The Potential for Therapeutic Misconception in Pulmonary Arterial Hypertension Clinical Trials: A Case-Based Discussion

2010 ◽  
Vol 9 (4) ◽  
pp. 220-222
Author(s):  
David B. Badesch ◽  
Marilyn E. Coors ◽  
Deborah H. McCollister ◽  
Todd Bull ◽  
Alison Lakin
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Conflicts Of Interest ◽  
Medical Knowledge ◽  
Study Drug ◽  
Clinical Equipoise ◽  
Therapeutic Misconception ◽  
Pulmonary Arterial

This case study illustrates several of the potential challenges frequently encountered by clinical investigators working in the area of pulmonary arterial hypertension (PAH). It raises the issues of therapeutic misconception and clinical equipoise, and illustrates the importance of informing potential research participants of all their options in explicit detail.20 It also emphasizes the importance of explaining to patients that they are being asked to participate in a study to advance medical knowledge and develop therapies for the population of patients with PAH, and not for their own benefit. While they may benefit from the study drug, if they in fact receive it, this should not be offered as a reason for their potential participation. In addition, investigators should disclose any potential conflicts of interest to potential participants. During the past 2 decades, such clinical trials have advanced the treatment of patients with PAH and continue to offer the possibility of further improvements in our treatment of this devastating disease.

A Semi-Automated Term Harmonization Pipeline Applied to Pulmonary Arterial Hypertension Clinical Trials

2021 ◽  
Author(s):  
Ryan J. Urbanowicz ◽  
John H. Holmes ◽  
Dina Appleby ◽  
Vanamala Narasimhan ◽  
Stephen Durborow ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
System Organ Class ◽  
High Level Group ◽  
Fuzzy Matching ◽  
Pulmonary Arterial ◽  
High Level ◽  
Level Group ◽  
System Organ

Abstract Objective Data harmonization is essential to integrate individual participant data from multiple sites, time periods, and trials for meta-analysis. The process of mapping terms and phrases to an ontology is complicated by typographic errors, abbreviations, truncation, and plurality. We sought to harmonize medical history (MH) and adverse events (AE) term records across 21 randomized clinical trials in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Methods We developed and applied a semi-automated harmonization pipeline for use with domain-expert annotators to resolve ambiguous term mappings using exact and fuzzy matching. We summarized MH and AE term mapping success, including map quality measures, and imputation of a generalizing term hierarchy as defined by the applied Medical Dictionary for Regulatory Activities (MedDRA) ontology standard. Results Over 99.6% of both MH (N = 37,105) and AE (N = 58,170) records were successfully mapped to MedDRA low-level terms. Automated exact matching accounted for 74.9% of MH and 85.5% of AE mappings. Term recommendations from fuzzy matching in the pipeline facilitated annotator mapping of the remaining 24.9% of MH and 13.8% of AE records. Imputation of the generalized MedDRA term hierarchy was unambiguous in 85.2% of high-level terms, 99.4% of high-level group terms, and 99.5% of system organ class in MH, and 75% of high-level terms, 98.3% of high-level group terms, and 98.4% of system organ class in AE. Conclusion This pipeline dramatically reduced the burden of manual annotation for MH and AE term harmonization and could be adapted to other data integration efforts.

Enrichment Benefits of Risk Algorithms for Pulmonary Arterial Hypertension Clinical Trials

2020 ◽  
Author(s):  
Jacqueline V. Scott ◽  
Christine E. Garnett ◽  
Manreet K. Kanwar ◽  
Norman L. Stockbridge ◽  
Raymond L. Benza
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arterial

scholarly journals Novel Therapeutic Approaches of Pulmonary Arterial Hypertension

2019 ◽  
Vol 28 (02) ◽  
pp. 112-117
Author(s):  
Sanjay Tyagi ◽  
Vishal Batra
Keyword(s):  
Nitric Oxide ◽  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Endothelin Receptors ◽  
Pulmonary Vasculature ◽  
Therapeutic Approaches ◽  
Uncommon Disease ◽  
Pulmonary Arterial ◽  
Novel Therapeutic

AbstractPulmonary arterial hypertension (PAH) is an uncommon disease characterized progressive remodeling of pulmonary vasculature. Although treatment for PAH have improved in last two decades but the outcome remains fatal. Currently, the therapies for PAH target three well-established pathways the nitric oxide (NO) pathway, endothelin receptors, and prostanoids. There are multiple potential targets for development of newer drugs in PAH which requires meticulous research and clinical trials.

scholarly journals Measures of Response in Clinical Trials of Systemic Sclerosis: The Combined Response Index for Systemic Sclerosis (CRISS) and Outcome Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis (EPOSS)

2009 ◽  
Vol 36 (10) ◽  
pp. 2356-2361 ◽  
Author(s):  
DINESH KHANNA ◽  
OLIVER DISTLER ◽  
JEROME AVOUAC ◽  
FRANK BEHRENS ◽  
PHILIP J. CLEMENTS ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Outcome Measures ◽  
Delphi Process ◽  
Response Index ◽  
Pulmonary Arterial

There have been steady efforts to develop a combined response index for systemic sclerosis (CRISS). A parallel and equally successful effort has been made by an Expert Panel on Outcome Measures in PAH related to Systemic Sclerosis (EPOSS) to measure effect in treatment of pulmonary arterial hypertension of systemic sclerosis (PAH-SSc). CRISS conducted a Delphi process combined with expert review to identify 11 candidate domains for inclusion in a core set of outcomes for SSc clinical trials: soluble biomarkers, cardiac, digital ulcers, gastrointestinal, global health, health related quality of life (HRQOL) and function, musculoskeletal, pulmonary, Raynaud’s, renal, and skin. Tools within domains were also agreed upon. Concentrating on one aspect of disease, PAH, EPOSS also conducted a Delphi process and judged the following domains as the most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure, cardiac function, exercise testing; severity of dyspnea, discontinuation of treatment; quality of life/activities of daily living; global state; and survival. Possible useful tools within each domain were also agreed on. Patient derived, physician derived, and objective measures of response will be included and combined with the idea that each reflects different aspects of PAH (EPOSS) and overall disease (CRISS) although this assumption may not prove true and can be separated if statistically and clinically valid to do so. In either case, prospective studies will require measurement of all domains, and tools are required and will be developed to define appropriate combined measures of response. CRISS and EPOSS are being developed through the OMERACT process. Through Delphi process and literature review significant progress has been made for both indices, and prospective data are being collected.

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