Real-world data in the molecular era-finding the reality in the real world.

Published on Feb 1, 2016in Clinical Pharmacology & Therapeutics6.565
· DOI :10.1002/CPT.300
Dane J. Dickson1
Estimated H-index: 1
John D. Pfeifer55
Estimated H-index: 55
(WashU: Washington University in St. Louis)
Real-world data (RWD) promises to provide a pivotal element to the understanding of personalized medicine. However, without true representation (or the reality) of the patient-disease biosystem and its molecular contributors, RWD may hamper rather than help this advancement. In this review article, we discuss RWD vs. clinical reality and the disconnects that exist currently (emphasizing molecular medicine), and methods of closing the gaps between RWD and reality.
📖 Papers frequently viewed together
2016PSB: Pacific Symposium on Biocomputing
3 Citations
11 Citations
65 Citations
#1Sinchita Roy-Chowdhuri (University of Texas MD Anderson Cancer Center)H-Index: 27
#2Rashmi S. Goswami (University of Texas MD Anderson Cancer Center)H-Index: 14
Last. John Stewart (University of Texas MD Anderson Cancer Center)H-Index: 32
view all 14 authors...
BACKGROUND The use of cytology specimens for next-generation sequencing (NGS) is particularly challenging because of the unconventional substrate of smears and the often limited sample volume. An analysis of factors affecting NGS testing in cytologic samples may help to increase the frequency of successful testing. METHODS This study reviewed variables associated with all in-house cytology cases (n = 207) that were analyzed by NGS with the Ion Torrent platform during a 10-month interval. A stati...
93 CitationsSource
#1Paula S. Ramos (MUSC: Medical University of South Carolina)H-Index: 17
#2Andrew M. Shedlock (MUSC: Medical University of South Carolina)H-Index: 7
Last. Carl D. Langefeld (Wake Forest University)H-Index: 105
view all 3 authors...
Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. Collectively, ADs are common, exhibit gender and ethnic disparities, and increasing incidence. As natural selection is an important influence on human genetic variation, and immune function...
82 CitationsSource
#1Maria Chiara Chindamo (UFRJ: Federal University of Rio de Janeiro)H-Index: 4
#2Vera L Nunes-Pannain (UFRJ: Federal University of Rio de Janeiro)H-Index: 1
Last. Renata M. Perez (UFRJ: Federal University of Rio de Janeiro)H-Index: 19
view all 7 authors...
Background and aims. The prediction of intermediate stage of fibrosis in chronic hepatitis C represents a prognostic factor for disease progression. Studies evaluating biopsy performance in intermediate stage considering current patterns of liver samples and pathologists’ variability are scarce. We aimed to evaluate the effect of optimal liver specimens (≥ 20 mm and/or ≥ 11 portal tracts) and pathologists’ expertise on agreement for intermediate stage of fibrosis in chronic hepatitis C. Material...
7 CitationsSource
#1George J Burghel (St James's University Hospital)H-Index: 7
#2Carolyn D. HurstH-Index: 24
Last. Margaret A. KnowlesH-Index: 83
view all 7 authors...
Detection of clinically actionable mutations in diagnostic tumour specimens aids in the selection of targeted therapeutics. With an ever increasing number of clinically significant mutations identified, tumour genetic diagnostics is moving from single to multigene analysis. As it is still not feasible for routine diagnostic laboratories to perform sequencing of the entire cancer genome, our approach was to undertake targeted mutation detection. To optimise our diagnostic workflow, we evaluated t...
12 CitationsSource
#1Timothy D. O’Brien (Vandy: Vanderbilt University)H-Index: 4
#2Peilin Jia (Vandy: Vanderbilt University)H-Index: 32
Last. Zhongming Zhao (Vandy: Vanderbilt University)H-Index: 70
view all 16 authors...
Abstract Whole exome sequencing (WES) and RNA sequencing (RNA-Seq) are two main platforms used for next-generation sequencing (NGS). While WES is primarily for DNA variant discovery and RNA-Seq is mainly for measurement of gene expression, both can be used for detection of genetic variants, especially single nucleotide variants (SNVs). How consistently variants can be detected from WES and RNA-Seq has not been systematically evaluated. In this study, we examined the technical and biological inco...
23 CitationsSource
#1Yuan Qi (University of Texas MD Anderson Cancer Center)H-Index: 20
#2Xiuping Liu (University of Texas MD Anderson Cancer Center)H-Index: 25
Last. Lajos Pusztai (Yale University)H-Index: 108
view all 8 authors...
Nucleotide alterations detected by next generation sequencing are not always true biological changes but could represent sequencing errors. Even highly accurate methods can yield substantial error rates when applied to millions of nucleotides. In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.2 Mb) using the SOLiD v4 platform....
12 CitationsSource
#1Ashwin Belle (UM: University of Michigan)H-Index: 11
#2Raghuram Thiagarajan (UM: University of Michigan)H-Index: 5
Last. Kayvan NajarianH-Index: 25
view all 6 authors...
The rapidly expanding field of big data analytics has started to play a pivotal role in the evolution of healthcare practices and research. It has provided tools to accumulate, manage, analyze, and assimilate large volumes of disparate, structured, and unstructured data produced by current healthcare systems. Big data analytics has been recently applied towards aiding the process of care delivery and disease exploration. However, the adoption rate and research development in this space is still ...
246 CitationsSource
The scaling up of data in clinical pharmacology and the merger of systems biology and pharmacology has led to the emergence of a new discipline of Quantitative and Systems Pharmacology (QSP). This new research direction might significantly advance the discovery, development and clinical use of therapeutic drugs. Research communities from computational biology, systems biology and biological engineering—working collaboratively with pharmacologists, geneticists, biochemists and analytical chemists...
108 CitationsSource
#1Glen J. Weiss (Cancer Treatment Centers of America)H-Index: 51
#2Hoff Br (Cancer Treatment Centers of America)H-Index: 1
Last. Khemka (Cancer Treatment Centers of America)H-Index: 1
view all 11 authors...
Background It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid...
22 CitationsSource
#1Siân JonesH-Index: 37
#2Valsamo Anagnostou (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 32
Last. Luis A. Diaz (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 120
view all 18 authors...
Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues,...
287 CitationsSource
Cited By7
#1Patricia A. DeverkaH-Index: 25
#2Michael P. Douglas (UCSF: University of California, San Francisco)H-Index: 18
Last. Kathryn A. Phillips (UCSF: University of California, San Francisco)H-Index: 56
view all 3 authors...
Abstract Objective Given the potential of real-world evidence (RWE) to inform understanding of the risk–benefit profile of next-generation sequencing (NGS)–based testing, we undertook a study to describe the current landscape of whether and how payers use RWE as part of their coverage decision making and potential solutions for overcoming barriers. Methods We performed a scoping literature review of existing RWE evidentiary frameworks for evaluating new technologies and identified barriers to cl...
6 CitationsSource
: Reality is defined as a real event, a real thing, or state of affairs. Reality exists in the places where we live our daily lives, in the relationships we have with others, and in our experiences, circumstances, and situations that occur across the lifespan. As the everydayness of our lives becomes increasingly digitized, data generated from the reality that exists outside of our healthcare encounters holds much promise to fill recognized gaps in real-world evidence (RWE). In the past decade, ...
4 CitationsSource
#1Joshua R. Lewis (USYD: University of Sydney)H-Index: 30
#2Wendy Lipworth (USYD: University of Sydney)H-Index: 20
Last. Ian Kerridge (USYD: University of Sydney)H-Index: 38
view all 3 authors...
Although randomized controlled trials remain the scientific ideal for determining the efficacy and safety of new treatments, they are sometimes insufficient to address the evidentiary requirements of regulators and payers. This is particularly the case when it comes to precision medicines because trials are often small, deliver incomplete insights into outcomes of most interest to policymakers (eg, overall survival), and may fail to address other complex diagnostic and treatment-related question...
8 CitationsSource
#1Edoardo Mannucci (UniFI: University of Florence)H-Index: 98
#2Ele FerranniniH-Index: 110
6 CitationsSource
#1Wendy Lipworth (USYD: University of Sydney)H-Index: 20
#2Paul H. Mason (USYD: University of Sydney)H-Index: 13
Last. John P. A. Ioannidis (Stanford University)H-Index: 204
view all 4 authors...
Biomedical innovation and translation are increasingly emphasizing research using “big data.” The hope is that big data methods will both speed up research and make its results more applicable to “real-world” patients and health services. While big data research has been embraced by scientists, politicians, industry, and the public, numerous ethical, organizational, and technical/methodological concerns have also been raised. With respect to technical and methodological concerns, there is a view...
29 CitationsSource
#1Elliott M. Antman (Brigham and Women's Hospital)H-Index: 174
#2Joseph Loscalzo (Brigham and Women's Hospital)H-Index: 148
Both the cardiovascular research and clinical communities are ideally positioned to develop and implement precision medicine to achieve more effective prevention and treatment. This Review highlights the advances in modern biomedicine that make possible the precision medicine era, provides current examples of the use of this approach in the cardiovascular field, and defines the goals and barriers to implementation of a precision medicine system.
116 CitationsSource
#1Dong JiH-Index: 10
#2Guofeng ChenH-Index: 9
Last. George K. K. LauH-Index: 79
view all 15 authors...
Background Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis.
13 CitationsSource