Patient-centric Comparability Assessment of Biopharmaceuticals.

The comparability assessment of a biological product after implementing a manufacturing process change should involve a risk-based approach. Process changes may occur at any stage of the product lifecycle: early development, clinical manufacture for pivotal trials, or post-approval. The risk of the change to impact product quality varies.

Helping reviewers assess statistical analysis: A case study from analytic methods.

Analytic methods development, like many other disciplines, relies on experimentation and data analysis. Determining the contribution of a paper or report on a study incorporating data analysis is typically left to the reviewer's experience and good sense, without reliance on structured guidelines. This is amplified by the growing role of machine learning driven analysis, where results are based on computer intensive algorithm applications.

To tolerate or to agree: A tutorial on tolerance intervals in method comparison studies with BivRegBLS R Package.

The well-known agreement interval by Bland and Altman is extensively applied in method comparison studies. Two clinical measurement methods are considered interchangeable if their differences are not clinically significant. The agreement interval is commonly applied to assess the spread of the differences.

Confidence, prediction, and tolerance in linear mixed models.

The literature about Prediction Interval (PI) and Tolerance Interval (TI) in linear mixed models is usually developed for specific designs, which is a main limitation to their use. This paper proposes to reformulate the two-sided PI to be generalizable under a wide variety of designs (one random factor, nested and crossed designs for multiple random factors, and balanced or unbalanced designs). This new methodology is based on the Hessian matrix, namely, the inverse of (observed) Fisher Information matrix, and is built with a cell mean model.

Pedicle screw insertion accuracy in terms of breach and reposition using a new intraoperative cone beam computed tomography imaging technique and evaluation of the factors associated with these parameters of accuracy: a series of 695 screws.

Purpose: The goals of this study were to assess the accuracy of pedicle screw insertion using an intraoperative cone beam computed tomography (CBCT) system, and to analyze the factors potentially influencing this accuracy.

Methods: Six hundred and ninety-five pedicle screws were inserted in 118 patients between October 2013 and March 2016. Screw insertion was performed using 2D-fluoroscopy or CBCT-based navigation.

Accuracy of a new intraoperative cone beam CT imaging technique (Artis zeego II) compared to postoperative CT scan for assessment of pedicle screws placement and breaches detection.

Purpose: The goal of this study was to compare the accuracy of a novel intraoperative cone beam computed tomography (CBCT) imaging technique with that of conventional computed tomography (CT) scans for assessment of pedicle screw placement and breach detection.

Methods: Three hundred and forty-eight pedicle screws were inserted in 58 patients between October 2013 and March 2016. All patients had an intraoperative CBCT scan and a conventional CT scan to verify the placement of the screws.

Erratum to: Methods for evaluating medical tests and biomarkers.

[This corrects the article DOI: 10.1186/s41512-016-0001-y.].

A Randomized, Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and Hemodiafiltration.

Background: The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD.

Delta method and bootstrap in linear mixed models to estimate a proportion when no event is observed: application to intralesional resection in bone tumor surgery.

Resecting bone tumors requires good cutting accuracy to reduce the occurrence of local recurrence. This issue is considerably reduced with a navigated technology. The estimation of extreme proportions is challenging especially with small or moderate sample sizes.

How to regress and predict in a Bland-Altman plot? Review and contribution based on tolerance intervals and correlated-errors-in-variables models.

Two main methodologies for assessing equivalence in method-comparison studies are presented separately in the literature. The first one is the well-known and widely applied Bland-Altman approach with its agreement intervals, where two methods are considered interchangeable if their differences are not clinically significant. The second approach is based on errors-in-variables regression in a classical (X,Y) plot and focuses on confidence intervals, whereby two methods are considered equivalent when providing similar measures notwithstanding the random measurement errors.

Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial.

Aims: To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status.

Methods And Results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.

Normal limits of the electrocardiogram in Indians.

Aims: The objective of the study was to develop normal limits of the ECG in an apparently healthy population of South Asians living in India.

Methods: Three centres contributed to recording 12 lead ECGs on identical digital electrocardiographs. Apparently healthy volunteers were recruited and ECGs were first transferred to a local database and then to Glasgow where all ECGs were analysed by the same University of Glasgow ECG Interpretation Program.

Local complications of massive bone allografts: an appraisal of their prevalence in 128 patients.

Bone allografts were used in our department since twenty-five years to reconstruct segmental bone loss and our data were retrospectively reviewed to assess the complications related to the use of a bone allograft. A consecutive series of 128 patients who received a bone allograft was analyzed. The minimal follow-up was 18 months.

Improved accuracy with 3D planning and patient-specific instruments during simulated pelvic bone tumor surgery.

In orthopaedic surgery, resection of pelvic bone tumors can be inaccurate due to complex geometry, limited visibility and restricted working space of the pelvis. The present study investigated accuracy of patient-specific instrumentation (PSI) for bone-cutting during simulated tumor surgery within the pelvis. A synthetic pelvic bone model was imaged using a CT-scanner.

Computer-assisted planning and navigation improves cutting accuracy during simulated bone tumor surgery of the pelvis.

Background: Resection of bone tumors within the pelvis requires good cutting accuracy to achieve satisfactory safe margins. Manually controlled bone cutting can result in serious errors, especially due to the complex three-dimensional geometry, limited visibility, and restricted working space of the pelvic bone. This experimental study investigated cutting accuracy during navigated and non-navigated simulated bone tumor cutting in the pelvis.

Accuracy in planar cutting of bones: an ISO-based evaluation.

Background: Computer- and robot-assisted technologies are capable of improving the accuracy of planar cutting in orthopaedic surgery. This study is a first step toward formulating and validating a new evaluation methodology for planar bone cutting, based on the standards from the International Organization for Standardization.

Methods: Our experimental test bed consisted of a purely geometrical model of the cutting process around a simulated bone.

Surgical inaccuracy of tumor resection and reconstruction within the pelvis: an experimental study.

Background And Purpose: Osseous pelvic tumors can be resected and reconstructed using massive bone allografts. Geometric accuracy of the conventional surgical procedure has not yet been documented. The aim of this experimental study was mainly to assess accuracy of tumoral resection with a 10-mm surgical margin, and also to evaluate the geometry of the host-graft reconstruction.