Observation of Time-Dependent Adverse Events and the Influence of Drop-Out Thereon in Long-Term Safety Studies—Simulation Study Under the Current Practice of Post-marketing Safety Evaluation in Japan

2004 ◽  
Vol 14 (2) ◽  
pp. 403-414 ◽  
Author(s):  
Mamoru Narukawa ◽  
Akifumi Yafune ◽  
Masahiro Takeuchi
Keyword(s):  
Adverse Events ◽  
Simulation Study ◽  
Current Practice ◽  
Safety Evaluation ◽  
Drop Out ◽  
Time Dependent ◽  
Safety Studies ◽  
Post Marketing

Safety and tolerability of prescribed usage of Derise® (Darbepoetin Alfa, Hetero) in symptomatic anemia: A Post Marketing Surveillance Study

2020 ◽  
Author(s):  
Shubhadeep Sinha ◽  
Vamsi Krishna Bandi ◽  
Bala Reddy Bheemareddy ◽  
Pankaj Thakur ◽  
Sreenivasa Chary ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Adverse Events ◽  
Darbepoetin Alfa ◽  
P Value ◽  
End Of Treatment ◽  
Post Marketing Surveillance ◽  
Post Marketing

Abstract Background This post marketing surveillance, observational, prospective, safety study evaluated the safety, tolerability and long term immunogenicity of prescribed usage of Darbepoetin alfa, (DA-α, manufactured by Hetero Biopharma) in Indian patients with chronic kidney disease with anemia.Methods All patients with anemia of chronic kidney disease prescribed Hetero-Darbepoetin were the target patient population. The present study gathered the data from 503 Hetero-Darbepoetin alfa prescribed patients. This study collected information of patient demography, patient's medical history, concomitant medications, action taken with respect to Hetero-Darbepoetin-alfa, AE details (AE term, start date, stop date, severity, action taken, outcome and causality), periodic Hemoglobin (Hb) levels and abnormal laboratory tests results until treatment is discontinued or the patient is lost to follow-up. Immunogenicity data was collected in 121 patients at the end of treatment and after 1 year. Statistical analyses were performed to explore and analyze details of individual case safety reports of adverse events such as incidence, severity, seriousness, outcome, duration, action taken, and causality relationship of individual adverse event (AE) to the prescribed study drug. Results 87 AEs were reported in this study and most of them were mild to moderate in intensity. No deaths or serious adverse events (SAEs) were reported in this study. Anti-drug antibodies were not detected in any subject at the end of treatment phase and after 12 months long term follow up period. Baseline mean Hemoglobin value was 8.34 (SD 1.24) g/dL and last visit mean Hemoglobin value was 10.42 (SD 1.28) g/dL. The mean difference between baseline and last visit was 2.10 [2.00, 2.20], statistically significant (p-value <.0001). Conclusions The safety and tolerability of the usage of DA-α (manufactured by Hetero Biopharma) is similar to that reported in the published literature of the innovator. No patients showed anti-drug antibodies after treatment. Additionally, the patients also showed significant improvement in hemoglobin levels, compared to baseline.Clinical Trial Registry Number: CTRI/2017/04/008338 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/login.php : 12/04/2017]; Trial Registered Retrospectively

scholarly journals Comparing Current and Emerging Practice Models For the Extrapolation of Survival Data: A Simulation Study and Case-Study

2021 ◽  
Author(s):  
Benjamin Kearns ◽  
Matt D. Stevenson ◽  
Kostas Triantafyllopoulos ◽  
Andrea Manca
Keyword(s):  
Simulation Study ◽  
Current Practice ◽  
Additive Models ◽  
Survival Models ◽  
Sample Sizes ◽  
Practice Models ◽  
Long Term Follow Up

Abstract BackgroundEstimates of future survival can be a key evidence source when deciding if a medical treatment should be funded. Current practice is to use standard parametric models for generating extrapolations. Several emerging, more flexible, survival models are available which can provide improved within-sample fit. This study aimed to assess if these emerging practice models also provided improved extrapolations.MethodsBoth a simulation study and a case-study were used to assess the goodness of fit of five classes of survival model. These were: current practice models, Royston Parmar models (RPMs), Fractional polynomials (FPs), Generalised additive models (GAMs), and Dynamic survival models (DSMs). The simulation study used a mixture-Weibull model as the data-generating mechanism with varying lengths of follow-up and sample sizes. The case-study was long-term follow-up of a prostate cancer trial. For both studies, models were fit to an early data-cut of the data, and extrapolations compared to the known long-term follow-up.ResultsThe emerging practice models provided better within-sample fit than current practice models. For data-rich simulation scenarios (large sample sizes or long follow-up), the GAMs and DSMs provided improved extrapolations compared with current practice. Extrapolations from FPs were always very poor whilst those from RPMs were similar to current practice. With short follow-up all the models struggled to provide useful extrapolations. In the case-study all the models provided very similar estimates, but extrapolations were all poor as no model was able to capture a turning-point during the extrapolated period. ConclusionsGood within-sample fit does not guarantee good extrapolation performance. Both GAMs and DSMs may be considered as candidate extrapolation models in addition to current practice. Further research into when these flexible models are most useful, and the role of external evidence to improve extrapolations is required.

scholarly journals Tolerability of Omalizumab in Asthma as a Major Compliance Factor: 10-Year Follow Up

2018 ◽  
Vol 6 (10) ◽  
pp. 1839-1844 ◽  
Author(s):  
Mona Al-Ahmad ◽  
Jasmina Nurkic ◽  
Ahmed Maher ◽  
Nermina Arifhodzic ◽  
Edin Jusufovic
Keyword(s):  
Adverse Events ◽  
Treatment Efficacy ◽  
Real Life ◽  
Drop Out ◽  
Uncontrolled Asthma ◽  
Increased Risk ◽  
Asthma Patients ◽  
Severe Adverse Events

BACKGROUND: There is a lack of data related to real life, long-term safety, tolerability and compliance of omalizumab treatment in asthma patients beyond 6 years. AIM: Study aimed to assess safety, tolerability, compliance and all reasons for treatment discontinuation during 10 years on omalizumab. SUBJECT AND METHODS: This is a retrospective, observational study of uncontrolled asthma patients receiving omalizumab for the last 10 years. All data were collected from patients’ files (demographics, adverse events, comorbidities, compliance index, reasons for discontinuation of omalizumab). Reactions to omalizumab were classified as local and systemic, and their severity as mild, moderate or severe. Reactions were either immediate (minutes to hours after drug administration) or delayed (after days). Compliance to omalizumab, defined as Compliance index (CI), was calculated by comparing milligrams of given to milligrams of prescribed dose/ per year. RESULTS: Out of 35 patients receiving omalizumab, 15 drop out at different time points mostly due to treatment efficacy or appearance of new comorbidities. Patients who continue for the next ten years had mild to moderate adverse events related to omalizumab. There was no increased risk of severe adverse events during 10 years on omalizumab. Patient’s treatment tolerability, despite mild to moderate adverse events, is in favour of compliance. CONCLUSION: Compliance with omalizumab mildly decreased over 10 years but was not affected by severe adverse events of treatment or new comorbidities. Although, omalizumab is safe medicine appearance of new comorbidities has to be closely followed up.

scholarly journals Comparing current and emerging practice models for the extrapolation of survival data: a simulation study and case-study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Benjamin Kearns ◽  
Matt D. Stevenson ◽  
Kostas Triantafyllopoulos ◽  
Andrea Manca
Keyword(s):  
Simulation Study ◽  
Current Practice ◽  
Additive Models ◽  
Survival Models ◽  
Sample Sizes ◽  
Practice Models ◽  
Long Term Follow Up

Abstract Background Estimates of future survival can be a key evidence source when deciding if a medical treatment should be funded. Current practice is to use standard parametric models for generating extrapolations. Several emerging, more flexible, survival models are available which can provide improved within-sample fit. This study aimed to assess if these emerging practice models also provided improved extrapolations. Methods Both a simulation study and a case-study were used to assess the goodness of fit of five classes of survival model. These were: current practice models, Royston Parmar models (RPMs), Fractional polynomials (FPs), Generalised additive models (GAMs), and Dynamic survival models (DSMs). The simulation study used a mixture-Weibull model as the data-generating mechanism with varying lengths of follow-up and sample sizes. The case-study was long-term follow-up of a prostate cancer trial. For both studies, models were fit to an early data-cut of the data, and extrapolations compared to the known long-term follow-up. Results The emerging practice models provided better within-sample fit than current practice models. For data-rich simulation scenarios (large sample sizes or long follow-up), the GAMs and DSMs provided improved extrapolations compared with current practice. Extrapolations from FPs were always very poor whilst those from RPMs were similar to current practice. With short follow-up all the models struggled to provide useful extrapolations. In the case-study all the models provided very similar estimates, but extrapolations were all poor as no model was able to capture a turning-point during the extrapolated period. Conclusions Good within-sample fit does not guarantee good extrapolation performance. Both GAMs and DSMs may be considered as candidate extrapolation models in addition to current practice. Further research into when these flexible models are most useful, and the role of external evidence to improve extrapolations is required.

Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance

2013 ◽  
Vol 45 (6) ◽  
pp. 469-477 ◽  
Author(s):  
Takashi Nakano ◽  
Akihisa Okumura ◽  
Takuya Tanabe ◽  
Shimpei Niwa ◽  
Masato Fukushima ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Evaluation ◽  
Post Marketing

Office-based post-marketing surveillance study on the influence of long term therapy with aripiprazole in patients with schizophrenia

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
M Kungel ◽  
A Engelhardt ◽  
T Spevakné-Göröcs ◽  
M Ebrecht ◽  
C Werner ◽  
...  
Keyword(s):  
Surveillance Study ◽  
Term Therapy ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Long Term Therapy

Effectiveness of Classification Measures in Predicting Achievement in the Israel Defence Forces - Fitness Instruction Trainers Courses as a Case Study

2012 ◽  
Vol 21 (5-6) ◽  
pp. 145-172
Author(s):  
Yair Galily ◽  
Orly Kayam ◽  
Michael Bar-Eli
Keyword(s):  
Training System ◽  
Drop Out ◽  
Validity And Reliability ◽  
Screening Process ◽  
Training Course ◽  
Drop Out Rate ◽  
Army Service ◽  
Israeli Army ◽  
Israel Defense Forces

Abstract Human resources are the most crucial element in the selection of suitable fitness instruction trainers (FIT) and the results of the screening process impact greatly on the entire physical training system in the Israeli army, both in the short-term and the long-term (potential officers, young officers and developing and veteran officers). The aim of the current study is to examine the effectiveness, validity and reliability of the screening process for acceptance to the female fitness instructors training course in the Israel Defense Forces (IDF). The screening process aims to identify those that are most suitable from a large pool of candidates, in order to ensure the highest possible level of candidates and the lowest possible drop-out rate from the training course and subsequent army service. The paper examines the reliability of the classification exam currently administered in the course and its validity in predicting those candidates who will succeed in the course and in their assignments afterwards. The sample is based on a data analysis of nine screening dates over three years (three each year). The evaluation of validity is based on the relationship between the course entrance exam grades (administered a year before enlistment), exam grades at the beginning of the course and additional data relating to success in the field.

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