Scholars@Duke
Frank Wesley Rockhold

Frank Wesley Rockhold

Professor of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Biostatistics
frank.rockhold@duke.edu
Duke Box 3850, Durham, NC 27710
200 Morris Street, 6428 200 Morris, Durham, NC 27701

Scholarly Works - Journal articles

Methodologic Standards for Follow-Up Extension in Cardiovascular Trials: A Scientific Statement From the American Heart Association

Journal article Circulation · August 3, 2026 Extension follow-up trials are essential for understanding the long-term safety and efficacy of cardiovascular interventions. Whereas primary randomized trials primarily capture short ... Full text Cite

Long-term safety of the Pfizer-BioNTech COVID-19 vaccine: Results from the HERO-together study.

Journal article Respir Med · June 2026 BACKGROUND: COVID-19 vaccines were initially authorized based on short-term data from Phase 3 clinical trials in a highly selected population. OBJECTIVES: This study assessed the long-term safety of the Pfizer-BioNTech COVID-19 vaccine BNT162b2 and variati ... Full text Link to item Cite

Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial.

Journal article Eur Heart J Cardiovasc Imaging · April 30, 2026 AIMS: To assess whether baseline functional performance assessed by exercise treadmill stress testing (EST) has additive value to coronary computed tomography angiography (CCTA) for risk stratification among patients with chronic coronary disease (CCD) and ... Full text Link to item Cite

Extension Reports in Clinical Trials: A Systematic Review and Consequent Guidance.

Journal article J Am Coll Cardiol · April 21, 2026 BACKGROUND: Following the primary publication of a clinical trial, questions of longer-term efficacy and safety remain unanswered. Investigators often have sequel publications based on extended follow-up; yet, no guidelines exist for such extension reports ... Full text Link to item Cite

Apolipoprotein E Mimetic Peptide CN-105 and Postoperative Delirium in Older Patients: The Phase 2 MARBLE Randomized Clinical Trial.

Journal article JAMA Netw Open · April 1, 2026 IMPORTANCE: The apolipoprotein E (APOE) gene ε4 allele leads to increased Alzheimer disease risk and neuroinflammation and is also believed to play a role in postoperative delirium. However, the safety and feasibility of modulating apoE protein signaling t ... Full text Link to item Cite

Determinants of publication likelihood and timeliness for clinical studies.

Journal article J Clin Transl Sci · 2026 INTRODUCTION: Timely dissemination of clinical trial results is essential to advance knowledge, guide practice, and improve outcomes, yet many trials remain unpublished, limiting impact. We examine what drives publication and timelines across three major c ... Full text Link to item Cite

Prediction and Longer-Term Outcomes of All-cause and Cardiovascular Mortality in the HEART-FID Trial.

Journal article J Card Fail · December 2025 BACKGROUND: The HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose [FCM] as Treatment for Heart Failure with Iron Deficiency) is the largest trial to test intravenous iron (ferric carboxymaltose [FCM]) vs placebo in patients with ... Full text Link to item Cite

Functional and Prognostic Implications of Different Iron Deficiency Definitions in Heart Failure: Insights From HEART-FID.

Journal article JACC Heart Fail · December 2025 BACKGROUND: Iron deficiency (ID) is common in patients with heart failure (HF), but optimal use of circulating iron indices as diagnostic criteria and for defining treatment targets remain uncertain. OBJECTIVES: This study sought how to determine how indiv ... Full text Link to item Cite

Distal Radius Interventions for Fracture Treatment (DRIFT) trial: study protocol for a multicentre randomised clinical trial of completely translated distal radius fractures at paediatric hospitals in North America.

Journal article BMJ Open · October 29, 2025 INTRODUCTION: Distal radius fractures are the most common fractures seen in the emergency department in children in the USA. However, no established or standardised guidelines exist for the optimal management of completely displaced fractures in younger ch ... Full text Open Access Link to item Cite

Decentralized Clinical Trials in the Era of Real-World Evidence: A Critical Assessment of Recent Experiences.

Journal article Clin Transl Sci · September 2025 Since the first decentralized clinical trial (DCT) was conducted in 2011, there has been an increased usage of DCT due to its benefits of patient-centricity and generalizability of findings. This trend was further expedited by the global COVID-19 pandemic. ... Full text Link to item Cite

SPIRIT 2025 Statement: Updated Guideline for Protocols of Randomized Trials.

Journal article JAMA · August 5, 2025 IMPORTANCE: The protocol of a randomized trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Stand ... Full text Link to item Cite

Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency.

Journal article Nat Med · August 2025 Uncertainty remains about the effect of intravenous (i.v.) iron on outcomes for heart failure (HF) with iron deficiency. In the present study, we summarize the efficacy and safety of i.v. iron from six trials (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEAR ... Full text Link to item Cite

Family caregiver observations of pain behaviors in infants and young children less than 3 years of age.

Journal article J Pain · August 2025 Pain in very young, preverbal children is often inadequately assessed and thus poorly treated, leading to short- and long-term negative consequences. Family caregivers are often the primary observers of young children's pain, but their perspectives are oft ... Full text Link to item Cite

CONSORT 2025 Statement: Updated Guideline for Reporting Randomized Trials.

Journal article JAMA · June 10, 2025 IMPORTANCE: Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of health care interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Con ... Full text Link to item Cite

Asundexian or Apixaban in Patients With Atrial Fibrillation According to Prior Oral Anticoagulant Use: A Subgroup Analysis of the OCEANIC-AF Randomized Clinical Trial.

Journal article JAMA Cardiol · June 1, 2025 IMPORTANCE: In patients with atrial fibrillation (AF), oral anticoagulants (OACs) reduce the risk of stroke. OBJECTIVE: To investigate if patients with less prior OAC exposure respond differently to a new OAC than patients with more OAC exposure. DESIGN, S ... Full text Link to item Cite

CONSORT 2025 statement: updated guideline for reporting randomized trials.

Journal article Nat Med · June 2025 Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Sta ... Full text Link to item Cite

SPIRIT 2025 statement: updated guideline for protocols of randomized trials.

Journal article Nat Med · June 2025 The protocol of a randomized trial is the foundation for study planning, conduct, reporting and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol ... Full text Link to item Cite

SPIRIT 2025 statement: updated guideline for protocols of randomised trials.

Journal article Lancet · May 17, 2025 The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol ... Full text Link to item Cite

Characterization of serum phosphate levels over time with intravenous ferric carboxymaltose versus placebo as treatment for heart failure with reduced ejection fraction and iron deficiency: An exploratory prospective substudy from HEART-FID.

Journal article Eur J Heart Fail · May 2025 AIMS: Ferric carboxymaltose (FCM) is guideline-recommended for iron deficiency (ID) in heart failure with reduced ejection fraction (HFrEF). Despite a well-established safety profile, the magnitude and clinical significance of FCM-induced hypophosphataemia ... Full text Link to item Cite

Sample Size and Power Calculations With Win Measures Based on Hierarchical Endpoints.

Journal article Stat Med · May 2025 Win measures, such as win ratio, win odds, net benefit, and desirability of outcome ranking (DOOR), have become popular approaches for the analysis of hierarchical endpoints in clinical studies. Sample size and power calculations with win measures based on ... Full text Link to item Cite

SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials.

Journal article BMJ · April 28, 2025 High quality protocols facilitate proper planning, conduct, reporting, and external review of randomised trials, yet their completeness varies and key elements are often not considered. To strengthen good reporting of trial protocols, the SPIRIT (Standard ... Full text Link to item Cite

SPIRIT 2025 statement: updated guideline for protocols of randomised trials.

Journal article BMJ · April 28, 2025 IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Stand ... Full text Link to item Cite

CONSORT 2025 statement: updated guideline for reporting randomised trials.

Journal article Lancet · April 14, 2025 Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Sta ... Full text Link to item Cite

CONSORT 2025 statement: updated guideline for reporting randomised trials.

Journal article BMJ · April 14, 2025 BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Cons ... Full text Link to item Cite

CONSORT 2025 explanation and elaboration: updated guideline for reporting randomised trials.

Journal article BMJ · April 14, 2025 Critical appraisal of the quality of randomised trials is possible only if their design, conduct, analysis, and results are completely and accurately reported. Without transparent reporting of the methods and results, readers will not be able to fully eval ... Full text Link to item Cite

Guideline-Directed Medical Therapy and Outcomes in the ISCHEMIA Trial.

Journal article J Am Coll Cardiol · April 1, 2025 BACKGROUND: Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their atta ... Full text Link to item Cite

CONSORT 2025 statement: Updated guideline for reporting randomised trials.

Journal article PLoS Med · April 2025 BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Cons ... Full text Link to item Cite

SPIRIT 2025 statement: Updated guideline for protocols of randomised trials.

Journal article PLoS Med · April 2025 IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Stand ... Full text Link to item Cite

Decentralized Clinical Trials in the Era of Real-World Evidence: A Statistical Perspective.

Journal article Clin Transl Sci · February 2025 There has been a growing trend that activities relating to clinical trials take place at locations other than traditional trial sites (hence decentralized clinical trials or DCTs), some of which are at settings of real-world clinical practice. Although the ... Full text Link to item Cite

Asundexian versus Apixaban in Patients with Atrial Fibrillation.

Journal article N Engl J Med · January 2, 2025 BACKGROUND: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent s ... Full text Link to item Cite

Trial Design with Win Statistics for Multiple Time-to-Event Endpoints with Hierarchy

Journal article Statistics in Biopharmaceutical Research · January 1, 2025 The conventional approach to the analysis of composite endpoints is time-to-first event analysis. However, this approach has been criticized because it ignores the differences in clinical severity and may end up emphasizing the less severe time-to-event. T ... Full text Cite

CONSORT 2025 Statement:updated guideline for reporting randomized trials

Journal article Japanese Pharmacology and Therapeutics · January 1, 2025 Background Well-designed and well-conducted randomized controlled trials (RCTs) are considered the most reliable evidence regarding the benefits of healthcare interventions. However, there is overwhelming evidence that reporting quality is suboptimal. CONS ... Cite

SPIRIT 2025 Statement: updated guideline for protocols of randomised trials

Journal article Japanese Pharmacology and Therapeutics · January 1, 2025 IMPORTANCE Randomized controlled trial protocols form the basis for study planning, conduct, reporting, and external review (peer review). However, the completeness of trial protocols varies, and important elements of trial design and conduct are often not ... Cite

Clinical Study Report and Individual Participant Data Transparency for US Food and Drug Administration-Approved Anticancer Drugs: A Call for Systematic Data Availability.

Journal article J Clin Oncol · November 10, 2024 Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance ... Full text Link to item Cite

Framework of the strengths and challenges of clinically integrated trials: An expert panel report.

Journal article Am Heart J · September 2024 The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generati ... Full text Link to item Cite

The Case for Access to Data Monitoring Committee Charters.

Journal article NEJM Evid · September 2024 AbstractClinical trials investigating novel or high-risk interventions often use data monitoring committees (DMCs) to ensure that the participants' best interests are safeguarded. The typical DMC charter describes procedures by which the DMC operates, incl ... Full text Link to item Cite

Training the Next Generation of Data Monitoring Committee Members: An Initiative of the Heart Failure Collaboratory.

Journal article JACC Heart Fail · August 2024 Clinical trials are vital for assessing therapeutic interventions. The associated data monitoring committees (DMCs) safeguard patient interests and enhance trial integrity, thus promoting timely, reliable evaluations of those interventions. We face an urge ... Full text Link to item Cite

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

Journal article Circ Cardiovasc Interv · June 2024 BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coron ... Full text Link to item Cite

Training New DMC Members: A Call to Action.

Journal article Ther Innov Regul Sci · March 2024 Historically, clinical trialists developed DMC expertise and experience with "on the job training". Clinical trialists have recognized a large and growing gap between the demand and supply of trained DMC members due in part to the huge increase in ongoing ... Full text Link to item Cite

Accessibility of clinical study reports supporting medicine approvals: a cross-sectional evaluation.

Journal article J Clin Epidemiol · March 2024 OBJECTIVES: Clinical study reports (CSRs) are highly detailed documents that play a pivotal role in medicine approval processes. Though not historically publicly available, in recent years, major entities including the European Medicines Agency (EMA), Heal ... Full text Link to item Cite

Hierarchical End Points in Prior Heart Failure Trials and the HEART-FID Trial.

Journal article Circ Heart Fail · February 2024 BACKGROUND: Clinical trials in heart failure (HF) traditionally use time-to-event analyses focusing on death and hospitalization for HF. These time-to-first event analyses may have more limited abilities to assess the probability of benefiting from a thera ... Full text Link to item Cite

Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.

Journal article N Engl J Med · January 11, 2024 BACKGROUND: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more ... Full text Link to item Cite

Baseline characteristics of patients in the randomized study to investigate the efficacy and safety of ferric carboxymaltose as treatment for heart failure with iron deficiency: HEART-FID trial.

Journal article Am Heart J · December 2023 BACKGROUND: Prior clinical trials have investigated intravenous iron in patients with heart failure (HF) and iron deficiency, but the safety and efficacy of this therapy remains unclear. METHODS: We report the baseline demographics and clinical characteris ... Full text Link to item Cite

Heterogeneity and Utility of Pharmaceutical Company Sharing of Individual-Participant Data Packages.

Journal article JAMA Oncol · December 1, 2023 IMPORTANCE: The pharmaceutical industry has made substantial investments in developing processes for sharing individual-participant data (IPD) from clinical trials. However, the utility and completeness of shared IPD and supporting documents must be evalua ... Full text Link to item Cite

Impact of Complete Revascularization in the ISCHEMIA Trial.

Journal article J Am Coll Cardiol · September 19, 2023 BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients un ... Full text Link to item Cite

Ferric Carboxymaltose in Heart Failure with Iron Deficiency.

Journal article N Engl J Med · September 14, 2023 BACKGROUND: Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical even ... Full text Link to item Cite

Bringing data monitoring committee charters into the sunlight.

Journal article Clin Trials · August 2023 Clinical trials investigating novel or high risk interventions, or studying vulnerable participants, often use a data monitoring committee to oversee the progress of the trial. The data monitoring committee serves both an ethical and a scientific function, ... Full text Link to item Cite

The Data Monitoring Committee: A Collective or a Collection?

Journal article Ther Innov Regul Sci · July 2023 In this commentary, we urge that a Data Monitoring Committee (DMC) should operate as a collective, that is, as a unitary whole. In so doing, its recommendations should emerge through a consensus development process, not through a vote of the members. The s ... Full text Link to item Cite

Institutional approaches to preventing questionable research practices.

Journal article Account Res · May 2023 Questionable research practices (QRP) are actions taken by researchers that span a range of concern related to violation of research best practices, and ultimately expose institutions and research participants to risk. Numerous studies have shown that QRP ... Full text Link to item Cite

Impact of Vaccination With the SCB-2019 Coronavirus Disease 2019 Vaccine on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Household Contact Study in the Philippines.

Journal article Clin Infect Dis · April 3, 2023 BACKGROUND: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between household ... Full text Link to item Cite

Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

Journal article JACC Cardiovasc Interv · January 23, 2023 BACKGROUND: In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively). OBJECTIVES: This prespecifi ... Full text Link to item Cite

The Current Landscape in Biostatistics of Real-World Data and Evidence: Clinical Study Design and Analysis

Journal article Statistics in Biopharmaceutical Research · January 1, 2023 Real-world data (RWD), such as electronic health records, reimbursement requests as adjudicated by health insurance companies, and health survey data as collected by government agencies or other research organizations, are increasingly used in drug develop ... Full text Cite

The Current Landscape in Biostatistics of Real-World Data and Evidence: Causal Inference Frameworks for Study Design and Analysis

Journal article Statistics in Biopharmaceutical Research · January 1, 2023 As real-world data (RWD) become more readily available, the regulatory agencies, medical product developers, and other key stakeholders have increasing interests in exploring the use of real-world evidence (RWE) to support regulatory decisions alternative ... Full text Cite

Biostatistical Considerations When Using RWD and RWE in Clinical Studies for Regulatory Purposes: A Landscape Assessment

Journal article Statistics in Biopharmaceutical Research · January 1, 2023 Real-world evidence (RWE), derived from data from “real-world” clinical practice and medical product utilization, is an increasingly important source of evidence that holds great potential to increase efficiency and improve clinical development and life cy ... Full text Cite

Statistical Consideration for Fit-for-Use Real-World Data to Support Regulatory Decision Making in Drug Development

Journal article Statistics in Biopharmaceutical Research · January 1, 2023 A Real-World Evidence (RWE) scientific working group of the American Statistical Association Biopharmaceutical Section has been reviewing the statistical considerations for the generation of real-world evidence to support regulatory decision making. As par ... Full text Cite

Real-world evidence for regulatory decision-making: updated guidance from around the world.

Journal article Front Med (Lausanne) · 2023 Leveraging the value of real-world evidence (RWE) to make informed regulatory decisions in the field of health care continues to gain momentum. Improving clinical evidence generation by evaluating the outcomes and patient experiences at the point-of-care w ... Full text Link to item Cite

Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

Journal article Circ Cardiovasc Qual Outcomes · October 2022 BACKGROUND: Patients with chronic kidney disease (CKD) on dialysis (CKD G5D) have worse cardiovascular outcomes than patients with advanced nondialysis CKD (CKD G4-5: estimated glomerular filtration rate <30 mL/[min·1.73m2]). Our objective was to evaluate ... Full text Link to item Cite

The Impact of Landscape Changes on Data and Safety Monitoring Board Oversight of Clinical Trials.

Journal article NEJM Evid · September 2022 Impact of Landscape Changes on DSMB OversightThis Clinical Trials Workshop describes how external factors (or landscape changes) can affect monitoring of an ongoing clinical trial and discusses issues to consider to avoid stopping a trial too early while m ... Full text Open Access Link to item Cite

Cardiovascular and Renal Implications of Myocardial Infarction in the ISCHEMIA-CKD Trial.

Journal article Circ Cardiovasc Interv · August 2022 BACKGROUND: ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) reported an initial invasive treatment strategy did not reduce the risk of death or nonfatal myocardial infarctio ... Full text Link to item Cite

Exploratory analyses of clinical trial data used for health technology assessments: a retrospective evaluation.

Journal article BMJ Open · July 29, 2022 OBJECTIVES: To examine the validity and statistical limitations of exploratory analyses of clinical trial data commonly requested by agencies responsible for determining which medical products may be financed or reimbursed by a healthcare system. DESIGN: T ... Full text Link to item Cite

Impact of previous exposure to SARS-CoV-2 and of S-Trimer (SCB-2019) COVID-19 vaccination on the risk of reinfection: a randomised, double-blinded, placebo-controlled, phase 2 and 3 trial.

Journal article Lancet Infect Dis · July 2022 BACKGROUND: We previously reported the efficacy of the adjuvanted-protein COVID-19 vaccine candidate S-Trimer (SCB-2019) in adults who showed no evidence of previous exposure to SARS-CoV-2. In this study, we aimed to investigate the extent of protection af ... Full text Link to item Cite

Approach for reporting master protocol study designs on ClinicalTrials.gov: qualitative analysis.

Journal article BMJ · June 10, 2022 OBJECTIVE: To describe an approach for reporting master protocol research programs (MPRPs) that is consistent with existing good reporting practices and that uses structured information to convey the overall master protocol and design of each substudy. DES ... Full text Link to item Cite

Total Cardiovascular and Limb Events and the Impact of Polyvascular Disease in Chronic Symptomatic Peripheral Artery Disease.

Journal article J Am Heart Assoc · June 7, 2022 Background Peripheral artery disease (PAD) is associated with heightened risk for major adverse cardiovascular and limb events, but data on the burden of risk for total (first and potentially subsequent) events, and the association with polyvascular diseas ... Full text Link to item Cite

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

Journal article N Engl J Med · April 21, 2022 BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In t ... Full text Link to item Cite

Clinical events classification (CEC) in clinical trials: Report on the current landscape and future directions - proceedings from the CEC Summit 2018.

Journal article Am Heart J · April 2022 IMPORTANCE: Clinical events adjudication is pivotal for generating consistent and comparable evidence in clinical trials. The methodology of event adjudication is evolving, but research is needed to develop best practices and spur innovation. OBSERVATIONS: ... Full text Link to item Cite

COVID-19 interventional trials: Analysis of data sharing intentions during a time of pandemic.

Journal article Contemp Clin Trials · April 2022 BACKGROUND: This survey of COVID-19 interventional studies encompasses, and expands upon, a previous publication [1] examining individual participant level data (IPD) sharing intentions for COVID-related trials and publications prior to June 30, 2020. METH ... Full text Link to item Cite

The challenges of data safety monitoring for a pragmatic study: Lessons from the ADAPTABLE study.

Journal article Contemp Clin Trials · April 2022 Data monitoring committees (DMCs) play a critical role in protecting the safety of participants and integrity of clinical studies. While there are well-established DMC guidelines for traditional, randomized controlled trials, the clinical trial community i ... Full text Link to item Cite

COVID-19 Trials: Who Participates and Who Benefits?

Journal article South Med J · April 2022 OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortalit ... Full text Open Access Link to item Cite

Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD.

Journal article J Am Heart Assoc · March 15, 2022 Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (Internat ... Full text Link to item Cite

Real-World Evidence for Regulatory Decision-Making: Guidance From Around the World.

Journal article Clin Ther · March 2022 PURPOSE: Interest in leveraging real-world evidence (RWE) to support regulatory decision making for product effectiveness has been increasing globally as evident by the increasing number of regulatory frameworks and guidance documents. However, acceptance ... Full text Link to item Cite

World regional differences in outcomes for patients with peripheral artery disease: Insights from the EUCLID trial.

Journal article Vasc Med · February 2022 Regional variations exist in the epidemiology of peripheral artery disease (PAD), in comorbidities, use of secondary prevention, and outcomes. Large studies of these variations in worldwide populations are rare. The EUCLID (Examining Use of tiCagreLor In p ... Full text Open Access Link to item Cite

Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.

Journal article Lancet · January 29, 2022 BACKGROUND: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS: This ongoing phase 2 and 3 double-blind, placebo-contro ... Full text Link to item Cite

Use of Clinical Data Interchange Standards Consortium (CDISC) Standards for Real-world Data: Expert Perspectives From a Qualitative Delphi Survey.

Journal article JMIR Med Inform · January 27, 2022 BACKGROUND: Real-world data (RWD) and real-world evidence (RWE) are playing increasingly important roles in clinical research and health care decision-making. To leverage RWD and generate reliable RWE, data should be well defined and structured in a way th ... Full text Link to item Cite

Understanding Study Drug Discontinuation Through EUCLID.

Journal article Front Cardiovasc Med · 2022 INTRODUCTION: Disparities in the care and outcomes of peripheral artery disease (PAD) have been well-established. In part this is due to disparities in enrollment of PAD trial cohorts. However, less attention has been paid to non-random protocol non-adhere ... Full text Link to item Cite

Impact of chronic kidney disease on hemoglobin among patients with peripheral artery disease treated with P2Y12 inhibitors: Insights from the EUCLID trial.

Journal article Vasc Med · December 2021 Patients with chronic kidney disease may develop new or more severe anemia when treated with antiplatelet agents due to blood loss in conjunction with impaired erythropoiesis. Because anemia independently predicts limb amputation and mortality among patien ... Full text Link to item Cite

Primary and Secondary Outcome Reporting in Randomized Trials: JACC State-of-the-Art Review.

Journal article J Am Coll Cardiol · August 24, 2021 Consensus as to best practices for the selection, reporting, and interpretation of primary and secondary outcomes of randomized controlled trials is lacking. We reviewed the strategies adopted in publications of randomized controlled trials (RCTs) for the ... Full text Link to item Cite

Effect of COVID-19 on asthma exacerbation.

Journal article J Allergy Clin Immunol Pract · July 2021 Full text Link to item Cite

What can heart failure trialists learn from oncology trialists?

Journal article Eur Heart J · June 21, 2021 Globally, there has been little change in mortality rates from cardiovascular (CV) diseases or cancers over the past two decades (1997-2018). This is especially true for heart failure (HF) where 5-year mortality rates remain as high as 45-55%. In the same ... Full text Link to item Cite

Association of Heart Failure With Outcomes Among Patients With Peripheral Artery Disease: Insights From EUCLID.

Journal article J Am Heart Assoc · June 15, 2021 Background Peripheral artery disease (PAD) and heart failure (HF) are each independently associated with poor outcomes. Risk factors associated with new-onset HF in patients with primary PAD are unknown. Furthermore, how the presence of HF is associated wi ... Full text Link to item Cite

Randomized Placebo-Controlled Trial of Ferric Carboxymaltose in Heart Failure With Iron Deficiency: Rationale and Design.

Journal article Circ Heart Fail · May 2021 BACKGROUND: Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous ferric carboxymaltose leads to early a ... Full text Link to item Cite

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Journal article Nat Commun · April 15, 2021 Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine a ... Full text Open Access Link to item Cite

Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons.

Journal article Circulation · February 23, 2021 BACKGROUND: In the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality in comparison ... Full text Link to item Cite

A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial.

Journal article Contemp Clin Trials · February 2021 Asthma prevalence, morbidity, and mortality disproportionately impact African American/Black (AA/B) and Hispanic/Latinx (H/L) communities. Adherence to daily inhaled corticosteroid (ICS), recommended by asthma guidelines in all but the mildest cases of ast ... Full text Link to item Cite

Association of Chronic Obstructive Pulmonary Disease with Morbidity and Mortality in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial.

Journal article Int J Chron Obstruct Pulmon Dis · 2021 BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients ... Full text Link to item Cite

Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system.

Journal article Spinal Cord · December 2020 STUDY DESIGN: Narrative review. PURPOSE: To provide an overview of adaptive trial designs, and describe how adaptive methods can address persistent challenges encountered by randomized controlled trials of people with spinal cord injury (SCI). RESULTS: Wit ... Full text Link to item Cite

Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial.

Journal article Circulation · November 3, 2020 BACKGROUND: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction ... Full text Link to item Cite

Designing, Conducting, Monitoring, and Analyzing Data from Pragmatic Randomized Clinical Trials: Proceedings from a Multi-stakeholder Think Tank Meeting.

Journal article Ther Innov Regul Sci · November 2020 In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality ... Full text Link to item Cite

Cause of Death Among Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Journal article Circ Cardiovasc Qual Outcomes · November 2020 BACKGROUND: Peripheral artery disease is common and associated with high mortality. There are limited data detailing causes of death among patients with peripheral artery disease. METHODS: EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) w ... Full text Link to item Cite

Association of Health Status Scores With Cardiovascular and Limb Outcomes in Patients With Symptomatic Peripheral Artery Disease: Insights From the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) Trial.

Journal article J Am Heart Assoc · October 20, 2020 Background There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Result ... Full text Link to item Cite

Association of Disease Progression With Cardiovascular and Limb Outcomes in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Journal article Circ Cardiovasc Interv · October 2020 BACKGROUND: Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association ... Full text Link to item Cite

Association of Hypertension and Arterial Blood Pressure on Limb and Cardiovascular Outcomes in Symptomatic Peripheral Artery Disease: The EUCLID Trial.

Journal article Circ Cardiovasc Qual Outcomes · September 2020 BACKGROUND: Current guidelines recommend aggressive management of hypertension. Recent evidence suggested potential harm with low blood pressure targets in patients with peripheral artery disease. We investigated the association of a history of hypertensio ... Full text Link to item Cite

A Framework for Safety Evaluation Throughout the Product Development Life-Cycle.

Journal article Ther Innov Regul Sci · July 2020 Evaluation of the safety profile of medicines is moving from a more reactive approach, where safety experts and statisticians have been primarily focusing on the review of clinical trial data and spontaneous reports, to a more proactive endeavor with cross ... Full text Open Access Link to item Cite

Incidence and Factors Associated With Major Amputation in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Journal article Circ Cardiovasc Qual Outcomes · July 2020 BACKGROUND: Peripheral artery disease (PAD) is associated with increased risk of mortality, cardiovascular morbidity, and major amputation. Data on major amputation from a large randomized trial that included a substantial cohort of patients without critic ... Full text Link to item Cite

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

Journal article N Engl J Med · April 9, 2020 BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. M ... Full text Link to item Cite

Design and analytic considerations for using patient-reported health data in pragmatic clinical trials: report from an NIH Collaboratory roundtable.

Journal article J Am Med Inform Assoc · April 1, 2020 Pragmatic clinical trials often entail the use of electronic health record (EHR) and claims data, but bias and quality issues associated with these data can limit their fitness for research purposes particularly for study end points. Patient-reported healt ... Full text Open Access Link to item Cite

Time for NIH to lead on data sharing.

Journal article Science · March 20, 2020 Full text Link to item Cite

Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease.

Journal article J Am Coll Cardiol · February 18, 2020 BACKGROUND: Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD. OBJECTIVES: The aim of this post hoc analysis was to evaluate sex-specific differences in MACE and l ... Full text Link to item Cite

Major bleeding in patients with peripheral artery disease: Insights from the EUCLID trial.

Journal article Am Heart J · February 2020 BACKGROUND: Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors ... Full text Open Access Link to item Cite

Presenting Risks and Benefits: Helping the Data Monitoring Committee Do Its Job.

Journal article Ann Intern Med · January 21, 2020 Data monitoring committees (DMCs), or data and safety monitoring boards, protect clinical trial participants by conducting benefit-risk assessments during the course of a clinical trial. These evaluations may be improved by broader access to data and more ... Full text Open Access Link to item Cite

The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.

Journal article J Alzheimers Dis · 2020 BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the A ... Full text Open Access Link to item Cite

Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation.

Journal article N Engl J Med · November 14, 2019 BACKGROUND: Optical sensors on wearable devices can detect irregular pulses. The ability of a smartwatch application (app) to identify atrial fibrillation during typical use is unknown. METHODS: Participants without atrial fibrillation (as reported by the ... Full text Open Access Link to item Cite

Open science: The open clinical trials data journey.

Journal article Clin Trials · October 2019 Open data sharing and access has the potential to promote transparency and reproducibility in research, contribute to education and training, and prompt innovative secondary research. Yet, there are many reasons why researchers don't share their data. Thes ... Full text Open Access Link to item Cite

Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial.

Journal article Vasc Med · October 2019 In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients w ... Full text Open Access Link to item Cite

Impact of Procedural Bleeding in Peripheral Artery Disease: An Analysis From EUCLID Trial.

Journal article Circ Cardiovasc Interv · October 2019 BACKGROUND: The relationship between invasive vascular procedures and bleeding in patients with peripheral artery disease has not been well described in the literature. This post hoc analysis from the EUCLID trial (Examining Use of Ticagrelor in Peripheral ... Full text Open Access Link to item Cite

Acute Limb Ischemia in Peripheral Artery Disease.

Journal article Circulation · August 13, 2019 BACKGROUND: Acute limb ischemia (ALI) is an important clinical event and an emerging cardiovascular clinical trial outcome. Risk factors for and outcomes after ALI have not been fully evaluated. METHODS: EUCLID (Examining Use of Ticagrelor in Peripheral Ar ... Full text Open Access Link to item Cite

Correction

Journal article Journal of the American College of Cardiology · July 2019 Full text Cite

Stroke in Patients With Peripheral Artery Disease.

Journal article Stroke · June 2019 Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke an ... Full text Open Access Link to item Cite

Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial.

Journal article JAMA Cardiol · March 1, 2019 IMPORTANCE: It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. O ... Full text Link to item Cite

Incidence, Characteristics, and Outcomes of Myocardial Infarction in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Journal article JAMA Cardiol · January 1, 2019 IMPORTANCE: Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI). OBJECTIVE: To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of M ... Full text Open Access Link to item Cite

Sharing clinical trial data for research purposes.

Journal article Innovations & Thérapeutiques en Oncologie · 2019 Full text Open Access Cite

Cardiovascular and Limb Outcomes in Patients With Diabetes and Peripheral Artery Disease: The EUCLID Trial.

Journal article J Am Coll Cardiol · December 25, 2018 BACKGROUND: Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on ... Full text Open Access Link to item Cite

Ticagrelor versus clopidogrel in patients with symptomatic peripheral artery disease and prior coronary artery disease: Insights from the EUCLID trial.

Journal article Vasc Med · December 2018 Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular morbidity and mortality. We sought to evaluate the risk of concomitant coronary artery disease (CAD) in patients with symptomatic PAD versus PAD without diagnosed CAD, a ... Full text Open Access Link to item Cite

Moving Data Sharing Forward: The Launch of the Vivli Platform

Journal article NAM Perspectives · November 19, 2018 Full text Open Access Cite

Polyvascular Disease and Risk of Major Adverse Cardiovascular Events in Peripheral Artery Disease: A Secondary Analysis of the EUCLID Trial.

Journal article JAMA Netw Open · November 2, 2018 IMPORTANCE: The effect of polyvascular disease on cardiovascular outcomes in the background of peripheral artery disease (PAD) is unclear. OBJECTIVE: To determine the risk of ischemic events (both cardiac and limb) among patients with PAD and polyvascular ... Full text Open Access Link to item Cite

Cardiovascular Outcomes After Lower Extremity Endovascular or Surgical Revascularization: The EUCLID Trial.

Journal article J Am Coll Cardiol · October 2, 2018 BACKGROUND: Lower extremity revascularization (LER) is a common treatment in patients with peripheral artery disease (PAD), but long-term outcomes are poorly defined. OBJECTIVES: The aim was to analyze LER in the EUCLID (Examining Use of tiCagreLor In paD) ... Full text Open Access Link to item Cite

Transforming the future of health together: The Learning Health Systems Consensus Action Plan.

Journal article Learn Health Syst · July 2018 The Learning Health Community is an emergent global multistakeholder grassroots incipient movement bonded together by a set of consensus Core Values Underlying a National-Scale Person-Centered Continuous Learning Health System developed at the 2012 Learnin ... Full text Open Access Link to item Cite

Outcomes of Patients with Critical Limb Ischaemia in the EUCLID Trial.

Journal article Eur J Vasc Endovasc Surg · January 2018 OBJECTIVES: Critical limb ischaemia (CLI) implies an increased risk of cardiovascular morbidity and mortality, and the optimal antithrombotic treatment is not established. DESIGN, MATERIALS, METHODS: The EUCLID trial investigated the effect of monotherapy ... Full text Open Access Link to item Cite

Statistical controversies in clinical research: data access and sharing-can we be more transparent about clinical research? Let's do what's right for patients.

Journal article Ann Oncol · August 1, 2017 Calls for greater transparency and 'open data access' in clinical research are widespread, from sources including the Executive Office of the President, which in 2013 called for increased access to the results of federally funded research. In 2015, The Ins ... Full text Open Access Link to item Cite

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.

Journal article Lancet · May 6, 2017 BACKGROUND: Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but ca ... Full text Open Access Link to item Cite

SPIRIT 2013 statement: Defining standard protocol items for clinical trials

Journal article Japanese Pharmacology and Therapeutics · January 1, 2017 Cite

Data Sharing at a Crossroads.

Journal article N Engl J Med · September 22, 2016 Full text Open Access Link to item Cite

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

Journal article Rev Panam Salud Publica · December 2015 The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic developmen ... Link to item Cite

Bumps and bridges on the road to responsible sharing of clinical trial data.

Journal article Clin Trials · February 2014 BACKGROUND: Sharing data from clinical trials could assist with the advancement of science and medicine, potentially providing a better understanding of both the benefits and risks of medicines and other treatments. Sharing data also allows for questions t ... Full text Open Access Link to item Cite

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

Journal article Ann Intern Med · February 5, 2013 The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic developmen ... Full text Open Access Link to item Cite

Spirit 2013 statement: Defining standard protocol items for clinical trials

Journal article Chinese Journal of Evidence Based Medicine · January 1, 2013 Full text Cite

Statisticians in the Pharmaceutical Industry: The 21st Century

Journal article Statistics in Biopharmaceutical Research · May 2010 Full text Cite

Public disclosure of clinical research.

Journal article Lancet · April 18, 2009 Full text Link to item Cite

Public disclosure of clinical trial results: A necessary step on the path to transparency and trust

Journal article Pharmaceutical Medicine · January 1, 2009 A premise of modern medical practice is that scientific knowledge about health and disease - and the thoughtful application of this information by healthcare providers and patients - will improve health and well-being. Informed decisions about healthcare, ... Full text Cite

The GSK Clinical Study Results Database: Site Utilization Metrics for a Large Public Database

Journal article Therapeutic Innovation Regulatory Science · January 1, 2008 Background: Establishing additional mechanisms for providing public information on clinical studies being conducted and results from completed clinical trials is a topic of significant public debate. This report provides the experience to date with utiliza ... Full text Cite

Reasons for optimism not disillusionment.

Journal article J R Soc Med · September 2006 Full text Link to item Cite

To the editor [11]

Journal article New England Journal of Medicine · March 30, 2006 Cite

Clinical trials report card

Journal article NEW ENGLAND JOURNAL OF MEDICINE · March 30, 2006 Link to item Cite

Clinical Trials Report Card

Journal article New England Journal of Medicine · March 30, 2006 Full text Cite

Clinical trials registration.

Journal article PLoS Med · March 2006 Full text Open Access Link to item Cite

The Society for Clinical Trials opposes US legislation to permit marketing of unproven medical therapies for seriously ill patients.

Journal article Clin Trials · 2006 The proposed Bill S.1956 is a bad law. Wide early access to minimally tested treatments cannot be expected to lead to better or more compassionate care of the seriously ill patient. The long history of medicine is replete with treatments that initially see ... Full text Link to item Cite

Multicentre trials: Foreword

Journal article Statistical Methods in Medical Research · June 1, 2005 Full text Cite

Multicentre trials

Journal article Statistical Methods in Medical Research · June 2005 Full text Cite

Liability issues for data monitoring committee members.

Journal article Clin Trials · 2004 In randomized clinical trials, a data monitoring committee (DMC) is often appointed to review interim data to determine whether there is early convincing evidence of intervention benefit, lack of benefit or harm to study participants. Because DMCs bear ser ... Full text Open Access Link to item Cite

Issues in regulatory guidelines for data monitoring committees.

Journal article Clin Trials · 2004 As clinical trials have emerged as the major research method for evaluating new interventions, the process for monitoring intervention safety and benefit has also evolved. The Data Monitoring Committee (DMC) has become the standard approach to implement th ... Full text Open Access Link to item Cite

Industry perspectives on ICH guidelines.

Journal article Stat Med · October 15, 2002 In 1990 the International Conference on Harmonization (ICH) effort was begun with the intent of standardizing the drug registration and approval process. The need to rationalize and harmonize regulation was driven by concerns over rising costs of health ca ... Full text Link to item Cite

Response from GlaxoSmithKline

Journal article British Journal of Psychiatry · June 2002 Full text Cite

SSRIs and deliberate self-harm.

Journal article Br J Psychiatry · June 2002 Full text Link to item Cite

Estimation of the combined response to treatment in multicenter trials.

Journal article J Biopharm Stat · November 2001 Analyses of multicenter trials consider the estimated treatment effect differences of the individual centers and combine them into an estimate of the overall treatment effect. There has been much debate in the literature concerning the best way to combine ... Link to item Cite

The impact of the international guideline entitled Statistical Principles for Clinical Trials (ICH E9).

Journal article Stat Med · September 15, 2001 At the time of writing, the ICH E9 Note for Guidance entitled "Statistical principles for clinical trials" has been in force in Europe, Japan and the U.S.A. for almost a year. The purpose of this paper is to review the initial progress of E9 in terms of it ... Full text Link to item Cite

Strategic use of statistical thinking in drug development.

Journal article Stat Med · December 15, 2000 The role of the statistician and statistical thinking in the pharmaceutical industry has evolved greatly in the last four or five decades. Regulatory developments and the changing face of the science of drug development have driven this evolution. The incr ... Full text Open Access Link to item Cite

Guidelines for quality assurance in multicenter trials: a position paper.

Journal article Control Clin Trials · October 1998 In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress ... Full text Link to item Cite

An approach to the assessment of therapeutic drug interactions with fixed combination drug products.

Journal article J Biopharm Stat · July 1996 Several complex clinical and statistical issues are involved in the development of a combination drug product. The medical rationale for the combination, the intended clinical use, drug-drug interactions, and dose response are just a few of the considerati ... Full text Link to item Cite

Data monitoring and interim analyses in the pharmaceutical industry: ethical and logistical considerations.

Journal article Stat Med · March 1993 The characteristics of data monitoring and the need for the use of data monitoring committees in clinical trials sponsored by the pharmaceutical industry differ from those of trials sponsored by government. Data monitoring is a continuous process in indust ... Full text Open Access Link to item Cite

Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia.

Journal article Crit Care Med · January 1993 OBJECTIVES: To determine whether a continuous i.v. infusion of cimetidine, a histamine-2 (H2) receptor antagonist, is needed to prevent upper gastrointestinal (GI) hemorrhage when compared with placebo and if that usage is associated with an increased risk ... Full text Open Access Link to item Cite

Comparison of Cimetidine and Placebo for the Prophylaxis of Upper Gastrointestinal Bleeding Due to Stress-related Gastric Mucosal Damage in the Intensive Care Unit

Journal article Journal of Intensive Care Medicine · January 1, 1990 A multicenter, randomized, double-blind, placebo- controlled study was conducted with 87 patients in in tensive care units to study the effectiveness of constant infusions of cimetidine (50 mg/hr) in the prophylaxis of stress-related mucosal bleeding. Fift ... Full text Cite

Cimetidine 800 mg twice daily for healing erosions and ulcers in gastroesophageal reflux disease.

Journal article J Clin Gastroenterol · 1990 Although H2-receptor antagonists have been the mainstay of therapy for gastroesophageal reflux disease (GERD), none of these agents has been approved by the FDA as effective in healing lesions. Since proton pump inhibitors may be associated with long-term ... Full text Link to item Cite

Acute treatment of benign gastric ulcer with once-daily bedtime dosing of cimetidine compared with placebo.

Journal article Aliment Pharmacol Ther · December 1989 This multicentre, double-blind study evaluated the efficacy of cimetidine 800 mg nocte compared to placebo for ulcer healing and pain relief in patients with endoscopically confirmed, benign gastric ulcers treated for up to 8 weeks. Cimetidine accelerated ... Full text Link to item Cite

Beneficial effects of pinacidil on blood lipids: comparisons with prazosin and placebo in patients with hypertension. Pinacidil-Prazosin and Pinacidil-Placebo Research Groups, Lilly Research Laboratories.

Journal article J Lab Clin Med · December 1989 In two randomized, double-blind clinical trials comparing pinacidil with prazosin and with placebo in patients with hypertension, a number of statistically significant and potentially beneficial effects on blood lipids were detected in the patients taking ... Link to item Cite

Reduction of indomethacin induced gastroduodenal mucosal injury and gastrointestinal symptoms with cimetidine in normal subjects.

Journal article J Rheumatol · September 1989 A study was performed in 57 healthy volunteers to determine the effectiveness of cimetidine on reducing gastrointestinal (GI) mucosal lesions and symptoms induced by indomethacin. Endoscopic evidence of gastroduodenal injury and various GI symptoms appeare ... Link to item Cite

Dose-effect and concentration-effect relationships of pinacidil and hydrochlorothiazide in hypertension.

Journal article Clin Pharmacol Ther · August 1989 To determine dose-effect and concentration-effect relationships in hypertension for pinacidil and hydrochlorothiazide when given alone and together, we conducted a randomized, double-blind, 4 X 3 factorial, modified fixed-dose multicenter trial. Three hund ... Full text Link to item Cite

Comparison between continuous and intermittent infusion regimens of cimetidine in ulcer patients.

Journal article Clin Pharmacol Ther · August 1989 The relative effectiveness of intermittent infusions and primed continuous infusions of cimetidine in the maintenance of intragastric pH greater than or equal to 4.0 was evaluated in a double-blind crossover trial in 26 patients who had active or healed ga ... Full text Link to item Cite

Monitoring versus interim analysis of clinical trials: a perspective from the pharmaceutical industry.

Journal article Control Clin Trials · March 1989 The definitions of "interim analysis" and "monitoring" of clinical trials are often ambiguous in the current literature. The resulting confusion can lead to erroneous conclusions and misguided decisions, especially when activities that are operational or o ... Full text Link to item Cite

Antihypertensive effectiveness of very low doses of hydrochlorothiazide: results of the PHICOG Trial.

Journal article Clin Ther · 1989 A large, multicenter, randomized, placebo-controlled, double-blind trial was carried out to determine the effects of the lowest dose of commercially available hydrochlorothiazide. Thus, Dyazide (which contains 25 mg of hydrochlorothiazide and 50 mg of tria ... Link to item Cite

Efficacy of once-daily cimetidine in preventing recurrence of duodenal ulcer.

Journal article Clin Ther · 1989 In a prospective multicenter trial, 88 patients with acute duodenal ulcers that were healed with ranitidine were randomly assigned to receive maintenance treatment with either cimetidine 400 mg (n = 45) or placebo (n = 43) at bedtime for six months. Ten pe ... Link to item Cite

Clinical pharmacokinetics of pinacidil, a potassium channel opener, in hypertension.

Journal article J Clin Pharmacol · January 1989 Pinacidil is a potassium channel opener that decreases blood pressure by reducing peripheral arterial resistance. In two multicenter trials, we studied the concentrations and apparent clearance of pinacidil (406 patients) and concentrations of its pyridyl- ... Full text Link to item Cite

Once-daily bedtime dosing regimen of cimetidine in the treatment of gastric ulcer.

Journal article Clin Ther · 1989 In a double-blind study of 163 patients with benign chronic gastric ulcer, 83 were randomly assigned to receive 800 mg of cimetidine once daily at bedtime for six weeks and 80 received placebo. After six weeks of treatment, the ulcers were healed in 76% of ... Link to item Cite

The efficacy of cimetidine in the treatment of "resistant" duodenal ulcers.

Journal article Clin Ther · 1989 In a prospective multicenter trial, 43 patients with acute duodenal ulcers unhealed after four weeks of treatment with an H2-receptor antagonist, ranitidine, were switched to treatment with another H2-receptor antagonist, cimetidine. Sixty-eight percent of ... Link to item Cite

Vasodilator monotherapy in the treatment of hypertension: comparative efficacy and safety of pinacidil, a potassium channel opener, and prazosin.

Journal article Clin Pharmacol Ther · July 1988 We compared antihypertensive effects of monotherapy with pinacidil (N = 197) or prazosin (N = 204) in a randomized, parallel, double-blind dose-titration study in which hydrochlorothiazide or propranolol could be added for adverse events or lack of efficac ... Full text Link to item Cite

Factorial design. An approach to the assessment of therapeutic drug interactions in clinical trials

Journal article Journal of Clinical Research and Drug Development · January 1, 1988 Factorial design is a useful experimental model for evaluating therapeutic drug interaction in clinical trials. Such a design was used to study interactions of pinacidil, a vasodilator, and hydrochlorothiazide, a diuretic, in hypertension. This paper descr ... Cite

A double-blind study comparing benoxaprofen, aspirin, and benoxaprofen plus aspirin in patients with rheumatoid arthritis.

Journal article Eur J Rheumatol Inflamm · 1982 Ten patients with rheumatoid arthritis completed a study that consisted of 30-day treatment periods with aspirin, benoxaprofen, and benoxaprofen plus aspirin. There were two-week placebo washouts between each treatment. The patients were evaluated biweekly ... Link to item Cite

Clinical pharmacology of benoxaprofen.

Journal article Eur J Rheumatol Inflamm · 1982 Eating does not modify benoxaprofen blood concentrations. Combining benoxaprofen with tolbutamide does not significantly change plasma glucose, insulin, or tolbutamide concentrations. Probenecid, by blocking renal tubular secretion of benoxaprofen, increas ... Link to item Cite

Cellular electrophysiology of clofilium, a new antifibrillatory agent, in normal and ischemic canine Purkinje fibers.

Journal article J Cardiovasc Pharmacol · 1981 Intracellular electrophysiological studies were performed on isolated canine cardiac tissues to investigate further the reported ability of clofilium (3 X 10(-8)--10(-6) M) to selectively increase action potential duration (APD) and refractoriness. In Purk ... Full text Open Access Link to item Cite

Methods of Discrimination Among Stochastic Models of the Negative Binomial Distribution with an Application to Medical Statistics

Journal article Biometrical Journal · January 1981 AbstractThe Negative Binomial Distribution (NBD) can be derived from several underlying stochastic processes. For the NBD to be useful in practice as a descriptive model, it would be of interest to know which underlying pro ... Full text Open Access Cite

Gastrointestinal microbleeding: comparisons between benoxaprofen and other nonsteroidal antiinflammatory agents.

Journal article J Rheumatol Suppl · 1980 Unlike other nonsteroidal antiinflammatory agents, benoxaprofen has only minor antiprostaglandin synthetase activity. This property may explain the lack of gastric irritation seen in animal studies. To evaluate gastric irritation in man, benoxaprofen was c ... Link to item Cite

An analysis of returning patients in family practice.

Journal article J Fam Pract · May 1979 Morbidity records from eight practices participating for three years in the Virginia Family Practice Data System are analyzed with respect to two mutually exclusive groups of patients: those who return from one year to the next and those who do not return. ... Link to item Cite

Family practice in Virginia: a comparative analysis of two years' data.

Journal article J Fam Pract · April 1978 Data representing Fiscal Years 1975 and 1976 as well as the aggregate 1975--1976 data set are reviewed in this paper. Information on 92,410 discrete patients and the 333,709 transactions they generated is studied. The transactions per patient rate of 3.6 v ... Link to item Cite

The Age/Sex Register: estimation of the practice population.

Journal article J Fam Pract · December 1977 Determination of the number of patients served by a family practice is important for health services delivery and research. A sound estimate of the practice population should enhance the patient management responsibilities of the family physician. This met ... Link to item Cite