Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017

[1]  D. Kent,et al.  Testing of CYP2C19 Variants and Platelet Reactivity for Guiding Antiplatelet Treatment , 2013 .

[2]  M. Tétreault,et al.  Whole-exome sequencing as a diagnostic tool: current challenges and future opportunities , 2015, Expert review of molecular diagnostics.

[3]  K. Phillips.  Closing the evidence gap in the use of emerging testing technologies in clinical practice. , 2008, JAMA.

[4]  S. Selph,et al.  Emerging Approaches to Diagnosis and Treatment of Non–Muscle-Invasive Bladder Cancer , 2015 .

[5]  Marc S. Williams,et al.  Evidence synthesis and guideline development in genomic medicine: current status and future prospects , 2014, Genetics in Medicine.

[6]  N. Eriksson,et al.  A randomized trial of genotype-guided dosing of warfarin. , 2013, The New England journal of medicine.

[7]  G. Lyman,et al.  Generating and evaluating evidence of the clinical utility of molecular diagnostic tests in oncology , 2015, Genetics in Medicine.

[8]  B. Coles,et al.  Cancer genetic risk assessment for individuals at risk of familial breast cancer. , 2012, The Cochrane database of systematic reviews.

[9]  Gary H Lyman,et al.  Biomarker Tests for Molecularly Targeted Therapies--The Key to Unlocking Precision Medicine. , 2016, The New England journal of medicine.

[10]  Munir Pirmohamed,et al.  A Randomized Trial of Genotype-Guided Dosing of Warfarin , 2014 .

[11]  Christopher G Chute,et al.  Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol. , 2014, Mayo Clinic proceedings.

[12]  Blue Cross Blue Shield Asssociation.  Noninvasive prenatal cell-free fetal DNA-based screening for aneuploidies other than trisomy 21. , 2014, Technology Evaluation Center Assessment Program. Executive summary.

[13]  Susan L Neuhausen,et al.  Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Virginia G Kaklamani,et al.  Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. , 2015, The New England journal of medicine.

[15]  A. StAteMent.  ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing , 2014, Genetics in Medicine.

[16]  T. Trikalinos,et al.  Systematic Reviews on Selected Pharmacogenetic Tests for Cancer Treatment: CYP2D6 for Tamoxifen in Breast Cancer, KRAS for anti-EGFR antibodies in Colorectal Cancer, and BCR-ABL1 for Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia , 2010 .

[17]  David Veenstra,et al.  How comparative effectiveness research can help advance 'personalized medicine' in cancer treatment. , 2011, Health affairs.

[18]  Laura A. Levit,et al.  Finding what works in health care : standards for systematic reviews , 2011 .

[19]  Funda Meric-Bernstam,et al.  Building a personalized medicine infrastructure at a major cancer center. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  Karen C. Lee,et al.  Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women. , 2015, American family physician.

[21]  K. Nicolaides,et al.  Analysis of cell‐free DNA in maternal blood in screening for fetal aneuploidies: updated meta‐analysis , 2015, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[22]  Elizabeth M. Webber,et al.  Fecal DNA Testing in Screening for Colorectal Cancer in Average-Risk Adults , 2012 .

[23]  Diana Miglioretti,et al.  Cell-free DNA Analysis for Noninvasive Examination of Trisomy. , 2015, The New England journal of medicine.

[24]  J. Saffitz.  Genomic pathology: a disruptive innovation. , 2012, Personalized medicine.

[25]  Rita Barallon,et al.  A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. , 2013, The New England journal of medicine.

[26]  Blue Cross Blue Shield Asssociation.  Gene expression profiling in women with lymph node-negative breast cancer to select adjuvant chemotherapy. , 2014, Technology Evaluation Center Assessment Program. Executive summary.

[27]  Laura A. Levit,et al.  COMMITTEE ON STANDARDS FOR SYSTEMATIC REVIEWS OF COMPARATIVE EFFECTIVENESS RESEARCH , 2011 .

[28]  M. Watson,et al.  Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics , 2016, Genetics in Medicine.

[29]  M. Pirmohamed,et al.  A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions , 2016, PharmacoEconomics.

[30]  L. V. van't Veer,et al.  70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. , 2016, The New England journal of medicine.

[31]  Y. Gao,et al.  Non‐invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146 958 pregnancies , 2015, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[32]  T. Ratko.  Gene expression analysis for prostate cancer management. , 2015, Technology Evaluation Center Assessment Program. Executive summary.

[33]  Geoffrey S Ginsburg,et al.  Comparative effectiveness research, genomics-enabled personalized medicine, and rapid learning health care: a common bond. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  R. Califf,et al.  A pharmacogenetic versus a clinical algorithm for warfarin dosing. , 2013, The New England journal of medicine.

[35]  Blue Cross Blue Shield Asssociation.  Fecal DNA analysis for colorectal cancer screening. , 2014, Technology Evaluation Center Assessment Program. Executive summary.

[36]  F. Frueh,et al.  Evidence of Clinical Utility: An Unmet Need in Molecular Diagnostics for Patients with Cancer , 2014, Clinical Cancer Research.

[37]  S. Langlois,et al.  Current status in non-invasive prenatal detection of Down syndrome, trisomy 18, and trisomy 13 using cell-free DNA in maternal plasma. , 2013, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[38]  Aniwaa Owusu Obeng,et al.  Clinical pharmacogenetics implementation: Approaches, successes, and challenges , 2014, American journal of medical genetics. Part C, Seminars in medical genetics.

[39]  Kathryn A Phillips,et al.  Genomic sequencing: assessing the health care system, policy, and big-data implications. , 2014, Health affairs.

[40]  V. Moyer.  Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. , 2014, Annals of internal medicine.

[41]  Rahber Thariani,et al.  Prioritization in Comparative Effectiveness Research: The CANCERGEN Experience , 2012, Medical care.

[42]  H. Hakonarson,et al.  Genetic Testing for Developmental Disabilities, Intellectual Disability, and Autism Spectrum Disorder , 2015 .

[43]  A. Wu,et al.  Methods for Developing Patient-Reported Outcome-Based Performance Measures (PRO-PMs). , 2015, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[44]  Maarten Joost IJzerman,et al.  Implementation of comparative effectiveness research in personalized medicine applications in oncology: current and future perspectives , 2015 .

[45]  Ku-Lang Chang,et al.  Pharmacogenetics: Using Genetic Information to Guide Drug Therapy. , 2015, American family physician.

[46]  L. Falzon,et al.  Gene Expression Profiling for Predicting Outcomes in Stage II Colon Cancer , 2012 .

[47]  Rongwei Fu,et al.  Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation , 2014, Annals of Internal Medicine.

[48]  BlueCross BlueShield.  Special report: exome sequencing for clinical diagnosis of patients with suspected genetic disorders. , 2013, Technology Evaluation Center Assessment Program. Executive summary.

[49]  S. Haga,et al.  Comparative effectiveness research and demonstrating clinical utility for molecular diagnostic tests. , 2015, Clinical chemistry.

[50]  G. Palomaki,et al.  PCA3 Testing for the Diagnosis and Management of Prostate Cancer , 2013 .

[51]  T. Marteau,et al.  Effects of communicating DNA-based disease risk estimates on risk-reducing behaviours. , 2010, The Cochrane database of systematic reviews.

[52]  R. Gliklich,et al.  RiGOR: a prospective observational study comparing the effectiveness of treatment strategies for open-angle glaucoma. , 2016, Journal of comparative effectiveness research.

[53]  Kathryn A Phillips,et al.  Challenges of coverage policy development for next-generation tumor sequencing panels: experts and payers weigh in. , 2015, Journal of the National Comprehensive Cancer Network : JNCCN.

[54]  G. Omenn,et al.  Evolution of Translational Omics: Lessons Learned and the Path Forward , 2013 .

[55]  Marc S. Williams,et al.  ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing , 2013, Genetics in Medicine.

[56]  M. Ashok,et al.  Technology Assessment of Molecular Pathology Testing for the Estimation of Prognosis for Common Cancers , 2014 .

[57]  J. Crowley,et al.  Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes. , 2013, Contemporary clinical trials.

[58]  Muin J Khoury,et al.  Comparative effectiveness research and genomic medicine: An evolving partnership for 21st century medicine , 2009, Genetics in Medicine.