scholarly journals An adaptive two-arm clinical trial using early endpoints to inform decision making: design for a study of sub-acromial spacers for repair of rotator cuff tendon tears

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Nick Parsons ◽  
Nigel Stallard ◽  
Helen Parsons ◽  
Philip Wells ◽  
Martin Underwood ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Rotator Cuff ◽  
Surgical Procedures ◽  
Adaptive Designs ◽  
Operating Characteristics ◽  
Worked Example ◽  
Patient Reported ◽  
Design Characteristics ◽  
Inform Decision Making

Abstract Background There is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked example, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures. Methods Test statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described. Results Simulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked example, with code in R, provides a practical demonstration of how the design might work in a real study. Conclusions In summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study. Trial registration ISRCTN Registry, ISRCTN17825590. Registered on 5 March 2018.

Machine learning algorithms to predict financial toxicity associated with breast cancer treatment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2047-2047 ◽  
Author(s):  
Chris Sidey-Gibbons ◽  
Malke Asaad ◽  
André Pfob ◽  
Stefanos Boukovalas ◽  
Yu-Li Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Decision Making ◽  
Cancer Treatment ◽  
Financial Burden ◽  
Breast Cancer Treatment ◽  
Support Vector ◽  
Financial Toxicity ◽  
Operating Characteristics ◽  
Patient Reported

2047 Background: Financial burden caused by cancer treatment is associated with material loss, distress, and poorer outcomes. Financial resources exist to support patients but objective identification of individuals in need is difficult. Accurate predictions of an individual’s risk of financial toxicity prior to initiation of breast cancer treatment may facilitate informed clinical decision making, reduce financial burden, and improve patient outcomes. Methods: We retrospectively surveyed 611 patients who had undergone breast cancer therapy at MD Anderson Cancer Center to assess the financial impact of their care. All patients were over 18 and received either a lumpectomy or a mastectomy. We collected data using the FACT-COST patient-reported outcome measures alongside other financial indicators including income and insurance status. We extracted clinical and perioperative data from the electronic health record. Missing data were imputed using multiple imputation. We used this data to train and validate a neural network, LASSO-regularized linear model, and support vector machines. Data were randomly partitioned into training and validation samples (3:1 ratio). Analyses were informed by international PROBAST recommendations for developing multivariate predictors. We combined algorithms into a voting ensemble and assessed predictive performance using area under the receiver operating characteristics curve (AUROC), accuracy, sensitivity, and specificity. Results: In our validation sample, 48 of 203 (23.6%) women reported FACT-COST scores commensurate with significant financial burden. The algorithm predicted significant financial burden relating to cancer treatment with high accuracy (Accuracy = .83, AUROC = .82, sensitivity = .81, specificity = .82). Key clinical predictors of financial burden from linear models were neo-adjuvant therapy (βregularized 0.12) and autologous, rather than implant-based, reconstruction (βregularized 0.10). Conclusions: Machine learning models were able to accurately predict the occurrence of financial toxicity related to breast cancer treatment. These predictions may be used to inform decision making and care planning to avoid financial distress during cancer treatment or to enable targeted financial support for individuals. Further research is warranted to further improve this tool and assess applicability for other types of cancer.

scholarly journals Bayesian Utility-Based Designs for Subgroup-Specific Treatment Comparison and Early-Phase Dose Optimization in Oncology Clinical Trials

2019 ◽  
pp. 1-7
Author(s):  
Peter F. Thall
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Patient Outcomes ◽  
Early Phase ◽  
Operating Characteristics ◽  
Treatment Comparison ◽  
Trade Offs ◽  
Patient Heterogeneity ◽  
Clinical Trial Designs

PURPOSE Despite the fact that almost any sample of patients with a particular disease is heterogeneous, most clinical trial designs ignore the possibility that treatment or dose effects may differ between prognostic or biologically defined subgroups. This article reviews two clinical trial designs that make subgroup-specific decisions and compares each to a simpler design that ignores patient heterogeneity. The purpose is to illustrate the benefits of accounting prospectively for treatment-subgroup interactions and how utilities may be used to quantify risk-benefit trade-offs. METHODS Two Bayesian clinical trial designs that perform subgroup-specific decision making and inference based on elicited utilities of patient outcomes are reviewed. The first is a randomized comparative trial of nutritional prehabilitation for patients undergoing esophageal resection that has two prognostic subgroups and is based on postoperative morbidity score. The second is a sequentially adaptive trial of natural killer cells for treating hematologic malignancies that is based on five time-to-event outcomes and that performs safety monitoring and optimizes cell dose within six disease subgroups. Computer simulations under a range of different scenarios are presented for each design to establish its operating characteristics and compare it to a more conventional design that ignores patient heterogeneity. RESULTS Each design has attractive operating characteristics, is greatly superior to a simplified design that ignores patient subgroups, is robust to deviations from its assumed statistical model, and is feasible to use for conducting trials. CONCLUSION Bayesian designs that make subgroup-specific decisions in randomized comparative trials or sequentially adaptive early-phase dose-finding trials are superior to designs that ignore patient heterogeneity. Using elicited utilities of complex patient outcomes to quantify risk-benefit trade-offs provides a practical and ethical basis for decision making and treatment evaluation in clinical trials.

PP054 The All Wales Patient Reported Outcome Measures (PROMs), Patient Reported Experience Measures (PREMs) and Effectiveness Program

2017 ◽  
Vol 33 (S1) ◽  
pp. 97-98
Author(s):  
Kathleen Withers ◽  
Robert Palmer ◽  
Grace Carolan-Rees
Keyword(s):  
Decision Making ◽  
Outcome Measures ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Smoking History ◽  
Health Board ◽  
National Guidelines ◽  
Patient Reported ◽  
Oxford Hip Score ◽  
Inform Decision Making

INTRODUCTION:Prudent health care aims to do the minimum needed to achieve the greatest patient benefit. This aim relies on the availability of evidence on the safety and efficacy of interventions to support decision making. The principles of prudent healthcare support co-production, whereby service users contribute to service provision. Collection of patient reported data is becoming more widespread, however use of this data to inform decision making is limited.METHODS:A national patient reported outcome measures (PROMs) program has been formed supported by the Welsh Government, Welsh Health Boards and the NHS Wales Informatics Service. An electronic platform has been developed to facilitate collection of PROMs and patient reported experience measures (PREMs) from patients treated in secondary care. We collected baseline PROMs where possible and invited patients to submit PROMs and PREMs post-treatment. Data collected included EuroQuol five dimensions questionnaire (EQ5D), co-morbidities, body mass index (BMI), smoking history and alcohol intake. Disease specific tools were used where available and responses linked to clinical data. Individual level data will be available during clinic consultations, and collated data analyzed on national and health board levels to assess clinical effectiveness. The platform is currently being piloted in several sites across Wales.RESULTS:Initial baseline pilot data from hip replacement patients found that over 55 percent of responders were classed as overweight or obese, with over 80 percent carrying out less than the national guidelines for exercise.The baseline scores for hip patients were; EQ-5D Index (Mean .29, median .29, range (-.59 -1)), EuroQol-visual analogue scales (EQ-VAS) (Mean 57.8, median 60, range (0:100)), and Oxford Hip Score (Mean 14.9, median 14, range (0:48)).When compared to baseline scores collected by NHS England in 2015/16 (1), the average EQ5D Index and Oxford Hip Score collected in Wales was lower than that in England (p< .05).CONCLUSIONS:The program will provide a large dataset from patients across all of Wales with data on numerous chronic and acute conditions. The data collected will facilitate service improvements and will inform decision making as part of the prudent healthcare agenda.

Medical support to Operation CORPORATE

2017 ◽  
Vol 103 (2) ◽  
pp. 83.3-88
Author(s):  
J G Penn-Barwell ◽  
R Jolly ◽  
R Rickard
Keyword(s):  
Decision Making ◽  
Surgical Procedures ◽  
Wound Management ◽  
Falkland Islands ◽  
Medical Support ◽  
Previous Generation ◽  
Management Procedures ◽  
The Future ◽  
The Uk ◽  
Inform Decision Making

AbstractThis article describes the medical support to Operation CORPORATE, and is derived from a range of sources, including surgical operative logbooks, journals and contemporaneous official reports.Eight hundred and fifty-five surgical procedures were performed by deployed medical units between 14 May and 13 July 1982 in support of Op CORPORATE. The rate peaked on the busiest day, 12 June 1982, when 86 operations were performed. The vast majority of operations were wound management procedures, although 20 laparotomies, four thoracotomies and six craniotomies were also performed. The four forward Role 2 (R2) surgical facilities at Ajax Bay, Teal Inlet, Fitzroy and on board SS CANBERRA collectively performed 354 operations.Argentine and British casualties were evacuated from the area of operations on board three Argentine vessels and three British HECLA-class survey ships. Between them, HMSs HECLA, HYDRA and HERALD made a total of nine 1000-NM journeys between the Falkland Islands and Montevideo, Uruguay, caring for a total of 601 patients. From Montevideo, British casualties were transferred by RAF VC-10 back to the UK.Reflection on how a previous generation supported this operation may inform decision-making when similar challenges are faced in the future.

scholarly journals Patient reported outcome after stemmed versus stemless total shoulder arthroplasty for glenohumeral osteoarthritis: a patient-blinded randomized clinical trial

2019 ◽  
Author(s):  
Zaid Issa ◽  
Jeppe Vejlgaard Rasmussen ◽  
John Kloth Petersen ◽  
Kim Schantz ◽  
Stig Brorson
Keyword(s):  
Clinical Trial ◽  
Rotator Cuff ◽  
Randomized Clinical Trial ◽  
Shoulder Arthroplasty ◽  
Total Shoulder Arthroplasty ◽  
Revision Arthroplasty ◽  
Patient Reported Outcome ◽  
Bone Stock ◽  
Patient Reported ◽  
Glenohumeral Osteoarthritis

Abstract Background Stemless shoulder arthroplasty systems with uncemented metaphyseal fixation have been used in Europe for glenohumeral osteoarthritis since 2004 [1]. The stemless design has several theoretical advantages compared with the stemmed shoulder arthroplasty systems: restoring patients’ anatomy, preserving humeral bone stock, and few complications in component removal if the need for a revision arthroplasty arises. The purpose of the study is to compare the short-term, patient-reported outcome of stemless and stemmed total shoulder arthroplasty. Materials and methods A randomized clinical trial will be conducted. Eighty patients with clinical and radiological signs of primary or posttraumatic glenohumeral osteoarthritis, computerized tomography (CT) scan-verified adequate glenoid bone stock, and no total rupture of rotator cuff tendons verified by a magnetic resonance imaging (MRI) scan will randomly be allocated to a stemless or stemmed total shoulder arthroplasty (TSA). The primary outcome will be the Western Ontario Osteoarthritis Shoulder (WOOS) score at 12 months. Secondary outcomes are the WOOS score at three months and the Oxford Shoulder Score (OSS) and EQ-5D at 3 and 12 months. All complications, including glenoid and humeral component loosening, instability, rotator cuff tear, intraoperative and postoperative periprosthetic fracture, nerve injury, infection, deltoid injury, and symptomatic deep venous thrombosis, will be reported. Discussion Findings will provide patients with better information about the potential benefits and harms of stemless and stemmed total shoulder arthroplasty and will assist shoulder surgeons and patients in decision-making.

Comparison of a Novel Tazarotene 0.045% Lotion to Tazarotene 0.1% Cream: Patient-Reported Outcomes from a Phase 2 Clinical Trial

2019 ◽  
Vol 3 ◽  
pp. S9
Author(s):  
Zoe Draelos ◽  
Fran Cook-Bolden ◽  
Lawrence Green ◽  
Eric Guenin ◽  
Gina Martin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Patient Reported Outcomes ◽  
Phase 2 ◽  
Patient Reported ◽  
Phase 2 Clinical Trial

Abstract not available.

Is the Deductive Falsification Approach a Better Basis for Clinical Trial Appraisal?

2019 ◽  
Vol 14 (3) ◽  
pp. 224-228
Author(s):  
Steffen Mickenautsch
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Empirical Evidence ◽  
Clinical Decision Making ◽  
Inductive Reasoning ◽  
Clinical Decision ◽  
Future Trial ◽  
Grading Systems ◽  
Component Scores ◽  
Current Clinical Trial

Background: Inductive reasoning relies on an infinite regress without sufficient factual basis and verification is at any time vulnerable to single contrary observation. Thus, appraisal based on inductive verification, as applied in current clinical trial appraisal scales, checklists or grading systems, cannot prove or justify trial validity. Discussion: Trial appraisal based on deductive falsification can identify invalid trials and give evidence for the recommendation to exclude these from clinical decision-making. Such appraisal remains agnostic towards corroborated trials that pass all appraisal criteria. The results of corroborated trials cannot be considered more robust than falsified trials since nothing within a particular set of complied trial criteria can give certainty for trial compliance with any other appraisal criterion in future. A corroborated trial may or may not reflect therapeutic truth and may thus be the basis for clinical guidance, pending results of any future trial re-appraisal. Conclusion: Trial grading following appraisal based on deductive falsification should be binary (0 = Invalid or 1 = Unclear) and single component scores should be multiplied. Appraisal criteria for the judgment of trial characteristics require a clear rationale, quantification of such rationale and empirical evidence concerning the effect of trial characteristics on trial results.

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