Design of clinical trials in rheumatology

2013 ◽  
Author(s):  
Vibeke Strand ◽  
Jeremy Sokolove ◽  
Alvina D. Chu
Keyword(s):  
Lupus Erythematosus ◽  
Trial Design ◽  
Phase 1 ◽  
Proof Of Concept ◽  
Phase 3 ◽  
Treatment Allocation ◽  
Randomized Controlled ◽  
The Past ◽  
Development And Validation ◽  
Made In

Development of new therapies for rheumatic diseases requires a series of randomized controlled trials (RCTs) progressing from phase 1, 'first-in-human' to generate initial safety, pharmacokinetic (PK) and pharmacodynamic (PD) data; to phase 2, proof of concept for efficacy with safety and PK/PD data; and phase 3, designed to demonstrate definitive efficacy and safety to support regulatory approval. Important aspects of RCT designs include sample size estimations, treatment allocation, rescue, blinding, and statistical analyses of prespecified endpoints to preserve trial integrity. Over the past 15 years, significant progress has been made in the design of RCTs in rheumatoid arthritis (RA). Similarly, development and validation of composite outcome measures in psoriatic arthritis, ankylosing spondylitis, gout, and osteoarthritis have furthered trial design and treatment approvals. RCTs in systemic lupus erythematosus and other multisystem, heterogeneous diseases pose more challenges. Trial design will continue to evolve as promising therapies are introduced into the clinic.

Design of clinical trials in rheumatology

2016 ◽  
Author(s):  
Vibeke Strand ◽  
Jeremy Sokolove ◽  
Alvina D. Chu
Keyword(s):  
Lupus Erythematosus ◽  
Trial Design ◽  
Phase 1 ◽  
Proof Of Concept ◽  
Phase 3 ◽  
Treatment Allocation ◽  
Randomized Controlled ◽  
The Past ◽  
Development And Validation ◽  
Made In

Development of new therapies for rheumatic diseases requires a series of randomized controlled trials (RCTs) progressing from phase 1, ’first-in-human’ to generate initial safety, pharmacokinetic (PK) and pharmacodynamic (PD) data; to phase 2, proof of concept for efficacy with safety and PK/PD data; and phase 3, designed to demonstrate definitive efficacy and safety to support regulatory approval. Important aspects of RCT designs include sample size estimations, treatment allocation, rescue, blinding, and statistical analyses of prespecified endpoints to preserve trial integrity. Over the past 15 years, significant progress has been made in the design of RCTs in rheumatoid arthritis (RA). Similarly, development and validation of composite outcome measures in psoriatic arthritis, ankylosing spondylitis, gout, and osteoarthritis have furthered trial design and treatment approvals. RCTs in systemic lupus erythematosus and other multisystem, heterogeneous diseases pose more challenges. Trial design will continue to evolve as promising therapies are introduced into the clinic.

Design of clinical trials in rheumatology

2018 ◽  
Author(s):  
Vibeke Strand ◽  
Jeremy Sokolove ◽  
Alvina D. Chu
Keyword(s):  
Lupus Erythematosus ◽  
Trial Design ◽  
Phase 1 ◽  
Proof Of Concept ◽  
Phase 3 ◽  
Treatment Allocation ◽  
Randomized Controlled ◽  
The Past ◽  
Development And Validation ◽  
Made In

Development of new therapies for rheumatic diseases requires a series of randomized controlled trials (RCTs) progressing from phase 1, ’first-in-human’ to generate initial safety, pharmacokinetic (PK) and pharmacodynamic (PD) data; to phase 2, proof of concept for efficacy with safety and PK/PD data; and phase 3, designed to demonstrate definitive efficacy and safety to support regulatory approval. Important aspects of RCT designs include sample size estimations, treatment allocation, rescue, blinding, and statistical analyses of prespecified endpoints to preserve trial integrity. Over the past 15 years, significant progress has been made in the design of RCTs in rheumatoid arthritis (RA). Similarly, development and validation of composite outcome measures in psoriatic arthritis, ankylosing spondylitis, gout, and osteoarthritis have furthered trial design and treatment approvals. RCTs in systemic lupus erythematosus and other multisystem, heterogeneous diseases pose more challenges. Trial design will continue to evolve as promising therapies are introduced into the clinic.

Design of clinical trials in rheumatology

2013 ◽  
pp. 227-236
Author(s):  
Vibeke Strand ◽  
Jeremy Sokolove ◽  
Alvina D. Chu
Keyword(s):  
Lupus Erythematosus ◽  
Trial Design ◽  
Phase 1 ◽  
Population Sample ◽  
Phase 2 ◽  
Composite Outcome ◽  
Efficacy And Safety ◽  
Treatment Allocation ◽  
Development And Validation ◽  
Selection Of

Development of new therapies for rheumatic diseases requires a series of randomized controlled trials (RCTs) progressing from phase 1, ’first-in-human’ to generate initial safety, pharmacokinetic (PK) and pharmacodynamic (PD) data; to phase 2, proof of concept for efficacy with safety and PK/PD data; and phase 3, designed to demonstrate definitive efficacy and safety to support regulatory approval. Important aspects of RCT designs include selection of patient population, sample size estimations, treatment allocation, rescue, blinding, and statistical analyses of prespecified endpoints to preserve trial integrity. Over the past 20 years, significant progress has been made in the design of RCTs in rheumatoid arthritis (RA). Similarly, development and validation of composite outcome measures in psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) have furthered trial design and treatment approvals. RCTs in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), vasculitis and other multisystem, heterogeneous diseases pose more challenges. Trial design will continue to evolve as promising therapies are introduced into the clinic and more therapies are approved for each indication.

scholarly journals Connecting Youth and Young Adults to Optimize Antiretroviral Therapy Adherence (YouTHrive): Protocol for a Randomized Controlled Trial

10.2196/11502 ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. e11502 ◽  
Author(s):  
K J Horvath ◽  
R F MacLehose ◽  
A Martinka ◽  
J DeWitt ◽  
L Hightow-Weidman ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Phase 1 ◽  
Art Adherence ◽  
Phase 2 ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Adherence Intervention ◽  
Living With Hiv ◽  
Beta Testing ◽  
Us Cities

Background Despite intensive efforts to engage people living with HIV in the United States, less than half of the youth aged 13 to 24 years achieve viral suppression. There is a clear and continued need for innovative behavioral programs that support optimizing adherence among young persons with HIV. Objective There are 3 phases of this project. Phase 1 involves conducting focus groups to obtain feedback from youth about an existing technology-based antiretroviral therapy (ART) adherence intervention. Phase 2 will be used to conduct beta testing with youth to refine and finalize the YouTHrive (YT) intervention. Phase 3 is a randomized controlled trial (RCT) to test the efficacy of the YT intervention among youth living with HIV (YLWH). Methods In phase 1, we will conduct 6 focus groups with approximately 8 youths (aged 15-19 years) and young adults (aged 20-24 years), each in 3 US cities to obtain (1) feedback from YLWH about the look and feel and content of an existing adult-focused Web-based ART adherence intervention and (2) suggestions for adapting the intervention for YLWH similar to themselves. Phase 2 will involve updating the existing intervention to include features and functionality recommended by YLWH in phase 1; it will conclude with beta testing with 12 participants to gain feedback on the overall design and ensure proper functionality and ease of navigation. For phase 3, we will enroll 300 YLWH in 6 US cities (Atlanta, Chicago, Houston, New York City, Philadelphia, and Tampa) into a 2-arm prospective RCT. Participants will be randomized 1:1 to YT intervention or control group. The randomization sequence will be stratified by city and use random permuted blocks of sizes 2 and 4. Participants randomized to the control condition will view a weekly email newsletter on topics related to HIV, with the exception of ART adherence, for 5 months. Participants randomized to the YT intervention condition will be given access to the YT site for 5 months. Study assessments will occur at enrollment and 5, 8, and 11 months post enrollment. The primary outcome that will be assessed is sustained viral load (VL), defined as the proportion of participants in each study arm who have suppressed VL at both the 5- and 11-month assessment; the secondary outcome that will be assessed is suppressed VL at both the 5- and 11-month assessment between drug-using and nondrug-using participants assigned to the YT intervention arm. Results Participant recruitment began in May 2017 for phase 1 of the study. The data collection for aim 3 is anticipated to end in April 2020. Conclusions The efficacy trial of the YT intervention will help to fill gaps in understanding the efficacy of mobile interventions to improve ART adherence among at-risk populations. Trial Registration ClinicalTrials.gov NCT03149757; https://clinicaltrials.gov/ct2/show/NCT03149757 (Archived by WebCite at http://www.webcitation.org/73pw57Cf1) International Registered Report Identifier (IRRID) DERR1-10.2196/11502

Venous thromboembolism risk with contemporary lenalidomide-based regimes for multiple myeloma: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19503-e19503
Author(s):  
Rajshekhar Chakraborty ◽  
Irbaz Bin Riaz ◽  
Saad Malik ◽  
Naimisha Marneni ◽  
Alex Mejia Garcia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Meta Analysis ◽  
Phase 1 ◽  
Treatment Phase ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Related Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic

e19503 Background: The risk of venous thromboembolic events (VTE) despite mandatory thromboprophylaxis (TPx) in patients with multiple myeloma (MM) receiving contemporary lenalidomide (Len)-based regimens is not well-defined. Methods: Medline, Embase, and CENTRAL databases were queried to identify phase 1-3 clinical trials of Len-based regimens with mandatory TPx published until April 2018. Random effects meta-analysis was performed using CMAv3 software to obtain crude, and per 100 patient-cycle incidence rate (IR). Prespecified subgroup analyses were performed to obtain IR for VTE by (1) line of treatment (newly diagnosed [ND], relapsed/refractory [RR] and maintenance [Mx] phase) and (2) different Len-based regimens. Results: We screened 1069 citations and analyzed data from 43 trials with 8696 patients, including 17 in ND, 23 in RR and 3 in Mx phase. 12 out of 43 were Phase 3 randomized controlled trials. The overall incidence of VTE in 8696 patients was 4.6% (95% CI, 3.7-5.8%), with 1.0 event (95% CI, 0.7-1.4%) per 100 patient cycles. In patients with NDMM (n = 3295), 193 (5.9%) experienced VTE with a pooled IR of 0.9 (95% CI, 0.3-2.3) per 100 patient-cycle. Among RRMM patients (n = 3981), 251 (6.3%) experienced VTE with a pooled IR of 1.0 (95% CI, 0.4-2.3) per 100 patient-cycle. The incidence of VTE was highest with the following triplet regimens: Rd + Proteasome inhibitor (PIs) and Rd + Anthracycline (Ac) [+/- Vincristine], with the latter having a high risk of VTE regardless of the treatment phase (table). With Len Mx (n = 1420), 38 (2.7%) patients had VTE, with a pooled IR of 0.2 (95% CI, 0-2.1) per 100 patient-cycle. Conclusions: Patients with MM undergoing treatment with Len-based regimens remain at risk of VTE despite current TPx strategies. The estimates of VTE IR provided by this analysis can guide clinicians in assessing treatment-related risk of VTE in this setting. [Table: see text]

Gene Therapy for Hemophilia: a review on clinical benefit, limitations and remaining issues

Blood ◽  
2021 ◽  
Author(s):  
Frank W.G. Leebeek ◽  
Wolfgang Miesbach
Keyword(s):  
Gene Therapy ◽  
Clinical Benefit ◽  
Hemophilia A ◽  
Phase 1 ◽  
Successful Outcome ◽  
Severe Hemophilia ◽  
The Past ◽  
Therapy Studies ◽  
The Impact ◽  
Made In

In the past decade enormous progress has been made in the development of gene therapy for hemophilia A and B. After the first encouraging results of intravenously administered AAV-based liver-directed gene therapy in patients with severe hemophilia B were reported in 2011, many gene therapy studies have been initiated. Most of these studies, using AAV vectors with various gene constructs, showed sufficient FVIII and FIX expression in patients to significantly reduce the number of bleeds and the need for prophylaxis in the fast majority of the severe hemophilia patients. This resulted in great clinical benefit for nearly all patients. In this review we will summarize the most recent findings of reported and ongoing gene therapy trials. We will highlight the successful outcome of trials with focus on the results of recently reported phase 1 trials and preliminary results of phase 2b/3 trials for hemophilia A and B. These new reports also reveal the impact of side effects and drawbacks associated with gene therapy. We will therefore also discuss the limitations and remaining issues of the current gene therapy approaches. These issues have to be resolved before gene therapy will be widely available for the hemophilia patient population.

International development and validation of a classification system for the identification of Barrett’s neoplasia using acetic acid chromoendoscopy: the Portsmouth acetic acid classification (PREDICT)

Gut ◽  
2017 ◽  
Vol 67 (12) ◽  
pp. 2085-2091 ◽  
Author(s):  
Kesavan Kandiah ◽  
Fergus J Q Chedgy ◽  
Sharmila Subramaniam ◽  
Gaius Longcroft-Wheaton ◽  
Paul Bassett ◽  
...  
Keyword(s):  
Acetic Acid ◽  
International Development ◽  
Classification System ◽  
Phase 1 ◽  
Oesophageal Adenocarcinoma ◽  
Clinical Value ◽  
Phase 3 ◽  
Established Risk Factor ◽  
Surface Patterns ◽  
Development And Validation

BackgroundBarrett’s oesophagus is an established risk factor for developing oesophageal adenocarcinoma. However, Barrett’s neoplasia can be subtle and difficult to identify. Acetic acid chromoendoscopy (AAC) is a simple technique that has been demonstrated to highlight neoplastic areas but lesion recognition with AAC remains a challenge, thereby hampering its widespread use.ObjectiveTo develop and validate a simple classification system to identify Barrett’s neoplasia using AAC.DesignThe study was conducted in four phases: phase 1—development of component descriptive criteria; phase 2—development of a classification system; phase 3—validation of the classification system by endoscopists; and phase 4—validation of the classification system by non-endoscopists.ResultsPhases 1 and 2 led to the development of a simplified AAC classification system based on two criteria: focal loss of acetowhitening and surface patterns of Barrett’s mucosa. In phase 3, the application of PREDICT (Portsmouth acetic acid classification) by endoscopists improved the sensitivity and negative predictive value (NPV) from 79.3% and 80.2% to 98.1% and 97.4%, respectively (p<0.001). In phase 4, the application of PREDICT by non-endoscopists improved the sensitivity and NPV from 69.6% and 75.5% to 95.9% and 96.0%, respectively (p<0.001).ConclusionWe developed and validated a classification system known as PREDICT for the diagnosis of Barrett’s neoplasia using AAC. The improvement seen in the sensitivity and NPV for detection of Barrett’s neoplasia in phase 3 demonstrates the clinical value of PREDICT and the similar improvement seen among non-endoscopists demonstrates the potential for generalisation of PREDICT once proven in real time.

Study protocols for the development and randomized controlled pilot trial of a patient decision aid to facilitate women's choice between oral and LAI ART for HIV (Preprint)

2021 ◽  
Author(s):  
Morgan M. Philbin ◽  
Tara McCrimmon ◽  
Victoria Shaffer ◽  
Deanna Kerrigan ◽  
Margaret Pereyra ◽  
...  
Keyword(s):  
Decision Making ◽  
Mixed Methods ◽  
Decision Aid ◽  
Phase 1 ◽  
Shared Decision ◽  
Patient Decision Aid ◽  
Phase 3 ◽  
Web Based ◽  
Randomized Controlled ◽  
Patient Decision

BACKGROUND Many women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill-taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women’s adherence and long-term HIV outcomes. OBJECTIVE This study will develop and pilot test a web-based patient decision aid, called i.ART+support (iARTs). This decision aid aims to support shared decision-making between WWH and their providers, and help women choose between oral and LAI HIV treatment. METHODS The study will occur in three phases. In Phase 1, we will utilize a mixed-methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During Phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In Phase 3, i.ARTs will be tested in a randomized controlled trial (RCT) with n=180 women in Miami, FL and assessed for feasibility, usability and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART refills, and clinic attendance. RESULTS Phase 1 participant recruitment began in September 2021. CONCLUSIONS This study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed-methods design, and implementation in a real-world clinical setting. CLINICALTRIAL We will apply for Clinicaltrials.gov registration prior to Phase 3 when we enroll our first participant in the RCT. This is anticipated to occur in April 2023.

scholarly journals Conditional Reasoning: A Review and Suggestions for Future Test Development and Validation

2019 ◽  
Vol 23 (1) ◽  
pp. 65-95 ◽  
Author(s):  
James M. LeBreton ◽  
Elizabeth M. Grimaldi ◽  
Jeremy L. Schoen
Keyword(s):  
Final Section ◽  
Test Development ◽  
Conditional Reasoning ◽  
The Past ◽  
Conference Presentations ◽  
Development And Validation ◽  
Future Test ◽  
Made In

Lawrence R. James spent the last 20 years of his 35-year career developing and validating a new theory of personality that he called conditional reasoning. This theory was focused on mapping and measuring core aspects of the implicit (i.e., unconscious) personality. In this article, we (a) review James’s seminal contributions to the theory and measurement of conditional reasoning, (b) discuss subsequent contributions made in the area of conditional reasoning, and (c) provide a brief “look under the hood” at James’s approach to test development and validation. This final section of our paper is designed to familiarize other researchers with the protocols that James and his colleagues have used over the past 20 years. Many of these protocols have gone unmentioned or only briefly acknowledged (e.g., in conference presentations or informal meetings); indeed, many of these validation protocols were “implicit” in the thinking of James and his approach to the study of personality. Having benefited from working closely with James, we were privy to many of these implicit assumptions and protocols that privately guided James’s early work on conditional reasoning.

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