Impact of unequal censoring and insufficient follow-up on comparing survival outcomes: Applications to clinical studies

2021 ◽  
pp. 096228022110175
Author(s):  
Deo Kumar Srivastava ◽  
E Olusegun George ◽  
Zhaohua Lu ◽  
Shesh N Rai
Keyword(s):  
Clinical Trials ◽  
Cardiovascular Events ◽  
Survival Outcomes ◽  
Simulation Studies ◽  
Extensive Simulation ◽  
Statistical Procedures ◽  
Survival Endpoints ◽  
Lost To Follow Up ◽  
The Impact

Clinical trials with survival endpoints are typically designed to enroll patients for a specified number of years, (usually 2–3 years) with another specified duration of follow-up (usually 2–3 years). Under this scheme, patients who are alive or free of the event of interest at the termination of the study are censored. Consequently, a patient may be censored due to insufficient follow-up duration or due to being lost to follow-up. Potentially, this process could lead to unequal censoring in the treatment arms and lead to inaccurate and adverse conclusions about treatment effects. In this article, using extensive simulation studies, we assess the impact of such censorings on statistical procedures (the generalized logrank tests) for comparing two survival distributions and illustrate our observations by revisiting Mukherjee et al.’s 1 findings of cardiovascular events in patients who took Rofecoxib (Vioxx).

scholarly journals Evaluating the Efficacy of Therapies in Patients With Coronavirus Disease 2019

2020 ◽  
Author(s):  
Dan-Yu Lin ◽  
Donglin Zeng ◽  
Joseph J Eron
Keyword(s):  
Clinical Trials ◽  
Clinical Course ◽  
Clinical Status ◽  
Therapeutic Agents ◽  
Simulation Studies ◽  
Specific Change ◽  
Extensive Simulation ◽  
Clinical Events ◽  
Full Picture

Abstract There is a proliferation of clinical trials worldwide to find effective therapies for patients diagnosed with coronavirus disease 2019 (COVID-19). The endpoints that are currently used to evaluate the efficacy of therapeutic agents against COVID-19 are focused on clinical status at a particular day or on time to a specific change of clinical status. To provide a full picture of the clinical course of a patient and make complete use of available data, we consider the trajectory of clinical status over the entire follow-up period. We also show how to combine the evidence of treatment effects on the occurrences of various clinical events. We compare the proposed and existing endpoints through extensive simulation studies. Finally, we provide guidelines on establishing the benefits of treatments.

scholarly journals The relationship between diastolic blood pressure and the risk of cardiovascular events in patients with atrial fibrillation: the Fushimi AF registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Ikeda ◽  
M Iguchi ◽  
H Ogawa ◽  
Y Aono ◽  
K Doi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Cardiovascular Events ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
The Impact

Abstract Background Hypertension is one of the major risk factors of cardiovascular events in patients with atrial fibrillation (AF). However, relationship between diastolic blood pressure (DBP) and cardiovascular events in AF patients remains unclear. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. Follow-up data were available in 4,466 patients, and 4,429 patients with available data of DBP were examined. We divided the patients into three groups; G1 (DBP<70 mmHg, n=1,946), G2 (70≤DBP<80, n=1,321) and G3 (80≤DBP, n=1,162), and compared the clinical background and outcomes between groups. Results The proportion of female was grater in G1 group, and the patients in G1 group were older and had higher prevalence of heart failure (HF), diabetes mellitus (DM), chronic kidney disease (CKD). Prescription of beta blockers was higher in G1 group, but that of renin-angiotensin system-inhibitors and calcium channel blocker was comparable. During the median follow-up of 1,589 days, in Kaplan-Meier analysis, the incidence rates of cardiovascular events (composite of cardiac death, ischemic stroke and systemic embolism, major bleeding and HF hospitalization during follow up) were higher in G1 group and G3 group than G2 group (Figure 1). When we divided the patients based on the systolic blood pressure (SBP) at baseline (≥130 mmHg or <130 mmHg), the incidence of rates of cardiovascular events were comparable among groups. Multivariate Cox proportional hazards regression analysis including female gender, age (≥75 years), higher SBP (≥130 mmHg), DM, pre-existing HF, CKD, low left ventricular ejection fraction (<40%) and DBP (G1, G2, G3) revealed that DBP was an independent determinant of cardiovascular events (G1 group vs. G2 group; hazard ratio (HR): 1.40, 95% confidence intervals (CI): 1.19–1.64, G3 group vs. G2 group; HR: 1.23, 95% CI: 1.01–1.49). When we examined the impact of DBP according to 10 mmHg increment, patients with very low DBP (<60 mmHg) (HR: 1.50,95% CI:1.24–1.80) and very high DBP (≥90 mmHg) (HR: 1.51,95% CI:1.15–1.98) had higher incidence of cardiovascular events than patients with DBP of 70–79 mmHg (Figure 2). However, when we examined the impact of SBP according to 20 mmHg increment, SBP at baseline was not associated with the incidence of cardiovascular events (Figure 3). Conclusion In Japanese patients with AF, DBP exhibited J curve association with higher incidence of cardiovascular events. Funding Acknowledgement Type of funding source: None

scholarly journals A Review of Marital Intimacy-Enhancing Interventions among Married Individuals

2015 ◽  
Vol 8 (8) ◽  
pp. 74 ◽  
Author(s):  
Maryam Kardan-Souraki ◽  
Zeinab Hamzehgardeshi ◽  
Ismail Asadpour ◽  
Reza Ali Mohammadpour ◽  
Soghra Khani
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trials ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Main Concern ◽  
Care Providers ◽  
Marital Intimacy ◽  
Randomized Controlled ◽  
The Impact

<p><strong>BACKGROUND:</strong> Lack of intimacy is currently the main concern rather than main concern of the experts in psychology and counseling. It is considered as one of the most important causes for divorce and as such to improve marital intimacy a great number of interventions have been proposed in the literature. Intimacy training and counseling make the couples take effective and successful steps to increase marital intimacy. No study has reviewed the interventions promoting marital intimacy after marriage. Thus, this review study aimed to classify the articles investigating the impact of interventional programs on marital intimacy after marriage.</p><p><strong>SEARCH METHODS:</strong> In April 2015, we performed a general search in Google Scholar search engines, and then we did an advanced search the databases of Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, <a href="http://www.cochranelibrary.com/">Cochrane Library</a>, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL). Also, lists of the references of the relevant articles were reviewed for additional citations. Using Medical Subject Headings (MESH) keywords: Intervention (Clinical Trials, Non-Randomized Controlled Trials, Randomized Controlled Trials, Education), intimacy, marital (Marriage) and selected related articles to the study objective were from 1995 to April 2015. Clinical trials that evaluated one or more behavioral interventions to improve marital intimacy were reviewed in the study.</p><p><strong>MAIN RESULTS:</strong> 39 trials met the inclusion criteria. Eleven interventions had follow-up, and 28 interventions lacked follow-up. The quality evidence for 22 interventions was low, for 15 interventions moderate, and for one intervention was considered high. Findings from studies were categorized in 11 categories as the intimacy promoting interventions in dimensions of emotional, psychological, physical, sexual, temporal, communicational, social and recreational, aesthetic, spiritual, intellectual intimacy, and total intimacy.</p><p><strong>AUTHORS’ CONCLUSIONS:</strong> Improving and promoting communication, problem solving, self-disclosure and empathic response skills and sexual education and counseling in the form of cognitive-behavioral techniques and based on religious and cultural context of each society, an effective step can be taken to enhance marital intimacy and strengthen family bonds and stability. Health care providers should consider which interventions are appropriate to the couple characteristics and their relationships.</p>

scholarly journals Challenges in Tuberculosis Clinical Trials in the Face of the COVID-19 Pandemic: A Sponsor’s Perspective

2020 ◽  
Vol 5 (2) ◽  
pp. 86
Author(s):  
I.D. Rusen
Keyword(s):  
Clinical Trials ◽  
Safety Monitoring ◽  
Chain Management ◽  
Mdr Tb ◽  
The Face ◽  
System Functioning ◽  
Treatment Continuity ◽  
The Impact ◽  
Trial Participants

The COVID-19 pandemic has caused unforeseen and extreme changes in societal and health system functioning not previously experienced in most countries in a lifetime. The impact of the pandemic on clinical trials can be especially profound given their complexities and operational requirements. The STREAM Clinical Trial is the largest trial for MDR-TB ever conducted. Currently operating in seven countries, the trial had 126 participants on treatment and 312 additional participants in active follow up as of March 31, 2020. Areas of particular concern during this global emergency include treatment continuity, supply chain management and participant safety monitoring. This commentary highlights some of the challenges faced due to the pandemic and the steps taken to protect the safety of trial participants and the integrity of the trial.

Opt-out screening for HIV, hepatitis B and hepatitis C: observational study of screening acceptance, yield and treatment outcomes

2019 ◽  
Vol 37 (2) ◽  
pp. 102-105 ◽  
Author(s):  
Conor Grant ◽  
Sarah O'Connell ◽  
Darren Lillis ◽  
Anne Moriarty ◽  
Ian Fitzgerald ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Hepatitis B ◽  
Screening Programme ◽  
Linkage To Care ◽  
Opt Out ◽  
B Virus ◽  
Lost To Follow Up ◽  
The Impact ◽  
Test Result

BackgroundWe initiated an emergency department (ED) opt-out screening programme for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) at our hospital in Dublin, Ireland. The objective of this study was to determine screening acceptance, yield and the impact on follow-up care.MethodsFrom July 2015 through June 2018, ED patients who underwent phlebotomy and could consent to testing were tested for HIV, HBV and HCV using an opt-out approach. We examined acceptance of screening, linkage to care, treatment and viral suppression using screening programme data and electronic health records. The duration of follow-up ranged from 1 to 36 months.ResultsOver the 36-month study period, there were 140 550 ED patient visits, of whom 88 854 (63.2%, 95% CI 63.0% to 63.5%) underwent phlebotomy and 54 817 (61.7%, 95% CI 61.4% to 62.0%) accepted screening for HIV, HBV and HCV, representing 41 535 individual patients. 2202 of these patients had a positive test result. Of these, 267 (12.1%, 95% CI 10.8% to 13.6%) were newly diagnosed with an infection and 1762 (80.0%, 95% CI 78.3% to 81.7%) had known diagnoses. There were 38 new HIV, 47 new HBV and 182 new HCV diagnoses. 81.5% (95% CI 74.9% to 87.0%) of known patients who were not linked were relinked to care after screening. Of the new diagnoses, 86.2% (95% CI 80.4 to 90.8%) were linked to care.ConclusionAlthough high proportions of patients had known diagnoses, our programme was able to identify many new infected patients and link them to care, as well as relink patients with known diagnoses who had been lost to follow-up.

scholarly journals Association of Cardiovascular Risk Factors With Cardiac Events and Survival Outcomes Among Patients With Breast Cancer Enrolled in SWOG Clinical Trials

2018 ◽  
Vol 36 (26) ◽  
pp. 2710-2717 ◽  
Author(s):  
Dawn L. Hershman ◽  
Cathee Till ◽  
Sherry Shen ◽  
Jason D. Wright ◽  
Scott D. Ramsey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Overall Survival ◽  
Clinical Trials ◽  
Survival Outcomes ◽  
Cardiac Events ◽  
Free Survival ◽  
Increased Risk

Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.

Acute Promyelocytic Leukemia In Canada: Poor Outcomes In Older Patients Remain

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1714-1714
Author(s):  
Matthew D. Seftel ◽  
Anna Serebrin ◽  
Pascal Lambert ◽  
Julie Bergeron ◽  
Janeve Everett ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Acute Promyelocytic Leukemia ◽  
Older Patients ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Survival Outcomes ◽  
Younger Patients ◽  
One Year

Abstract Introduction Despite widespread use of all-trans retinoic acid (ATRA) in treatment of Acute Promyelocytic Leukemia (APL), recent studies in the US1 and Sweden2 have reported continuing high rates of early death. Patient age has appeared to be an important factor affecting outcomes. We studied the incidence and outcomes in the Canadian APL patients to determine which patients may be at higher risk, and to analyze the success of current management. Methods We used data from the Canadian Cancer Registry, which included all patients diagnosed between 1993-2007. We obtained incidence, Early Death (ED) (death within 30 days of diagnosis), and 1 and 5-year overall survival (OS). This was stratified by age, sex, and time period of diagnosis. Detailed information was obtained on a subset of patients managed at five Canadian leukemia referral centres from 1999 to 2010. Results There were 399 cases of APL diagnosed in Canada between 1993-2007.This accounted for 3.01% of Acute Myeloid Leukemia cases. Incidence (age-standardized to the 1991 Canadian census population) was 0.083/100000. The incidence was greater in the population aged 50 and over, with an incidence rate ratio (IRR) of 2.192 (95% C.I.1.80 - 2.67, p<0.001). ED was 21.8% overall, with a rate over three times higher in older patients as compared to younger patients. The ED rate was 10.6% in younger (<50 years) patients and 35.5% in older (≥50 years) patients. One-year overall survival was 84.1% in younger patients as compared to 52.3% in older adults. The rate of death at one year is nearly three times higher in the older patients. Five-year survival was 54.6%; this was 73.3% in the younger patients (<50), and 29.1% in the older group (≥50 years). There were 131 patients in the leukemia referral centre cohort, who predominantly received tretinoin (ATRA) based therapy. In this population, ED was 14.6%. Two-year OS was 76.5% (95% C.I. 68%-83%). Age over 60 predicted an inferior outcome at 2-years with a hazard ratio of 4.051 (95% CI 1.17-7.57). Conclusions To our knowledge, this is the largest nationwide epidemiologic study of APL. Despite widespread use of ATRA in Canada and low rates of ED reported in clinical trials (often 3-8%), we found that the real survival outcomes of APL were worse than anticipated. However they were similar to those reported recently from other developed counties1,2. The outcomes were much poorer for the older patients with APL. This included a higher rate of early death as well as poorer rates of survival at one, two and five year follow-up times. The ED rates of patients <50 more closely matched rates reported in clinical trials. We compared the survival outcomes of the entire population with APL to a sample of only patients treated at specialized referral centres. Despite receiving care in a specialized tertiary centre, the survival of older patients remained significantly poorer than the younger patients. The incidence of APL was also double in the older population as compared to the younger population. Overall the age-standardized incidence was lower in Canada than has been reported in other countries1,2. This emphasizes that, although APL is a type of AML that does affect younger patients, there is a large and important impact of this disease on older patients. Recent studies in the US and Sweden have also reported higher rates of APL in older populations and poorer rates of survival at various follow up times. Overall the patients with high-risk Sanz scores had the worst survival outcomes. The survival at most time points was slightly higher for patients scored as intermediate-risk compared to those who were in the low-risk category. When arsenic becomes widely available as a first line therapy it will be important to continue population-based analysis to see how this affects outcomes and whether the outcomes are difference in difference age groups or populations. Disclosures: No relevant conflicts of interest to declare.

Risk of arterial (ATE) and venous thromboembolism (VTE) in a population-based cohort of bevacizumab-treated metastatic colorectal cancer (mCRC) patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 545-545 ◽  
Author(s):  
Irene S. Yu ◽  
Winson Y. Cheung
Keyword(s):  
Clinical Trials ◽  
Population Based ◽  
Related Effect ◽  
Related Factors ◽  
Increased Risk ◽  
Venous Thromboembolic ◽  
Lost To Follow Up ◽  
Study Setting ◽  
Trial Setting

545 Background: Bevacizumab is associated with both arterial (ATE) and venous thromboembolic (VTE) events, estimated to be </=15% from clinical trials. Our objectives were to 1) characterize the incidence of ATE or VTE among mCRC patients receiving bevacizumab in a non-clinical trial setting; 2) determine patient and treatment-related factors that predispose to an increased risk of ATE or VTE; and 3) explore how thromboembolism is managed and whether bevacizumab is discontinued and/or resumed after an event. Methods: A random sample of mCRC patients diagnosed between 2008 and 2009, referred to 1 of 5 regional cancer centers in British Columbia, and who were offered bevacizumab was reviewed. Summary statistics were used to describe and compare clinical factors between those who experienced an ATE or VTE and those who did not. Results: Of the 200 mCRC patients offered bevacizumab, 10 never received the drug and 12 were lost to follow up. Among the 178 remaining patients, median age was 61 years, 103 (58%) were male, and 121 (85%) had ECOG 0 to 1. A total of 39 patients (28%) experienced at least 1 documented thromboembolic event. Compared to patients who developed a clot, those who did not had similar median age (62 vs 61), gender distribution (23% men and 20% women), ECOG 0 to 1 (84% vs 85%) and body mass index (26.4 vs 25.3). However, the mean number of bevacizumab doses was higher in the group with thromboembolism (12.6 vs 9.0), suggesting a potential dose-related effect. There were a total of 43 VTE and 5 ATE events documented, with 7 of the 39 patients (18%) experiencing more than 1 event. Bevacizumab was held or discontinued in 60% of cases, but it was continued in 25% of the cases; 4% of the events were fatal, and 10% of the VTE/ATE occurred after bevacizumab was stopped. Conclusions: The incidence of ATE and VTE in a non-study setting appears to be higher than that reported in clinical trials. There may be a dose-related effect. Bevacizumab was not consistently held or discontinued in the setting of a VTE or ATE. Development of guidelines for the management of thromboembolism with bevacizumab may be warranted.

Integrating clinical pharmacy services into patient care in an early-phase clinical trial clinic.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18228-e18228
Author(s):  
Dazhi Liu ◽  
Thu Oanh Dang ◽  
Stephen Harnicar ◽  
Katherine Kargus ◽  
Lauren A Evans ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Supportive Care ◽  
Clinical Pharmacist ◽  
Early Phase ◽  
Treatment Options ◽  
Cancer Center ◽  
Protocol Violation ◽  
Patients With Cancer ◽  
The Impact

e18228 Background: Early phase clinical trials have broadened treatment options for patients with cancer. Expert management of these new therapies is essential to positive patient outcomes. At Memorial Sloan Kettering Cancer Center, the Developmental Therapeutic Center (DTC) satisfies this need. Oncology clinical pharmacists collaborate with other healthcare professionals to maximize the benefits of drug therapy and minimize toxicities. The purpose of this project is to describe the interventions from a clinical pharmacist assigned to the DTC. Methods: A clinical pharmacist joined DTC to serve adult patients with cancer undergoing clinical trials. The clinical pharmacist acted as a liaison between pharmacy team and medical team, and sees patients during their trial eligibility screening and follow-up visits. The interventions were documented by the clinical pharmacist in patients’ medical charts and email communications. All interventions during 1 month were retrospectively collected and categorized into supportive care optimization, protocol violation prevention, and operational. Results: The oncology clinical pharmacist was involved in 115 patient visits for trial eligibility screening or protocol follow-up. A total of 769 interventions were addressed including supportive care optimization (40.2%), protocol violation prevention (24.7%), and operational (35.1%). Conclusions: The oncology clinical pharmacist is actively engaged in many aspects of cancer care at the early phase trial clinic. Our results demonstrate the vital role of an oncology clinical pharmacist. The impact of these categorized intervention areas would require a formal outcome and cost-saving analysis. [Table: see text]

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