Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design

Abstract Background The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing. Methods/Design The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT. Discussion This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases Trial Registration ClinicalTrials.gov, NCT0081425

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project: Overview of design and methods

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients: 400 patients under 18 years of age to be recruited over 2.5 years. Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres

Changing Needs for Information and Support in an Online System for Parents of Children With Kidney Disease

Background: Pediatric chronic kidney disease is psychologically, financially, and physically demanding on parents providing care. Parents often feel isolated because of the rarity of the condition, and geographic isolation often compounds this perception in Canada. Many parents seek assistance online for both information and social support. Objective: This study examines an online portal, titled “Ability Online,” which was designed to provide support and information to a diverse group of parents using chat facilities, bulletin boards, and e-mail. Specifically, we sought to identify how the technologies offered in this system related to the support and information seeking needs for parents. Secondary aims of determining possible reasons for attrition over time were explored as well. Design: Mixed methodology sequential exploratory design using the qualitative methodology of descriptive interpretation. Setting: Telephone interviews. Patients: Twenty parents of pediatric patients with chronic kidney disease from four Canadian centers who engaged in an online social support system “Ability Online.” Measurements: Interview transcripts generated from 20 taped phone conversations were reviewed from parents who engaged in the online system, and the themes derived from these transcripts served to generate semistructured interview questions that focused on their use of, and perceived benefit from, this technology for social support. Follow-up telephone interviews were then conducted with a 6-person subset of the original group in an effort to further define the impact of technology on their experience. This same smaller cohort provided data on social supports, caregiver satisfaction, and caregiver stress. Results: Many parents experience a progression through which their needs for knowledge and support change over time. Specifically, parents describe a transition from pure information seeking, to seeking parental interaction, mutual support and collaboration, and ultimately to advocacy. Parents described how technology could be used to address those needs. Limitations: Our cohort was slightly more educated and representative of more urban populations than published data reflecting the population of North American pediatric patients living with kidney disease. Conclusions: Our data suggest themes of technology use influencing the goals of online support seeking. While our findings are preliminary, further study may inform Web designers to identify the changing needs of participants in designing such online support networks, and minimize the reasons that participants fail to adopt, or terminate their online experiences

Introduction of Competence by Design to Canadian Nephrology Postgraduate Training

Purpose of the review: The Royal College of Physicians and Surgeons of Canada, with its Competence by Design initiative, is adopting the principles of competency-based medical education for residency training and continuing professional development. This initiative is being undertaken to meet the new standards of medical education in Canada, which include social accountability to meet performance-based outcomes of training. Nephrology is poised to implement Competence by Design into residency training in July 2018 and initiate a continuous quality improvement cycle to periodically renew and update the training requirements to be socially accountable and relevant in the modern age of medicine. The purpose of this review is to describe the process of entrustable professional activity and required training experience development and how they will affect subspecialty training in Canada. Sources of information: The construct of competency-based medical education was derived from existing literature searches of the medical education literature, including documentation provided by the Royal College of Physicians and Surgeons of Canada. The content for each entrustable professional activity and milestone was derived by consensus from the community expertise of the working group, existing speciality training requirements, and elements of training requirements that the Royal College has been mandated to superimpose on all training requirements to meet societal expectations. Methods: The Royal College Specialty Committee in Nephrology participated in 2 years of preparation for this implementation, which has included the creation of a new educational design for the discipline and the elucidation of entrustable professional activities to describe the scope of nephrology practice and to guide teaching, learning, and assessment in residency, and ultimately maintenance of competence in practice. Key findings: This article introduces the set of entrustable professional activities for adult and pediatric nephrology and describes the national consultation as part of an ongoing quality improvement of this work. Limitations: The implementation of Competence by Design will be tested by whether trainees embrace competency-based education by training to just entrustable professional activities, rather than the holistic model idealized in physician training. This is mitigated by the entrustable professional activity development incorporating multiple layers of competencies beyond a procedural skill. Time commitment for faculty will pose additional challenges in increasing the time for assessment of trainees, but is supported by electronic platforms at the Royal College to assist in data gathering and analysis. Implications: Competence by Design in nephrology is an outcomes-based curriculum and assessment platform that aims to train nephrologists to meet societal expectations in an ever-changing and complicated health care system. The goals are to increase safety and professional accountability to society and improve upon the already high standards of training within Canada

The Canadian childhood nephrotic syndrome (CHILDNEPH) study: report on mid-study feasibility, recruitment and main measures

Background: To assess reasons for continuing practice variation in the management of childhood nephrotic syndrome despite expert reviews and guidelines, we are conducting a longitudinal cohort study in children with glucocorticoid sensitive nephrotic syndrome. Objectives of this mid-study report are to describe patient and physician recruitment characteristics, glucocorticoid prescriptions, use of second line agents, biopsy practices, and adherence to study protocol. Methods: Children with new onset nephrotic syndrome and providers are being recruited from all 12 pediatric nephrology centres across Canada with > 2½ years follow-up. Data collection points of observation are over a minimum 36 months. Details of prescribed glucocorticoids and of all second line agents used during treatment are being collected. All relapses are being recorded with time to urinary remission of proteinuria. Results: To date, 243 patients (57.1% male) from 12 centres were included. Median number of patients per centre was 29 (range 2–45), and median age of cohort was 7.3 (IQR 4.2) at enrollment. Forty-eight physicians were recruited, median 5 (range 2–8) per site. Median number of relapses per patient year of follow-up was 2.1 (IQR 4). Cumulative dose variability of glucocorticoids prescribed per episode of proteinuria and length of treatment was observed between participating centres. Conclusion: The Canadian pediatric nephrology community established a longitudinal childhood nephrotic syndrome cohort study that confirms ongoing practice variability. The study will help to evaluate its impact on patient outcomes, and facilitate clinical trial implementation in nephrotic syndrome.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacult

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: Overview of Design and Methods

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients: 400 patients under 18 years of age to be recruited over 2.5 years. Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: overview of design and methods

Abstract Background Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients 400 patients under 18 years of age to be recruited over 2.5 years. Measurements Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres