and moderate 6.3% in 1986-1990, minor 4.5% and moderate 44.6% in 2011-2015; P<0.001). Use of death as the sole primary end point declined significantly over time (53.1% in 1986-1990, 17.9% in 2011-2015; P<0.001). CONCLUSIONS: Contemporary cardiovascular randomized clinical trials are more likely to use primary composite end points that contain a larger number of components. Furthermore, these composite end points have increasingly incorporated components of lesser clinical importance. Clinicians and policymakers interpreting results of randomized trials should recognize that the significance of individual components in a composite end point is often heterogeneous.

Stiffness After Pan-Lumbar Arthrodesis for Adult Spinal Deformity Does Not Significantly Impact Patient Functional Status or Satisfaction Irrespective of Proximal Endpoint.

STUDY DESIGN: Prospective, multicenter. OBJECTIVE: To determine if stiffness significantly affects function or satisfaction after pan-lumbar arthrodesis. SUMMARY OF BACKGROUND DATA: The Lumbar Stiffness Disability Index (LSDI) is a validated measure of the effect of lumbar stiffness on functional activities. Data suggests that patients undergoing fusion of the entire lumbar spine are at greatest risk of functional limitations from stiffness. METHODS: The LSDI, Short Form 36, Scoliosis Research Society-22, and Oswestry Disability Index were administered preoperatively and at 2-year minimum follow-up to 103 spinal deformity patients from 11 centers. Patients were separated according to the proximal arthrodesis level; upper thoracic (T2-5) to pelvis (UT-Pelvis) or thoraco-lumbar (T10-T12) to pelvis (TL-Pelvis). Outcome scores were compared using Student t test or Tukey-Kramer Honest Significant Difference Analysis of Variance. Regression analysis of final LSDI scores versus Scoliosis Research Society-22 Satisfaction scores was performed. RESULTS: Mean ages, baseline values, and final scores of all outcome parameters were statistically equivalent in the two groups. Final LSDI scores did not change significantly from baseline in the UT-Pelvis (P = 0.478) or TL-Pelvis (P = 0.301) groups. In contrast, highly significant improvements (P ≤ 0.0001) from baseline were seen in both groups for other health-related QoL measures. The 2-year Satisfaction scores were statistically equivalent in the two groups, and the correlation between final LSDI and Satisfaction scores in the entire cohort was not significant (R = 0.013, P = 0.146). CONCLUSION: Patients undergoing pan-lumbar arthrodesis for adult spinal deformity did not experience substantial increases in disability due to stiffness of the low back, although they did report significant improvements in other health-related QoL measures. Further, LSDI scores did not correlate with patient satisfaction. There were no significant differences in perceived stiffness effects whether arthrodesis stopped in the thoracolumbar or upper thoracic regions. We hope these results will be useful to spine surgeons and patients during preoperative planning and discussions. LEVEL OF EVIDENCE: 2.

Treatment Targets in Inflammatory Bowel Disease: Current Status in Daily Practice.

BACKGROUND AND AIMS: Recently, treatment goals in inflammatory bowel disease (IBD) in clinical trials have shifted from mainly symptom-based to more mucosa-driven. Real world data on treatment priorities are lacking. We aimed to investigate the current practice and most commonly used definitions of IBD treatment targets among Dutch gastroenterologists. METHODS: Dutch gastroenterologists were asked to participate in a computer-based nation-wide survey. We asked questions on demographics, opinion and current practice regarding IBD treatment targets. RESULTS: Twenty-four percent (134/556) of the respondents completed the survey. For both Crohn's disease (CD) (47.3%, 61/129) and ulcerative colitis (UC)(45%, 58/129) the main treatment goal was to achieve and maintain deep remission, defined as clinical, biochemical and endoscopic remission. Seventy-six percent of the participants use mucosal healing (MH) as a potential treatment target for IBD, whereas 22.6% use histological remission. There is no single definition for MH in IBD. The majority use Mayo score ≤ 1 in UC (52%) and 'macroscopic normal mucosa' in CD (66%). CONCLUSION: More stringent and mucosa-driven treatment targets as 'deep remission' and 'mucosal healing' have found traction in clinical practice. The most commonly used definition for MH in routine practice is endoscopic MAYO score

Trends in endpoint selection in clinical trials of advanced breast cancer.

PURPOSE: The selection of appropriate endpoints is crucial for the evaluation of clinical benefits and approval of novel anticancer agents. To our knowledge, this is the first study to evaluate endpoint selection and the shift in trends in phase II and phase III trials of advanced breast cancer treatment. METHODS: All phase II and phase III trials of advanced breast cancer registered in the ClinicalTrials.gov registry between October 2000 and September 2012 were included in our study. Two study periods were considered for comparison: October 2000 to September 2007 (cohort A) and October 2007 to September 2012 (cohort B). Information on primary and secondary outcome measures, as well as trial characteristics, was extracted by two independent reviewers. RESULTS: Of the 398 phase II and 120 phase III trials, the most frequently intended primary endpoint was progression-free survival (phase II: 28.1 %; phase III: 50.0 %). For phase II trials, a shifting trend in primary outcome was observed from cohort A to cohort B: the use of objective response rate, the most frequently intended primary outcome, significantly declined (cohort A: 60.6 %; cohort B: 39.0 %; P < 0.001), while the use of progression-free survival significantly increased (cohort A: 35.9 %; cohort B: 66.1 %; P < 0.001). CONCLUSIONS: Progression-free survival is the most frequently intended primary outcome measure in phase II and phase III trials of advanced breast cancer treatment, with a shifting trend observed from objective response rate to progression-free survival in phase II trials.