scholarly journals Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project

JMIR Cancer ◽  
2016 ◽  
Vol 2 (2) ◽  
pp. e16 ◽  
Author(s):  
Raymond P Perez ◽  
Shanda Finnigan ◽  
Krupa Patel ◽  
Shanell Whitney ◽  
Annemarie Forrest
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Safety ◽  
Safety Reporting ◽  
New Drug ◽  
Reporting Recommendations

scholarly journals Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

2017 ◽  
Vol 14 (3) ◽  
pp. 225-233 ◽  
Author(s):  
Raymond Perez ◽  
Patrick Archdeacon ◽  
Nancy Roach ◽  
Robert Goodwin ◽  
Jonathan Jarow ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patient Safety ◽  
Drug Administration ◽  
Drug Safety ◽  
Food And Drug Administration ◽  
Educational Materials ◽  
Research Staff ◽  
Safety Reporting ◽  
New Drug ◽  
Final Rule

Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of reports and increased sponsor communication. Sponsors replied that their greatest challenges include (1) lack of global harmonization in reporting rules, (2) determining causality, and (3) fear of regulatory repercussions. Interaction with the Food and Drug Administration has helped improve sponsors’ adherence to the final rule, and sponsors would benefit from increased communication with the Food and Drug Administration and educational materials. Conclusion: The goal of the final rule is to minimize uninformative safety reports so that important safety signals can be captured and communicated early enough in a clinical program to make changes that help ensure patient safety. Investigative staff and sponsors acknowledge that the rule has not been fully implemented although they agree with the intention. Clinical Trials Transformation Initiative will use the results from the surveys and interviews to develop new recommendations and educational materials that will be available to sponsors to increase compliance with the final rule and facilitate discussion between sponsors, investigators, and Food and Drug Administration representatives.

scholarly journals Awareness and Opinions of Research Professionals on India's New Drug and Clinical Trials Regulations: Protocol for a Cross-Sectional Web-Based Survey Study

10.2196/14744 ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. e14744
Author(s):  
Vishal Vennu ◽  
Saurabh Dahiya
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
New Drugs ◽  
Survey Study ◽  
Multiple Sources ◽  
Cross Sectional ◽  
Web Based ◽  
Google Docs ◽  
New Drug ◽  
Research Professionals

Background Although several studies have been conducted and several articles have been published on India's new clinical trial regulations, very few have examined the views of investigators and ethics board members regarding modifications to the previous regulations. Overall, they have neglected to find out the opinions of other relevant professionals, such as research assistants, coordinators, associates, and managers. To our knowledge, no study has yet investigated the awareness and opinions of Indian research professionals on the new 2019 regulations. Objective This study aims to describe the awareness and opinions of Indian research professionals on the new drug and clinical trial regulations. Methods In this cross-sectional, Web-based study, we will conduct an open survey for various Indian research professionals. These professionals will be selected randomly using multiple sources. The survey questionnaires, which have already been validated, were developed using the form function in Google docs. A Web link was generated for participants to take the survey. Descriptive statistics will be shown as means and standard deviations for constant variables, whereas certain variables will instead be shown as numbers and percentages. Results The survey was opened in July 2019. Enrollment has already started and will be completed in three months. The results calculations are expected to begin in October 2019. Conclusions The results of the survey are expected to represent the views of research professionals on the new regulations that will support the development of clinical research and the pharmaceutical industry in India. These regulations are expected to help advance clinical trials, help with the approval of new drugs, and enhance ethical norms in the country. International Registered Report Identifier (IRRID) PRR1-10.2196/14744

scholarly journals Two-stage Bayesian hierarchical modeling for blinded and unblinded safety monitoring in randomized clinical trials

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Junhao Liu ◽  
Jo Wick ◽  
Renee’ H. Martin ◽  
Caitlyn Meinzer ◽  
Dooti Roy ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Safety ◽  
Safety Data ◽  
Safety Monitoring ◽  
Safety Signal ◽  
Two Stage ◽  
Bayesian Hierarchical ◽  
Potential Safety ◽  
Stage 1

Abstract Background Monitoring and reporting of drug safety during a clinical trial is essential to its success. More recent attention to drug safety has encouraged statistical methods development for monitoring and detecting potential safety signals. This paper investigates the potential impact of the process of the blinded investigator identifying a potential safety signal, which should be further investigated by the Data and Safety Monitoring Board with an unblinded safety data analysis. Methods In this paper, two-stage Bayesian hierarchical models are proposed for safety signal detection following a pre-specified set of interim analyses that are applied to efficacy. At stage 1, a hierarchical blinded model uses blinded safety data to detect a potential safety signal and at stage 2, a hierarchical logistic model is applied to confirm the signal with unblinded safety data. Results Any interim safety monitoring analysis is usually scheduled via negotiation between the trial sponsor and the Data and Safety Monitoring Board. The proposed safety monitoring process starts once 53 subjects have been enrolled into an eight-arm phase II clinical trial for the first interim analysis. Operating characteristics describing the performance of this proposed workflow are investigated using simulations based on the different scenarios. Conclusions The two-stage Bayesian safety procedure in this paper provides a statistical view to monitor safety during the clinical trials. The proposed two-stage monitoring model has an excellent accuracy of detecting and flagging a potential safety signal at stage 1, and with the most important feature that further action at stage 2 could confirm the safety issue.

scholarly journals Awareness and Opinions of Research Professionals on India's New Drug and Clinical Trials Regulations: Protocol for a Cross-Sectional Web-Based Survey Study (Preprint)

2019 ◽  
Author(s):  
Vishal Vennu ◽  
Saurabh Dahiya
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
New Drugs ◽  
Survey Study ◽  
Multiple Sources ◽  
Cross Sectional ◽  
Web Based ◽  
Google Docs ◽  
New Drug ◽  
Research Professionals

BACKGROUND Although several studies have been conducted and several articles have been published on India's new clinical trial regulations, very few have examined the views of investigators and ethics board members regarding modifications to the previous regulations. Overall, they have neglected to find out the opinions of other relevant professionals, such as research assistants, coordinators, associates, and managers. To our knowledge, no study has yet investigated the awareness and opinions of Indian research professionals on the new 2019 regulations. OBJECTIVE This study aims to describe the awareness and opinions of Indian research professionals on the new drug and clinical trial regulations. METHODS In this cross-sectional, Web-based study, we will conduct an open survey for various Indian research professionals. These professionals will be selected randomly using multiple sources. The survey questionnaires, which have already been validated, were developed using the form function in Google docs. A Web link was generated for participants to take the survey. Descriptive statistics will be shown as means and standard deviations for constant variables, whereas certain variables will instead be shown as numbers and percentages. RESULTS The survey was opened in July 2019. Enrollment has already started and will be completed in three months. The results calculations are expected to begin in October 2019. CONCLUSIONS The results of the survey are expected to represent the views of research professionals on the new regulations that will support the development of clinical research and the pharmaceutical industry in India. These regulations are expected to help advance clinical trials, help with the approval of new drugs, and enhance ethical norms in the country. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/14744

scholarly journals Expedited Safety Reporting Through an Alert System for Clinical Trial Management at an Academic Medical Center: Retrospective Design Study (Preprint)

2019 ◽  
Author(s):  
Yu Rang Park ◽  
HaYeong Koo ◽  
Young-Kwang Yoon ◽  
Sumi Park ◽  
Young-Suk Lim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
High Risk ◽  
Performance Indicators ◽  
Phase 1 ◽  
Low Risk ◽  
Alert System ◽  
Trial Management ◽  
Safety Reporting ◽  
Clinical Trial Management

BACKGROUND Early detection or notification of adverse event (AE) occurrences during clinical trials is essential to ensure patient safety. Clinical trials take advantage of innovative strategies, clinical designs, and state-of-the-art technologies to evaluate efficacy and safety, however, early awareness of AE occurrences by investigators still needs to be systematically improved. OBJECTIVE This study aimed to build a system to promptly inform investigators when clinical trial participants make unscheduled visits to the emergency room or other departments within the hospital. METHODS We developed the Adverse Event Awareness System (AEAS), which promptly informs investigators and study coordinators of AE occurrences by automatically sending text messages when study participants make unscheduled visits to the emergency department or other clinics at our center. We established the AEAS in July 2015 in the clinical trial management system. We compared the AE reporting timeline data of 305 AE occurrences from 74 clinical trials between the preinitiative period (December 2014-June 2015) and the postinitiative period (July 2015-June 2016) in terms of three AE awareness performance indicators: onset to awareness, awareness to reporting, and onset to reporting. RESULTS A total of 305 initial AE reports from 74 clinical trials were included. All three AE awareness performance indicators were significantly lower in the postinitiative period. Specifically, the onset-to-reporting times were significantly shorter in the postinitiative period (median 1 day [IQR 0-1], mean rank 140.04 [SD 75.35]) than in the preinitiative period (median 1 day [IQR 0-4], mean rank 173.82 [SD 91.07], <i>P</i>≤.001). In the phase subgroup analysis, the awareness-to-reporting and onset-to-reporting indicators of phase 1 studies were significantly lower in the postinitiative than in the preinitiative period (preinitiative: median 1 day, mean rank of awareness to reporting 47.94, vs postinitiative: median 0 days, mean rank of awareness to reporting 35.75, <i>P</i>=.01; and preinitiative: median 1 day, mean rank of onset to reporting 47.4, vs postinitiative: median 1 day, mean rank of onset to reporting 35.99, <i>P</i>=.03). The risk-level subgroup analysis found that the onset-to-reporting time for low- and high-risk studies significantly decreased postinitiative (preinitiative: median 4 days, mean rank of low-risk studies 18.73, vs postinitiative: median 1 day, mean rank of low-risk studies 11.76, <i>P</i>=.02; and preinitiative: median 1 day, mean rank of high-risk studies 117.36, vs postinitiative: median 1 day, mean rank of high-risk studies 97.27, <i>P</i>=.01). In particular, onset to reporting was reduced more in the low-risk trial than in the high-risk trial (low-risk: median 4-0 days, vs high-risk: median 1-1 day). CONCLUSIONS We demonstrated that a real-time automatic alert system can effectively improve safety reporting timelines. The improvements were prominent in phase 1 and in low- and high-risk clinical trials. These findings suggest that an information technology-driven automatic alert system effectively improves safety reporting timelines, which may enhance patient safety.

Application of Metadata Repository and Master Data Management in Clinical Trial and Drug Safety

2015 ◽  
pp. 33-46
Author(s):  
Chandrakant Ekkirala
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Data Management ◽  
Drug Safety ◽  
Detailed Explanation ◽  
Master Data ◽  
Master Data Management ◽  
Metadata Repository ◽  
Definition Of

This chapter talks about metadata repository, and master data management in clinical trial and drug safety. The chapter begins with the definition of metadata repository and gives an explanation around the same, It talks about a well designed metadata repository and the characteristics associated with the same. A brief around why we need metadata and the reasons for the using the same has also been mentioned. The benefits of a well structured metadata repository was also mentioned in detail. The chapter then gives a detailed explanation on master data management and the usage of MDM in clinical trials. MDM solutions for clinical trials management is also explained in detail.

scholarly journals PLANNING PROCESS OF PILOT BATCH PRODUCTION OF AN INNOVATIVE DRUG FOR CLINICAL TRIAL IN A PHARMACEUTICAL INDUSTRY

2016 ◽  
Vol 13 (4) ◽  
pp. 462
Author(s):  
Lila M. Harada ◽  
Adriano Manicoba Da Silva
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Production Planning ◽  
Planning Process ◽  
Scale Production ◽  
Manufacturing Plant ◽  
Innovative Drug ◽  
Batch Production ◽  
New Drug ◽  
Pilot Batch

Purpose – Clinical trials are the most critical step in the process of drug development and evaluation to bring a new drug to market. The purpose of this article was to show an approach of the planning and production of a new innovative drug for a clinical study, based on the presentation of decision-making process in a national pharmaceutical industry.Design / methodology / approach - Through a case-study methodology, it was described the pilot batch production planning of a new drug for clinical trial, focusing on how the company evaluates the adequacy of the available systems at the manufacturing plant and how they use them in drug production planning process.Findings – A previous planning for clinical trial supplies production is determinant to decide the order, amount and timing of the products to be produced when the manufacturing plant is shared with the production of commercial products. Also, even in a small pilot batch production, there is a substantial waste of supplies during the process.Research Limitations / Implications – This study showed the production planning process of one investigational product with the recruitment of few patients for the clinical trial. However, the number of patients enrolled can reach thousands in many clinical trials, and it does need a more complex production planning to avoid wastes and try to reduce the process costs.Practical Implications - This article provides a picture of the production planning of clinical trial supplies chain under uncertainty and the decisions that affect the large-scale production of commercial drugs and the pilot batch production of experimental drugs.Originality / value - Although the results of clinical trials is the most significant source of uncertainty in the development process of any new drug, a good clinical supply planning and processes management can avoid or attenuate the imminent risk of process failure. 

The impact of NCI-sponsored network group clinical trials on guideline care and new drug indications.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6604-6604
Author(s):  
Joseph M. Unger ◽  
Van T. Nghiem ◽  
Dawn L. Hershman ◽  
Riha Vaidya ◽  
Michael Leo LeBlanc ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Guidelines ◽  
Research Network ◽  
Phase Iii ◽  
Cancer Clinical Trials ◽  
New Drug ◽  
Public Data ◽  
Drug Approvals ◽  
The Impact

6604 Background: National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying new antineoplastic regimens. However, the clinical impact of their trials has not been systematically examined. We analyzed the influence of network group cancer clinical trials on clinical guidelines and new drug approvals. Methods: We evaluated Phase III cancer clinical trials which the SWOG Cancer Research Network coordinated or participated in (1980-2017). Included trials were completed and its results published. A documented practice influential (DPI) trial was one with verified influence on National Comprehensive Cancer Network (NCCN) clinical guidelines (available starting in 1996) or on U.S. Food and Drug Administration (FDA)-approved package inserts. We estimated the rate of DPI trials overall and over time. The total federal investment supporting the set of trials was also determined based on public data. Results: In total, 182 trials comprising 148,028 patients were studied. We identified 79 DPI studies (43.4%); 73 influenced NCCN guidelines, 12 influenced new drug approvals, and 6 influenced both. The rate of DPI trials was 72.3% (47/65) among formally positive trials (i.e., achieved their protocol specified endpoint) and 27.4% (32/117) among negative trials. Thus 40.5% (32/79) of DPI trials were based on negative studies, half of which (16/32 = 50.0%) reaffirmed standard of care over experimental therapy. There were no differences between DPI and non-DPI trials in key study design characteristics. Total federal investment for the programs conducting the trials was $1.36 billion (USD2017), a rate of $7.5 million per trial, or $17.2 million per DPI trial. Conclusions: Nearly half of all phase III trials by one of the NCTN’s largest groups had documented practice influence on clinical care guidelines or new drug approvals. Even many negative trials impacted guideline recommendations. Compared to the costs of a new drug approval in pharmaceutical companies – typically estimated at > $1 billion – the amount invested by federal funders to provide this valuable evidence was modest. These findings highlight the major role of the NCTN’s clinical trial program in advancing oncology practice.

scholarly journals Re-Evaluating Eligibility Criteria for Oncology Clinical Trials: Analysis of Investigational New Drug Applications in 2015

2017 ◽  
Vol 35 (33) ◽  
pp. 3745-3752 ◽  
Author(s):  
Susan Jin ◽  
Richard Pazdur ◽  
Rajeshwari Sridhara
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Patient Population ◽  
Trial Participation ◽  
Cancer Clinical Trials ◽  
Eligibility Criteria ◽  
New Drug ◽  
Drug Clinical Trial ◽  
Oncology Clinical Trials ◽  
Eligibility Requirements

Clinical trial eligibility criteria are necessary to define the patient population under study and improve trial safety. However, there are concerns that eligibility criteria for cancer clinical trials are too restrictive and limit patient enrollment in clinical trials. Recently, there have been initiatives to re-examine and modernize eligibility criteria for oncology clinical trials. To assess current eligibility requirements for cancer clinical trials, we have conducted a comprehensive review of eligibility criteria for commercial investigational new drug clinical trial applications submitted to the US Food and Drug Administration Office of Hematology and Oncology Products in 2015. Our findings suggest that eligibility criteria for current cancer clinical trials tend to narrowly define the study population and limit the study to lower-risk patients, which may not be reflective of the greater patient population outside of the study. We discuss potential areas for expanding eligibility criteria to include more patients in clinical trials and design options for clinical trials incorporating expanded eligibility criteria. The broadening of clinical trial eligibility criteria can be considered to better reflect the real-world patient population, improve clinical trial participation, and increase patient access to new investigational treatments.

scholarly journals Clinical Trial Risk in Non-Hodgkin’s Lymphoma: Endpoint and Target Selection

2011 ◽  
Vol 14 (2) ◽  
pp. 227 ◽  
Author(s):  
Jayson Lee Parker ◽  
Zoe Yi Zhang ◽  
Rena Buckstein
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Success Rate ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Secondary Outcome ◽  
Drug Candidates ◽  
New Drug ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose. To quantify the clinical trial risk of new drug development in Non-Hodgkin’s lymphoma (NHL). Risk estimates for this disease have not been reported before. Methods. We undertook a retrospective review of clinical trials in (NHL) in four subtypes to compare the success rate with the industry average. Our inclusion criteria required that a drug must initiate its phase I trial in one of the four NHL subtypes between 1998 and June 2008 in the US. In addition, clinical trials of new drug candidates that pertain to four subtypes of NHL were retrieved from clinicaltrial.gov. Drug candidates that did not meet these criteria were excluded from the study. Results. The overall success rate (8-11%) was significantly lower than the industry standard (17%). Overall survival (OS) as a secondary outcome appeared more predictive than primary endpoints that were surrogate, of overall success. Further, targeted therapies appear more successful in these lymphoma sub-types than broad acting drugs. Conclusion. Clinical trial risk in NHL, with an 89% failure rate reported here, may be reduced by basing decisions on OS secondary endpoints and biologic drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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