当前位置： SCI文献检索 > Therapeutic Innovation & Regulatory Science期刊下所有文献 > Methods for Employing Information About Uncertainty of Ascertainment of Events in Clinical Trials.

Methods for Employing Information About Uncertainty of Ascertainment of Events in Clinical Trials.

Abstract：

BACKGROUND:Uncertain ascertainment of events in clinical trials has been noted for decades. To correct possible bias, Clinical Endpoint Committees (CECs) have been employed as a critical element of trials to ensure consistent and high-quality endpoint evaluation, especially for cardiovascular endpoints. However, the efficiency and usefulness of adjudication have been debated. METHODS:The multiple imputation (MI) method was proposed to incorporate endpoint event uncertainty. In a simulation conducted to explain this methodology, the dichotomous outcome was imputed each time with subject-specific event probabilities. As the final step, the desired analysis was conducted based on all imputed data. This proposed method was further applied to real trial data from PARADIGM-HF. RESULTS:Compared with the conventional Cox model with adjudicated events only, the Cox MI method had higher power, even with a small number of uncertain events. It yielded more robust inferences regarding treatment effects and required a smaller sample size to achieve the same power. CONCLUSIONS:Instead of using dichotomous endpoint data, the MI method enables incorporation of event uncertainty and eliminates the need for categorizing endpoint events. In future trials, assigning a probability of event occurrence for each event may be preferable to a CEC assigning a dichotomous outcome. Considerable resources could be saved if endpoint events can be identified more simply and in a manner that maintains study power.

journal_name

Ther Innov Regul Sci

journal_title

Therapeutic innovation & regulatory science

authors

Chen Y,Lawrence J,Hung HMJ,Stockbridge N

doi

10.1007/s43441-020-00206-3

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

197-211

issue

1

eissn

2168-4790

issn

2168-4804

pii

10.1007/s43441-020-00206-3

journal_volume

55

pub_type

杂志文章

相关文献

Therapeutic Innovation & Regulatory Science文献大全
  • A Framework for Managing the Minimal Clinically Important Difference in Clinical Trials.

    abstract：:There is a long history of discussions about what is a minimal clinically important difference (MCID) and how this term applies to clinical research. This paper deals with a practical framework for MCID and its applicability to clinical trials. A literature review on the topic confirmed the fundamental role of MCID fo...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479013487541

    authors： Koynova D,Lühmann R,Fischer R

    更新日期：2013-07-01 00:00:00

  • Risk Evaluation and Mitigation Strategies With Elements to Assure Safe Use: Alignment of the Goals With the Tools to Manage Risk.

    abstract：:The Food and Drug Administration Amendments Act of 2007 gave the FDA the authority to require drug sponsors to submit a risk evaluation and mitigation strategies (REMS) program for those medicines with serious risks such that failure to effectively manage these risks would tip the benefit-risk balance. As of August 8,...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479014527749

    authors： Cronin M,Berger S,Seligman PJ

    更新日期：2014-11-01 00:00:00

  • An Analysis of Regulatory Timing and Outcomes for New Drug Applications Submitted to Swissmedic: Comparison With the US Food and Drug Administration and the European Medicines Agency.

    abstract：BACKGROUND:This study compared the timing, regulatory marketing authorization decisions, and the final labeling for products submitted to Swissmedic to those submitted to European Medicines Agency (EMA) and the US Food & Drug Administration (FDA). METHODS:The Centre for Innovation in Regulatory Science (CIRS) conducte...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479016655841

    authors： Dörr P,Wadworth A,Wang T,McAuslane N,Liberti L

    更新日期：2016-11-01 00:00:00

  • Evaluation of the Performance of the South Africa Regulatory Agency: Recommendations for Improved Patients' Access to Medicines.

    abstract：BACKGROUND:Timely access to new medicines may be addressed through strengthening of registration efficiencies and timelines by establishing and refining value-added registration processes, resources, and systems. The aims of this study were to evaluate the timelines of the milestones of the South African review process...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-019-00013-5

    authors： Keyter A,Salek S,Gouws J,Banoo S,Walker S

    更新日期：2020-07-01 00:00:00

  • ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder.

    abstract：:Attention deficit hyperactivity disorder (ADHD) is the most common neurobiological disorder in children, with a prevalence of ~6-7%1,2 that has remained stable for decades2. The social and economic burden associated with patients3, families, and broader systems (healthcare/educational) is substantial, with the annual ...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479015599811

    authors： Connolly JJ,Glessner JT,Elia J,Hakonarson H

    更新日期：2015-09-01 00:00:00

  • Regulatory Issues of Voluntary Certification of Food Supplements in Russia.

    abstract：:When registering food supplements in Russia, restrictions on the labeling and consumer leaflet contents are tightly controlled by the regulatory agencies. Thus, misleading advertising is the most difficult problem with the turnover of these products if information in the commercials does not correspond to the informat...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章,评审

    doi：10.1007/s43441-019-00043-z

    authors： Lozda R

    更新日期：2020-01-01 00:00:00

  • A Universal Framework for the Benefit-Risk Assessment of Medicines: Is This the Way Forward?

    abstract：:A universal framework for the evaluation of the benefit-risk assessment of medicines during development by pharmaceutical companies and in the regulatory review by regulatory authorities is considered of value, as it would result in the systematic structured approach to support transparency in decision making. Several...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479014547421

    authors： Walker S,McAuslane N,Liberti L,Leong J,Salek S

    更新日期：2015-01-01 00:00:00

  • Principled Structured Incorporation of Clinical Knowledge Into Strategic Development Decisions.

    abstract：:Efficient use of limited pharmaceutical product development resources requires integrating multiple attributes, such as efficacy, safety, pharmacology, and so on, to decide at any stage whether the development of a product should proceed aggressively or slowly or be terminated. The decision process proceeds most effec...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479014558273

    authors： Gould AL,Krishna R,Khan A,Saltzman J

    更新日期：2015-03-01 00:00:00

  • New Drug and Biologics Approvals in 2019: A Systematic Analysis of Patient Experience Data in FDA Drug Approval Packages and Product Labels.

    abstract：BACKGROUND:The FDA Patient-Focused Drug Development Initiative was launched to ensure the incorporation of the patient voice into drug development and evaluation. Since 2017, the FDA must publish a statement outlining patient experience data (PED) considered in the approval of new drugs. This study investigated the pre...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00244-x

    authors： Schultz-Knudsen K,Sabaliauskaite U,Hellsten J,Lassen AB,Morant AV

    更新日期：2020-11-23 00:00:00

  • Validation of QT Interval Correction Methods When a Drug Changes Heart Rate.

    abstract：:The QT interval is correlated with heart rate; therefore, the QT interval is usually corrected by heart rate when drug-induced QT effect is studied. Currently, there are many correction methods that use either fixed or data-driven approaches. The effectiveness of correction methods depends on many factors and varies f...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479012467018

    authors： Dang Q,Zhang J

    更新日期：2013-03-01 00:00:00

  • Labeling Standards for Biosimilar Products.

    abstract：:In 2010 Congress established a regulatory pathway for the approval of biosimilar products in the United States. FDA has embarked on developing the implementation framework for this pathway which includes creating guidance to assist biosimilar manufacturers in the development of these products. However, to date, the gu...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479013515249

    authors： Davis GC,Bowker GM

    更新日期：2014-05-01 00:00:00

  • Over-the-Counter Drugs: Regulatory Analysis of Warning Letters Between Fiscal Years 2015-2019.

    abstract：BACKGROUND:According to 21 Code of Federal Regulation (CFR) Part 211, Over-the-Counter (OTC) drug manufacturers must establish and follow current good manufacturing practices (cGMP) to produce quality products while meeting regulatory standards. The warning letters issued by the U.S. Food and Drug Administration (FDA) ...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00231-2

    authors： Bai HK,Ahearn JD,Bartlett MG

    更新日期：2020-10-23 00:00:00

  • Medicines Adaptive Pathways to Patients (MAPPs): A Story of International Collaboration Leading to Implementation.

    abstract：:After nearly a decade of discussion, analysis, and development, the Medicines Adaptive Pathways to Patients (MAPPs) initiative is beginning to see acceptance from regulators, industry, patients, and payers, with the first live pilot project initiated under the guidance of the European Medicines Agency in 2014. Althoug...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479015618697

    authors： Schulthess D,Baird LG,Trusheim M,Unger TF,Lumpkin M,Hoos A,Garner S,Gavin P,Goldman M,Seigneuret N,Chlebus M,Van Baelen K,Bergstrom R,Hirsch G

    更新日期：2016-05-01 00:00:00

  • Single-Study Approvals: Quantum of Evidence Required.

    abstract：:When does a single positive adequate and well-controlled study of a new drug meet the statutory requirement to demonstrate substantial evidence of effectiveness? The answer to this question, particularly with respect to new molecular entities, has been of considerable debate since 1962 when the requirement that new dr...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-019-00103-4

    authors： Sasinowski FJ,Butler ML

    更新日期：2020-05-01 00:00:00

  • Alternative New Mono-scaled Quantitative Benefit-Risk Assessment of Human Papillomavirus Vaccine in Japan.

    abstract：BACKGROUND:The human papillomavirus (HPV) vaccine coverage is very low in Japan since the government suspended the active encouragement of the vaccination. We aimed to conduct a benefit-risk assessment of HPV vaccination and explore different consequent scenarios to identify potential improvements to the current Japane...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00189-1

    authors： Matsumoto T,Matsumaru N,Scuffham P,Neels P,Tsukamoto K

    更新日期：2021-01-01 00:00:00

  • Lessons Learned From Hundreds of Thorough QT Studies.

    abstract：BACKGROUND:The coherence between the relationship of QTc and drug plasma concentration (this relationship is measured through the slope) and ICH E14 findings based on hundreds of QT study reports was studied. RESULTS:Based on ICH E14 analysis, our findings indicate that if the slope was not positive, in most cases (86...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479014563549

    authors： Zhang J,Chen H,Tsong Y,Stockbridge N

    更新日期：2015-05-01 00:00:00

  • Analyzing Upward Deviation of Actual vs Predicted Drug Sales in Japan for a Reasonable Drug-Pricing Policy.

    abstract：BACKGROUND:Predictions of drug sales play an important role in setting drug prices in Japan, where drug prices are highly regulated. One of 2 primary Japanese drug-pricing methodologies-the cost calculation method- refers extensively to the prediction of drug sales in establishing drug prices. Deviations from predicted...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479019860123

    authors： Shibata S,Fukumoto D,Suzuki T,Ozaki K

    更新日期：2019-07-16 00:00:00

  • Differences in Clinical Research Perceptions and Experiences by Age Subgroup.

    abstract：BACKGROUND:(1) To assess the differing viewpoints of actual and potential adult clinical trial participants in 5 age cohorts, (2) identify misperceptions and opportunities to reduce unnecessary burdens on volunteers, and (3) provide age-specific feedback to study sponsors on their current engagement efforts. METHODS:B...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-019-00033-1

    authors： Anderson A,Borfitz D,Getz K

    更新日期：2020-01-01 00:00:00

  • Comparative Assessment of Non-trial Access to Investigational Medical Products in the U.S. and Japan.

    abstract：:The U.S. and Japan have preapproval access systems for patients who have exhausted approved treatment options. We compare the systems of both countries and discuss some ethical concerns surrounding non-trial access to investigational drugs. Notable points of comparison of the two countries' systems include cost of non...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00228-x

    authors： Nakada H,Folkers KM,Takashima K

    更新日期：2020-10-23 00:00:00

  • Implementing the Principle of the 3 Rs Through the Indian Pharmacopoeia.

    abstract：:Quality and safety tests are required for regulatory approval of drugs and pharmaceuticals in the country to guarantee minimum safety standards, and most of these tests include animal usage. In the case of biological medicines, these safety and quality tests have to be performed on a batch-to-batch basis and require a...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479015572371

    authors： Rastogi S,Kalaivani M,Bhatia AK,Prakash J,Singh GN

    更新日期：2015-09-01 00:00:00

  • Risk-Based Monitoring (RBM) Implementation: Challenges and Potential Solutions.

    abstract：:Risk-based monitoring (RBM) has disrupted the clinical trial industry, challenging conventional monitoring norms, business processes, and organizational structures. Endorsed by regulators and leading industry forums, and further driven by escalating drug development costs and enabling technology shifts making data ava...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479018769284

    authors： Limaye N,Jaguste V

    更新日期：2019-03-01 00:00:00

  • Factors that have an Impact on Abbreviated New Drug Application (ANDA) Submissions.

    abstract：BACKGROUND:Increasing generic drug price competition by facilitating abbreviated new drug applications (ANDA) submission may help patients have access to affordable care. This study examined factors associated with first ANDA submission for the brand drug to be copied [the "reference listed drug" (RLD)]. METHODS:This ...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00163-x

    authors： Wittayanukorn S,Rosenberg M,Schick A,Hu M,Wang Z,Babiskin A,Lionberger R,Zhao L

    更新日期：2020-11-01 00:00:00

  • A Practical Estimation Method for Analyzing Adverse Drug Reactions Using Data Mining.

    abstract：:This study aimed to determine the potentially severe chemical properties of drugs that can cause adverse drug reactions (ADRs) such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) by using a data mining method. The study data were extracted from the Adverse Event Repor...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/0092861512460759

    authors： Shirakuni Y,Okamoto K,Uejima E,Inui S,Takahara JI,Ohgaru T,Yamasaki H,Tian Y,Kawashita N,Inoue R,Yasunaga T,Takagi T

    更新日期：2013-03-01 00:00:00

  • How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement.

    abstract：BACKGROUND:Pediatric regulations enacted in both Europe and the USA have disrupted the pharmaceutical industry, challenging business and drug development processes, and organizational structures. Over the last decade, with science and innovation evolving, industry has moved from a reactive to a proactive mode, investin...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00116-4

    authors： Severin T,Corriol-Rohou S,Bucci-Rechtweg C,An Haack K,Fuerst-Recktenwald S,Lepola P,Norjavaara E,Dehlinger-Kremer M,EFGCP Children’s Medicines Working Party.,Haertter S,Cheung SYA,IQ Pediatric Working Group.

    更新日期：2020-09-01 00:00:00

  • How FDA Advisory Committee Members Prepare and What Influences Them.

    abstract：:Since 1992 many changes have occurred in the regulations, guidelines, and processes governing the FDA, the biomedical industry, other stakeholders, and their interactions. Of particular importance, the FDA Amendments Act of 2007 made public advisory committee meetings mandatory for new molecular entities and devices r...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/0092861512458096

    authors： McIntyre TD,Pappas M,DiBiasi JJ

    更新日期：2013-01-01 00:00:00

  • Interdisciplinary Safety Evaluation and Quantitative Safety Monitoring: Introduction to a Series of Papers.

    abstract：:The American Statistical Association and DIA have created an interdisciplinary working group of drug safety experts from academia, industry and regulatory backgrounds to explore the future direction for safety monitoring. This introduction to the series explains the background and rationale for this special section. ...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479018793130

    authors： Seltzer JH,Li J,Wang W

    更新日期：2019-03-29 00:00:00

  • Characteristics of Drug Intervention Clinical Trials and Scientific Impact of the Trial Outcome: A Bibliometric Analysis Using the Relative Citation Ratio in Non-small Cell Lung Cancer from 2007 to 2016.

    abstract：BACKGROUND:Although a large number of clinical trials have been conducted, the types of clinical trials that are scientifically influential, frequently utilized by society, and contribute to the progress of evidence-based medicine (EBM) have not been studied. Thus, we aimed to investigate the relationship between the c...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00177-5

    authors： Noguchi Y,Kaneko M,Narukawa M

    更新日期：2020-11-01 00:00:00

  • Sentiment of Media Coverage and Reputation of the Pharmaceutical Industry.

    abstract：BACKGROUND:Patients and health care professionals receive information about pharmaceutical companies through various sources, including but not limited to print media, social media, and electronic media. The objective of this research was to benchmark the sentiment of electronic newspaper media coverage between 2014 an...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-019-00048-8

    authors： Pampulevski V,Giaquinto JR,Rametta M,Toscani M,Barone J,Nadal JC

    更新日期：2020-01-01 00:00:00

  • Communicating Immunogenicity-Associated Risk in Current U.S. FDA Prescription Drug Labeling: A Systematic Evaluation.

    abstract：BACKGROUND:Communicating the clinical impact of immunogenicity in labeling is important for safe and effective use of certain prescription products. Current U.S. Food and Drug Administration (FDA) guidance does not provide comprehensive recommendations on the communication of clinical impact of immunogenicity in labeli...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1007/s43441-020-00161-z

    authors： Guinn D,Madabushi R,Wang YM,Brodsky E,Zineh I,Maxfield K

    更新日期：2020-11-01 00:00:00

  • Regulatory Definitions and Good Pharmacovigilance Practices in Social Media: Challenges and Recommendations.

    abstract：:Social media presents new challenges to the biopharmaceutical industry for conducting pharmacovigilance activities. The authors reviewed worldwide regulatory guidance documents related to monitoring of adverse events posted on social media sites and identified gaps in current regulatory definitions for pharmacovigilan...

    journal_title：Therapeutic innovation & regulatory science

    pub_type： 杂志文章

    doi：10.1177/2168479015587362

    authors： Naik P,Umrath T,van Stekelenborg J,Ruben R,Abdul-Karim N,Boland R,Ibara M,Ekuta J,Washburn D,Stergiopoulos S

    更新日期：2015-11-01 00:00:00