scholarly journals Study risk assessment of Japan Clinical Oncology Group (JCOG) clinical trials using the European Organisation for Research and Treatment of Cancer (EORTC) study risk calculator

2019 ◽  
Vol 49 (8) ◽  
pp. 727-733
Author(s):  
Kenichi Miyamoto ◽  
Kenichi Nakamura ◽  
Junki Mizusawa ◽  
Christine de Balincourt ◽  
Haruhiko Fukuda
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Risk Calculator ◽  
Ethical Guidelines ◽  
Group 12 ◽  
Source Data ◽  
Medium Risk ◽  
Source Data Verification

Abstract Background New Japanese ethical guidelines for medical researches and the Clinical Trials Act have come into effect and monitoring is mandated for intervention studies. Methods of monitoring can be modified according to a study risk, but there is no established method in Japan regarding how to assess a study risk. EORTC assesses a study risk using their own study risk calculator and classifies their trials into three categories. For each category, different levels of monitoring are applied. This project is aimed to assess the study risks of JCOG trials using the EORTC calculator. Methods We selected clinical trials open to patient recruitment in JCOG as of Nov 2014. Each trial was scored based on the EORTC study risk calculator and classified into three risk categories; low, medium and high. Results A total of 40 studies were included in the assessment. Twenty-seven studies (67.5%) were classified into low risk group, 12 (30%) in medium risk group, and only 1 (2.5%) in high risk group. Clinical trials evaluating multimodality therapy and/or using unapproved drugs tended to be scored higher and most of them were classified into medium or high risk group. Conclusions JCOG conducts central monitoring and site visit audit with sampling source data verification for every trial, which are almost compatible with the way in EORTC for the medium risk group. Because most of the JCOG studies were classified into low or medium risk group, the intensity of monitoring and audit in JCOG was considered as reasonable even from the EORTC perspective.

scholarly journals P1291 Are we ready for machine learning in HCM risk stratification?

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
D M Adamczak ◽  
M Bednarski ◽  
A Rogala ◽  
M Antoniak ◽  
T Kiebalo ◽  
...  
Keyword(s):  
Machine Learning ◽  
High Risk ◽  
Risk Group ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
High Risk Group ◽  
Machine Learning Algorithms ◽  
Left Ventricular Myocardium ◽  
Risk Calculator ◽  
Icd Implantation

Abstract BACKGROUND Hypertrophic cardiomyopathy (HCM) is a heart disease characterized by hypertrophy of the left ventricular myocardium. The disease is the most common cause of sudden cardiac death (SCD) in young people and competitive athletes due to fatal ventricular arrhythmias, but in most patients, however, HCM has a benign course. Therefore, it is of the utmost importance to properly evaluate patients and identify those who would benefit from a cardioverter-defibrillator (ICD) implantation. The HCM SCD-Risk Calculator is a useful tool for estimating the 5-year risk of SCD. Parameters included in the model at evaluation are: age, maximum left ventricular wall thickness, left atrial dimension, maximum gradient in left ventricular outflow tract, family history of SCD, non-sustained ventricular tachycardia and unexplained syncope. Patients’ risk of SCD is classified as low (<4%), intermediate (4-<6%) or high (≥6%). Those in the high-risk group should have an ICD implantation. It can also be considered in the intermediate-risk group. However, the calculator still needs improvement and machine learning (ML) has the potential to fulfill this task. ML algorithm creates a model for solving a specific problem without explicit programming - instead it relies only on available data - by discovering patterns and relations. METHODS 252 HCM patients (aged 20-88 years, 49,6% were men) treated in our Department from 2005 to 2018, have been enrolled. The follow-up lasted 0-13 years (average: 3.8 years). SCD was defined as sudden cardiac arrest (SCA) or an appropriate ICD intervention. All parameters from HCM SCD-Risk Calculator have been obtained and the risk of SCD has been calculated for all patients during the first echocardiographic evaluation. ML model with variables from HCM SCD-Risk Calculator has been created. Both methods have been compared. RESULTS 20 patients reached an SCD end-point. 1 patient died due to SCA and 19 had an appropriate ICD intervention. Among them, there were respectively 6, 7 and 7 patients in the low, intermediate and high-risk group of SCD. 1 patient, who died, had a low risk. The ML model correctly assessed the SCD event only in 1 patient. According to ML, the risk of SCD ≤2.07% was a negative predictor. CONCLUSIONS The study did not show an advantage of ML over HCM SCD-Risk Calculator. Because of the characteristic of the dataset (approximately the same number of features and observations), the selection of machine learning algorithms was limited. Best results (evaluated using LOOCV) were achieved with a decision tree. We expect that bigger dataset would allow improving model performance because of strong regularization need in the current setup.

Patterns of local extension and nodal involvement from 1300 nasopharyngeal carcinoma patients: An imaging-based predictor of distant metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17516-e17516
Author(s):  
Dan Fan ◽  
Ying Wang ◽  
Yifu Tian ◽  
Nancy Y. Lee ◽  
Liangfang Shen
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Invasion ◽  
Mixed Type ◽  
Validation Cohort ◽  
Risk Group ◽  
Distant Metastases ◽  
Incidence Rates ◽  
High Risk Group ◽  
Medium Risk

e17516 Background: Distant metastasis is a main determinant of prognosis in patients with nasopharyngeal carcinoma(NPC). We explored the patterns of disease spread in NPC patients and identified the pattern correlates with distant metastases. Methods: The imaging documents of 1300 consecutive newly diagnosed nasopharyngeal carcinoma between 2012 and 2016 were reviewed. According to the incidence rates of tumor invasion, the anatomic sites were classified into high-risk group (≥50%), medium-risk group (≥10%~ < 50%) and low-risk group ( < 10%). The location of lymph nodes was determined by 2013 updated guidelines for neck node levels. Additionally, we developed a novel classification based on tumor spreading patterns, as shown in Table. Moreover, we validated the prognostic accuracy of the classification in a validation cohort from a different institution, 241 non-metastatic NPC patients were retrospectively enrolled. Kaplan-Meier method and log-rank test were used to analyze all time-to-event data. Results: The incidence rates of tumor invasion were 0.2% ~91.2%, 95.2% cases across the midline. If anatomic sites in high-risk group or median-risk group were involved, the incidence rates in adjacent medium-risk sites or low-risk group were increased. On the contrary, the incidence rates were decreased when the adjacent high-risk sites or median-risk group were not involved. 85.9% cases had involved lymph nodes. Only 3.9% had skip metastases. The incidence rates of nodal involvement were increased when adjacent upper nodal level was involved. In validation cohort, distant metastases were present in 32/241 NPC patients (13.3%) and 3-year distant metastasis-free survival(DMFS) in local, superior, inferior, and mixed type were 95.0%, 91.3%, 89.0%, and 78.7%, respectively. Cumulative survival curves for former three patterns were relatively similar and were clearly separated from mixed type. DMFS was significantly lower for patients with mixed type pattern than for those with other patterns(P = 0.018). Conclusions: Local disease in NPC patients spreads stepwise from proximal sites to more distal sites. The frequency of metastases in the jugular lymph node chains decreased in the cranio-caudal direction. Based on the patterns of tumor extension, an imaging-based predictor of distant metastases was developed and may be used as a prognostic marker for selecting patients to further systemic treatments. [Table: see text]

High Prevalence of Relapse in Australian Children with Ph-like Acute Lymphoblastic Leukemia Despite Risk Adapted Treatment

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1419-1419 ◽  
Author(s):  
Susan L Heatley ◽  
Teresa Sadras ◽  
Eva Nievergall ◽  
Chung Hoow Kok ◽  
Phuong Dang ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Risk Groups ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Medium Risk

Abstract Introduction: While remission rates for childhood acute lymphoblastic leukemia (ALL) now exceed 80%, relapsed ALL remains the leading cause of non-traumatic death in children. Recently, a high-risk group of B-progenitor ALL patients has been identified. Such cases exhibit a gene expression profile similar to that of BCR-ABL1 positive (Ph+) ALL but are BCR-ABL1 negative, and also experience poor treatment outcomes. This subset, termed Ph-like ALL, is characterised by a range of genetic alterations that activate cytokine receptor and kinase signalling, allowing potential targeting by available tyrosine kinase inhibitors (TKI). The frequency of Ph-like ALL in the Australian community and the prognosis in the setting of the first MRD (minimal residual disease) intervention trial by the Australian and New Zealand Children's Haematology/Oncology Group (ANZCHOG ALL8) is unknown. Method: We retrospectively screened 250 unselected samples that were available from children diagnosed with B-ALL, for Ph-like ALL. The children, aged between 1 and 18 years, were enrolled on the ANZCHOG ALL8 trial and recruited from 2002-2011. The criteria for stratification to the high-risk group, based upon Berlin-Frankfurt-Munster (BFM) protocols, were BCR-ABL1 or MLL t(4;11) translocation; poor prednisolone response at day 8; failure to achieve remission by day 33 or high MRD (>5 x10-4) at day 79. MRD was measured by RQ-PCR for patient-specific immunoglobulin and T-cell receptor rearrangements. All patients received a standard BFM four drug induction chemotherapy regimen including a prednisolone pre-phase and intrathecal methotrexate. High-risk patients received a further three novel intensive blocks of chemotherapy followed by transplant in most cases. Patients were screened for Ph-like ALL using a custom Taqman Low Density Array (TLDA) based upon previous reports. Fusions were then confirmed by RT-PCR for 30 known fusions, Sanger sequencing, mRNA sequencing and/or FISH. Results: Ten percent (25/250) of children in this cohort were identified as having Ph-like ALL, with most fusions converging on kinase activating pathways (Table 1). Three Ph-like ALL patients were considered high-risk, the remaining 22 (88%) were medium risk. Five children with Ph-like ALL, that did not have a fusion identified by RT-PCR, are currently under further investigation. Furthermore, 15 of the 20 (75%) of rearrangements involved CRLF2 with 10 (66%) of these children relapsing. Strikingly, 56% (14/25) of children in the ALL8 cohort who were identified as Ph-like subsequently relapsed compared to 16% (36/225) who were not, with significantly worse event free survival (p<0.0001) (Figure 1). Conclusion: Here we demonstrate a significantly higher frequency of relapse amongst Australian children with Ph-like ALL compared to non Ph-like disease despite a MRD-adjusted intensification regimen. In this cohort, these children should be classified as high-risk due to high treatment failure rates with standard/medium risk regimens. Importantly, rapid identification of these patients may guide future intervention with targeted therapies, such as TKI, matched to the causative genetic lesion in this high-risk group. Figure 1. Fusions identified in Ph-like ALL from ANZCHOG ALL8 cohort. Figure 1. Fusions identified in Ph-like ALL from ANZCHOG ALL8 cohort. Figure 2. Kaplan-Meier estimates of event free survival for patients with Ph-like ALL and non Ph-like ALL (all risk groups). Figure 2. Kaplan-Meier estimates of event free survival for patients with Ph-like ALL and non Ph-like ALL (all risk groups). Disclosures Hughes: ARIAD: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Mullighan:Incyte: Consultancy, Honoraria; Cancer Science Institute: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Speakers Bureau; Loxo Oncology: Research Funding. White:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

scholarly journals Predicting complication risk in spine surgery: a prospective analysis of a novel risk assessment tool

2017 ◽  
Vol 27 (1) ◽  
pp. 81-91 ◽  
Author(s):  
Anand Veeravagu ◽  
Amy Li ◽  
Christian Swinney ◽  
Lu Tian ◽  
Adrienne Moraff ◽  
...  
Keyword(s):  
Risk Assessment ◽  
High Risk ◽  
Risk Stratification ◽  
Spine Surgery ◽  
Assessment Tool ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Acs Nsqip ◽  
Medium Risk

OBJECTIVEThe ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort.METHODSThe spinal Risk Assessment Tool (RAT), a novel instrument for the assessment of risk for patients undergoing spine surgery that was developed based on an administrative claims database, was prospectively applied to 246 patients undergoing 257 spinal procedures over a 3-month period. Prospectively collected data were used to compare the RAT to the Charlson Comorbidity Index (CCI) and the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator. Study end point was occurrence and type of complication after spine surgery.RESULTSThe authors identified 69 patients (73 procedures) who experienced a complication over the prospective study period. Cardiac complications were most common (10.2%). Receiver operating characteristic (ROC) curves were calculated to compare complication outcomes using the different assessment tools. Area under the curve (AUC) analysis showed comparable predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI 0.60–0.74] in RAT, 0.669 [95% CI 0.60–0.74] in NSQIP). The CCI was not accurate in predicting complication occurrence (0.55 [95% CI 0.48–0.62]). The RAT produced mean probabilities of 34.6% for patients who had a complication and 24% for patients who did not (p = 0.0003). The generated predicted values were stratified into low, medium, and high rates. For the RAT, the predicted complication rate was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The ACS NSQIP calculator consistently produced complication predictions that underestimated complication occurrence: 3.4% in the low-risk group (observed 12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high-risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP calculator (p = 0.0018).CONCLUSIONSWhile the RAT and ACS NSQIP calculator were both able to identify patients more likely to experience complications following spine surgery, both have substantial room for improvement. Risk stratification is feasible in spine surgery procedures; currently used measures have low accuracy.

Impact of Stratification of Comorbidities on Nutrition Indices and Survival in Patients on Continuous Ambulatory Peritoneal Dialysis

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 153-157 ◽  
Author(s):  
Narayan Prasad ◽  
Amit Gupta ◽  
Archana Sinha ◽  
Anurag Singh ◽  
Raj Kumar Sharma ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Risk ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Comorbid Illness ◽  
Medium Risk ◽  
Risk Patients

Background Case-mix comorbidities and malnutrition influence outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In the present study, we analyzed the influence of stratified comorbidities on nutrition indices and survival in CAPD patients. Patients and Methods We categorized 373 CAPD patients (197 with and 176 without diabetes) into three risk groups: low—age under 70 years and no comorbid illness; medium—age 70 – 80 years, or any age with 1 comorbid illness, or age under 70 years with diabetes; high—age over 80 years, or any age with 2 comorbid illnesses. We then compared nutrition indices and malnutrition by subjective global assessment (SGA) between the three groups. Survival was compared using Kaplan–Meier survival analysis. Results Mean daily calorie and protein intakes in the low-risk group (21 ± 6.7 Kcal/kg, 0.85 ± 0.28 g/kg) were significantly higher than in the medium- (17.6 ± 5.2 Kcal/kg, 0.79 ± 0.25 g/kg) and high-risk (17.5 ± 6.1 Kcal/kg, 0.78 ± 0.26 g/kg) groups ( p = 0.001 and p = 0.04 respectively). Relative risk (RR) of malnutrition was less in the low-risk group (103/147, 70.06%) than in the medium-risk group [135/162, 83.3%; RR: 2.0; 95% confidence interval (CI): 2.1 to 3.4; p = 0.01] or the high-risk group (54/64, 84.4%; RR: 2.3; 95% CI: 2.1 to 4.9; p = 0.03). Mean survivals of patients in the low-, medium-, and high-risk groups were 51 patient–months (95% CI: 45.6 to 56.4 patient–months), 43.3 patient–months (95% CI: 37.8 to 48.7 patient–months), and 29.7 patient–months (95% CI: 23 to 36.4 patient–months) respectively (log-rank: 35.9 patient–months; p = 0.001). The 1-, 2-, 3-, 4-, and 5-year patient survivals in the low-, medium-, and high-risk groups were 96%, 87%, 79%, 65%, and 56%; 89%, 67%, 54%, 43%, and 34%; and 76%, 48%, 31%, 30%, and 30% respectively. Conclusions Intake of calories and protein was significantly lower in the medium-risk and high-risk groups than in the low-risk group. Survival was significantly better in low-risk patients than in medium- and high-risk patients.

Cognitively Impaired Older Adults: Risk Profiles for Institutionalization

2003 ◽  
Vol 15 (4) ◽  
pp. 351-366 ◽  
Author(s):  
Laurel A. Strain ◽  
Audrey A. Blandford ◽  
Lori A. Mitchell ◽  
Pamela G. Hawranik
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
High Risk ◽  
Risk Group ◽  
Disruptive Behaviors ◽  
High Risk Group ◽  
Low Risk ◽  
Cognitively Impaired ◽  
Risk Profiles ◽  
Medium Risk

Background: This study focused on the identification of risk profiles for institutionalization among older adults diagnosed with cognitive impairment-not dementia or dementia in 1991/92 and subsequent institutionalization in the following 5-year period. Methods: Data were from a sample of 123 individuals aged 65+ and their unpaid caregivers in Manitoba, Canada. Cluster analysis was conducted using baseline characteristics of age, cognition, disruptive behaviors, ADLs/IADLs, use of formal in-home services, and level of caregiver burden. Results: Three distinct groups emerged (high-risk [n = 12], medium risk [n = 40], and low risk [n = 71]). The high-risk group had the poorest cognitive scores, were the most likely to exhibit disruptive behaviors, were the most likely to need assistance with ADLs and IADLs, and had the highest level of burden among their caregivers. Follow-up of the groups validated the risk profiles; 75% of the high-risk group were institutionalized within the next 5 years, compared to 45% of the medium-risk group and 21% of the low-risk group. Discussion: The risk profiles highlight the diversity among individuals with cognitive impairment and the opportunity for differential targeting of services for the distinct needs of each group.

scholarly journals A clinical scoring system for predicting tumor recurrence after percutaneous radiofrequency ablation for 3 cm or less hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong Zhu He ◽  
Kun He ◽  
Rui Qin Huang ◽  
Li Wen Liu ◽  
Shao Wei Ye ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Tumor Recurrence ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Derivation Cohort ◽  
Medium Risk ◽  
Clinical Scoring

AbstractPreoperative prediction of tumor recurrence after radiofrequency ablation (RFA) in patients with early hepatocellular carcinoma (HCC) is helpful for clinical decision-making before treatment. A total of 162 patients with HCC of 3 cm or less who were completely ablated by percutaneous RFA were divided into a derivation cohort (n = 108) and a validation cohort (n = 54). Based on X-Tiles software, Kaplan–Meier curve analysis and COX multivariate analysis to obtain valuable predictive indicators, a clinical scoring system for predicting tumor recurrence was established. In the verall cohort, derivation cohort and validation cohort, we found circulating tumor cells (CTC) > 2/3.2 mL, alpha-fetoprotein (AFP) > 20 ng/mL, and des-γ-carboxyprothrombin (DCP) > 40 mAU/mL, maximum tumor diameter > 20 mm, and the number of multiple tumors (≥ 2) are independent risk factors affecting tumor recurrence. Each independent risk factor was assigned a score of 1 to construct a predictive clinical scoring system, and X-Tiles software was used to divide the clinical score into a low-risk group (0 score–1 score), a medium-risk group (2 scores–3 scores), and a high-risk group (4 scores–5 scores). The cumulative tumor recurrence rates of patients in the low-risk group, middle-risk group, and high-risk group in 1 year, 2 years, and 3 years were 19.4%/27.5%/30.9%, 37.0%/63.2%/79.9% and 68.2%/100%/100%, respectively (Low-risk group vs medium-risk group: P < 0.001; medium-risk group vs high-risk group: P < 0.001). This clinical scoring system can predict the prognosis of patients with HCC of 3 cm or smaller undergoing percutaneous RFA, which has certain application value for making preoperative clinical decisions.

scholarly journals Prognosis Evaluation of Universal Acute Coronary Syndrome: The Interplay between SYNTAX Score and ApoB/ApoA1

2020 ◽  
Author(s):  
Xiaotong Wang ◽  
Zhongyu Wang ◽  
Bing Li ◽  
Ping Yang
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Independent Predictor ◽  
High Risk Group ◽  
Low Risk ◽  
Syntax Score ◽  
Coronary Syndrome ◽  
Medium Risk ◽  
Prognosis Evaluation

Abstract Background：Acute coronary syndrome (ACS) is a group of clinical syndromes associated with substantial morbidity and mortality rate. Syntax and Syntax II score used to be a reference for surgical selection of coronary revascularization and prognosis evaluation in patients with 3-vessel or left main artery disease. In addition, apoB/apoA1 is an important predictor of ACS risk. This study aims to assess the prognosis value of different kinds of SYNTAX score together with apoB/apoA1 in universal ACS patients (Regardless of ACS type, lesion location and vessel numbers). Method：396 patients with ACS undergoing percutaneous coronary intervention（PCI）and coronary stenting from 2013 to 2014 were chosen and recorded the major adverse cardiovascular and cerebrovascular events (MACCE) and quality of life during the next 5 years. According to SYNTAX and SYNTAX II score, the patients were divided into low-risk, medium-risk and high-risk groups, and the clinical features, MACCE incidence and EQ-5D score at each time points were compared. And the predictive factors of MACCE incidence were analyzed. Results：①Compared with SYNTAX low-risk group, MACCE incidence in 1 year significantly increased in medium/high risk group（p=0.011）. Compared with SYNTAX II low-risk group, MACCE incidence in 5 years significantly increased in medium and high-risk group（p=0.032）.② Compared with SYNTAX II low-risk group，cardiovascular mortality in 3 and 5 years significantly elevated in high-risk group（p=0.001，p＜0.001 respectively）. ③ Compared with SYNTAX II low and medium-risk group, EQ-5D score in 5 years significantly decreased in high-risk group（p=0.019, p=0.023 respectively）. ④ ApoB/ApoA1 was more likely to be classified as high risk in SYNTAX/SYNTAX II medium and high-risk group（p=0.023，p=0.044 respectively）. ⑤Logistic regression analysis showed that apoB/apoA1 was an independent predictor of MACCE events in hospital and 5 years（p=0.038，p=0.016 respectively），SYNTAX score was an independent predictor of MACCE events in 1 year（medium-risk group：p=0.02；high-risk group：p=0.015）SYNTAX II score was an independent predictor of MACCE events in 5 yeasrs(p=0.003). Conclusions：①SYNTAX score has a high predictive value for short-term prognosis while SYNTAX II score is more predictive of long-term prognosis. ② SYNTAX II score is superior to SYNTAX score in predicting cardiovascular death. ③ The combination of apoB/apoA1 high-risk and SYNTAX II medium and high-risk group is the focus of clinical treatment and long-term follow-up observation.

scholarly journals Clinical Design for Phase II/III Clinical Trials for Testing Therapeutic Interventions in COVID-19 Patients

2020 ◽  
Author(s):  
Shesh Rai ◽  
Chen Qian ◽  
Jianmin Pan ◽  
Anand Seth ◽  
Deo Kumar Srivast ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Sample Size ◽  
Risk Group ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Group Sequential Design ◽  
Group Sequential ◽  
Interim Analyses ◽  
Toxicity Monitoring

Abstract Background Researchers around the world are urgently conducting clinical trials to develop new treatments for reducing mortality and morbidity related to COVID-19. However, due to unknown features of the disease and complexity of the patient population, traditional trial designs may not be optimal in such patients. We propose two independent clinical trials designs based on careful grouping of the expected characteristics of patient population. This could serve as a useful guide for researchers designing COVID-19 related Phase II/III trials. Methods Using the commonly utilized World Health Organization ordinal scale on patient status, we classify patients into three risk groups. In this approach, patients in Stages 3, 4 and 5 are categorized as the intermediate-risk group while patients in Stages 6 and 7 are categorized as the high-risk group. To ensure that an intervention, if deemed efficacious, is promptly made available to vulnerable patients, we propose a group sequential design with two interim analyses along with a final analysis and a toxicity monitoring rule for the intermediate-risk group. For the high-risk group, we propose a group sequential design with two interim analyses without toxicity monitoring. Results Based on different response rates, effect sizes, and power, required sample size and toxicity boundaries are calculated for each scenario. Sample size requirements for the designs with interim analyses are only marginally greater than the ones without. In addition, for both the intermediate-risk group and the high-risk group, conducting two interim analyses have identical required sample size compared with just one interim analysis. Additional issues that could potentially impact the trial are discussed. Conclusions We recommend using composite endpoints, with binary outcome for those in Stages 3, 4 and 5 with a power of 90% to detect an improvement of 20% in response rate, and 30 days mortality rate outcome for those in Stages 6 and 7 with a power of 90% to detect 15% (effect size) reduced mortality rate, in the COVID-19 trial design. For the intermediate-risk group, two interim analyses for efficacy evaluation along with toxicity monitoring are encouraged. For the high-risk group, two interim analyses without toxicity monitoring is advised.

Membranous glomerulonephritis

2018 ◽  
Author(s):  
Daniel C. Cattran ◽  
Heather N. Reich
Keyword(s):  
Glomerular Filtration Rate ◽  
High Risk ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Risk Group ◽  
Membranous Glomerulonephritis ◽  
High Risk Group ◽  
Randomized Studies ◽  
Medium Risk

A common rule of thumb in primary membranous glomerulonephritis (MGN) is that one-third of patients improve spontaneously, one-third progress, and one-third continue to have substantial proteinuria. The rate of spontaneous recovery may be near the truth, but MGN is usually an indolent condition and few studies have run long enough to give accurate outcomes for the remainder. However MGN is an important cause of end-stage renal failure. Treatment regimens that include cyclophosphamide or chlorambucil can improve the outcome of patients at greatest risk of deterioration, but their toxicity has limited their use in randomized studies to the highest risk patients. Steroids alone, and ciclosporin, do not improve long-term outcomes in these studies. Whether anti-B-cell antibodies offer additional benefits requires randomized studies. After confirming the diagnosis of primary MGN it is recommended to maximize supportive therapy and monitor for at least 6 months to give a clear picture of the long-term risk. For patients at lowest risk, supportive management and monitoring alone is recommended. Patients at medium risk (nephrotic range proteinuria but normal and stable glomerular filtration rate), or high risk (very heavy proteinuria, greater than 8 g/day or deterioration of glomerular filtration rate) may justify specific treatment directed at the immune response. For the medium-risk group it is not certain that it is required; for some in the high-risk group it may come too late. Overall outcomes in the high-risk group remain quite poor even with aggressive treatment.

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