Skip to main content
Top
Published in: Trials 1/2014

Open Access 01-12-2014 | Study protocol

The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine

Authors: Jason L Vassy, Denise M Lautenbach, Heather M McLaughlin, Sek Won Kong, Kurt D Christensen, Joel Krier, Isaac S Kohane, Lindsay Z Feuerman, Jennifer Blumenthal-Barby, J Scott Roberts, Lisa Soleymani Lehmann, Carolyn Y Ho, Peter A Ubel, Calum A MacRae, Christine E Seidman, Michael F Murray, Amy L McGuire, Heidi L Rehm, Robert C Green, for the MedSeq Project

Published in: Trials | Issue 1/2014

Login to get access

Abstract

Background

Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care.

Methods/Design

This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients’ genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results.

Discussion

The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies.

Trial registration

ClinicalTrials.gov identifierNCT01736566
Appendix
Available only for authorised users
Literature
2.
go back to reference Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, Serpe JM, Dasu T, Tschannen MR, Veith RL, Basehore MJ, Broeckel U, Tomita-Mitchell A, Arca MJ, Casper JT, Margolis DA, Bick DP, Hessner MJ, Routes JM, Verbsky JW, Jacob HJ, Dimmock DP: Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011, 13: 255-262. 10.1097/GIM.0b013e3182088158.CrossRefPubMed Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, Serpe JM, Dasu T, Tschannen MR, Veith RL, Basehore MJ, Broeckel U, Tomita-Mitchell A, Arca MJ, Casper JT, Margolis DA, Bick DP, Hessner MJ, Routes JM, Verbsky JW, Jacob HJ, Dimmock DP: Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011, 13: 255-262. 10.1097/GIM.0b013e3182088158.CrossRefPubMed
3.
go back to reference Knies K, Schuster B, Ameziane N, Rooimans M, Bettecken T, de Winter J, Schindler D: Genotyping of Fanconi anemia patients by whole exome sequencing: advantages and challenges. PLoS One. 2012, 7: e52648-10.1371/journal.pone.0052648.CrossRefPubMedPubMedCentral Knies K, Schuster B, Ameziane N, Rooimans M, Bettecken T, de Winter J, Schindler D: Genotyping of Fanconi anemia patients by whole exome sequencing: advantages and challenges. PLoS One. 2012, 7: e52648-10.1371/journal.pone.0052648.CrossRefPubMedPubMedCentral
4.
go back to reference Bainbridge MN, Wiszniewski W, Murdock DR, Friedman J, Gonzaga-Jauregui C, Newsham I, Reid JG, Fink JK, Morgan MB, Gingras MC, Muzny DM, Hoang LD, Yousaf S, Lupski JR, Gibbs RA: Whole-genome sequencing for optimized patient management. Sci Transl Med. 2011, 3: 87re83-CrossRef Bainbridge MN, Wiszniewski W, Murdock DR, Friedman J, Gonzaga-Jauregui C, Newsham I, Reid JG, Fink JK, Morgan MB, Gingras MC, Muzny DM, Hoang LD, Yousaf S, Lupski JR, Gibbs RA: Whole-genome sequencing for optimized patient management. Sci Transl Med. 2011, 3: 87re83-CrossRef
5.
go back to reference Egan JB, Shi CX, Tembe W, Christoforides A, Kurdoglu A, Sinari S, Middha S, Asmann Y, Schmidt J, Braggio E, Keats JJ, Fonseca R, Bergsagel PL, Craig DW, Carpten JD, Stewart AK: Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood. 2012, 120: 1060-1066. 10.1182/blood-2012-01-405977.CrossRefPubMedPubMedCentral Egan JB, Shi CX, Tembe W, Christoforides A, Kurdoglu A, Sinari S, Middha S, Asmann Y, Schmidt J, Braggio E, Keats JJ, Fonseca R, Bergsagel PL, Craig DW, Carpten JD, Stewart AK: Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood. 2012, 120: 1060-1066. 10.1182/blood-2012-01-405977.CrossRefPubMedPubMedCentral
6.
go back to reference Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, Humphray S, Saffrey P, Kingsbury Z, Weir JC, Betley J, Grocock RJ, Margulies EH, Farrow EG, Artman M, Safina NP, Petrikin JE, Hall KP, Kingsmore SF: Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med. 2012, 4: 154ra135-CrossRefPubMedPubMedCentral Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, Humphray S, Saffrey P, Kingsbury Z, Weir JC, Betley J, Grocock RJ, Margulies EH, Farrow EG, Artman M, Safina NP, Petrikin JE, Hall KP, Kingsmore SF: Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med. 2012, 4: 154ra135-CrossRefPubMedPubMedCentral
7.
go back to reference Talkowski ME, Ordulu Z, Pillalamarri V, Benson CB, Blumenthal I, Connolly S, Hanscom C, Hussain N, Pereira S, Picker J, Rosenfeld JA, Shaffer LG, Wilkins-Haug LE, Gusella JF, Morton CC: Clinical diagnosis by whole-genome sequencing of a prenatal sample. N Engl J Med. 2012, 367: 2226-2232. 10.1056/NEJMoa1208594.CrossRefPubMedPubMedCentral Talkowski ME, Ordulu Z, Pillalamarri V, Benson CB, Blumenthal I, Connolly S, Hanscom C, Hussain N, Pereira S, Picker J, Rosenfeld JA, Shaffer LG, Wilkins-Haug LE, Gusella JF, Morton CC: Clinical diagnosis by whole-genome sequencing of a prenatal sample. N Engl J Med. 2012, 367: 2226-2232. 10.1056/NEJMoa1208594.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Green RC, Rehm HL, Kohane IS: Clinical genome sequencing. Genomic and Personalized Medicine. Vol. 1. 2013, Waltham, PA: Academic Press, 102-122. 2CrossRef Green RC, Rehm HL, Kohane IS: Clinical genome sequencing. Genomic and Personalized Medicine. Vol. 1. 2013, Waltham, PA: Academic Press, 102-122. 2CrossRef
10.
go back to reference Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM: Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013, 369: 1502-1511. 10.1056/NEJMoa1306555.CrossRefPubMedPubMedCentral Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM: Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013, 369: 1502-1511. 10.1056/NEJMoa1306555.CrossRefPubMedPubMedCentral
12.
go back to reference Goldberger JJ, Buxton AE: Personalized medicine vs guideline-based medicine. JAMA. 2013, 309: 2559-2560. 10.1001/jama.2013.6629.CrossRefPubMed Goldberger JJ, Buxton AE: Personalized medicine vs guideline-based medicine. JAMA. 2013, 309: 2559-2560. 10.1001/jama.2013.6629.CrossRefPubMed
13.
go back to reference McGuire AL, Diaz CM, Wang T, Hilsenbeck SG: Social networkers’ attitudes toward direct-to-consumer personal genome testing. Am J Bioeth. 2009, 9: 3-10.CrossRefPubMedPubMedCentral McGuire AL, Diaz CM, Wang T, Hilsenbeck SG: Social networkers’ attitudes toward direct-to-consumer personal genome testing. Am J Bioeth. 2009, 9: 3-10.CrossRefPubMedPubMedCentral
14.
go back to reference Kohane IS, Masys DR, Altman RB: The incidentalome: a threat to genomic medicine. JAMA. 2006, 296: 212-215. 10.1001/jama.296.2.212.CrossRefPubMed Kohane IS, Masys DR, Altman RB: The incidentalome: a threat to genomic medicine. JAMA. 2006, 296: 212-215. 10.1001/jama.296.2.212.CrossRefPubMed
15.
go back to reference McGuire AL, Burke W: An unwelcome side effect of direct-to-consumer personal genome testing: raiding the medical commons. JAMA. 2008, 300: 2669-2671. 10.1001/jama.2008.803.CrossRefPubMedPubMedCentral McGuire AL, Burke W: An unwelcome side effect of direct-to-consumer personal genome testing: raiding the medical commons. JAMA. 2008, 300: 2669-2671. 10.1001/jama.2008.803.CrossRefPubMedPubMedCentral
16.
go back to reference Green E, Guyer M: Charting a course for genomic medicine from base pairs to bedside. Nature. 2011, 470: 204-213. 10.1038/nature09764.CrossRefPubMed Green E, Guyer M: Charting a course for genomic medicine from base pairs to bedside. Nature. 2011, 470: 204-213. 10.1038/nature09764.CrossRefPubMed
17.
go back to reference Khoury MJ, McCabe LL, McCabe RB: Population screening in the age of genomic medicine. N Engl J Med. 2003, 348: 50-58. 10.1056/NEJMra013182.CrossRefPubMed Khoury MJ, McCabe LL, McCabe RB: Population screening in the age of genomic medicine. N Engl J Med. 2003, 348: 50-58. 10.1056/NEJMra013182.CrossRefPubMed
18.
go back to reference Khoury M, Berg A, Coates R, Evans J, Teutsch S, Bradley L: The evidence dilemma in genomic medicine. Health Aff. 2008, 27: 1600-1611. 10.1377/hlthaff.27.6.1600.CrossRef Khoury M, Berg A, Coates R, Evans J, Teutsch S, Bradley L: The evidence dilemma in genomic medicine. Health Aff. 2008, 27: 1600-1611. 10.1377/hlthaff.27.6.1600.CrossRef
19.
go back to reference Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N: Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013, 368: 1199-1209. 10.1056/NEJMoa1213261.CrossRefPubMed Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N: Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013, 368: 1199-1209. 10.1056/NEJMoa1213261.CrossRefPubMed
20.
go back to reference Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA: Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med. 2010, 362: 1181-1191. 10.1056/NEJMoa0908094.CrossRefPubMedPubMedCentral Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA: Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med. 2010, 362: 1181-1191. 10.1056/NEJMoa0908094.CrossRefPubMedPubMedCentral
21.
go back to reference Maxmen A: Exome sequencing deciphers rare diseases. Cell. 2011, 144: 635-637. 10.1016/j.cell.2011.02.033.CrossRefPubMed Maxmen A: Exome sequencing deciphers rare diseases. Cell. 2011, 144: 635-637. 10.1016/j.cell.2011.02.033.CrossRefPubMed
22.
go back to reference Quaynor SD, Stradtman EW, Kim HG, Shen Y, Chorich LP, Schreihofer DA, Layman LC: Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. N Engl J Med. 2013, 369: 164-171. 10.1056/NEJMoa1303611.CrossRefPubMed Quaynor SD, Stradtman EW, Kim HG, Shen Y, Chorich LP, Schreihofer DA, Layman LC: Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. N Engl J Med. 2013, 369: 164-171. 10.1056/NEJMoa1303611.CrossRefPubMed
23.
go back to reference Koser CU, Bryant JM, Becq J, Torok ME, Ellington MJ, Marti-Renom MA, Carmichael AJ, Parkhill J, Smith GP, Peacock SJ: Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. N Engl J Med. 2013, 369: 290-292. 10.1056/NEJMc1215305.CrossRefPubMed Koser CU, Bryant JM, Becq J, Torok ME, Ellington MJ, Marti-Renom MA, Carmichael AJ, Parkhill J, Smith GP, Peacock SJ: Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. N Engl J Med. 2013, 369: 290-292. 10.1056/NEJMc1215305.CrossRefPubMed
24.
go back to reference Köser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM, Ogilvy-Stuart AL, Hsu LY, Chewapreecha C, Croucher NJ, Harris SR, Sanders M, Enright MC, Dougan G, Bentley SD, Parkhill J, Fraser LJ, Betley JR, Schulz-Trieglaff OB, Smith GP, Peacock SJ: Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med. 2012, 366: 2267-2275. 10.1056/NEJMoa1109910.CrossRefPubMedPubMedCentral Köser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM, Ogilvy-Stuart AL, Hsu LY, Chewapreecha C, Croucher NJ, Harris SR, Sanders M, Enright MC, Dougan G, Bentley SD, Parkhill J, Fraser LJ, Betley JR, Schulz-Trieglaff OB, Smith GP, Peacock SJ: Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med. 2012, 366: 2267-2275. 10.1056/NEJMoa1109910.CrossRefPubMedPubMedCentral
25.
go back to reference Loman NJ, Constantinidou C, Christner M, Rohde H, Chan JZ, Quick J, Weir JC, Quince C, Smith GP, Betley JR, Aepfelbacher M, Pallen MJ: A culture-independent sequence-based metagenomics approach to the investigation of an outbreak of shiga-toxigenic escherichia coli O104:H4. JAMA. 2013, 309: 1502-1510. 10.1001/jama.2013.3231.CrossRefPubMed Loman NJ, Constantinidou C, Christner M, Rohde H, Chan JZ, Quick J, Weir JC, Quince C, Smith GP, Betley JR, Aepfelbacher M, Pallen MJ: A culture-independent sequence-based metagenomics approach to the investigation of an outbreak of shiga-toxigenic escherichia coli O104:H4. JAMA. 2013, 309: 1502-1510. 10.1001/jama.2013.3231.CrossRefPubMed
26.
go back to reference Crotti L, Tester DJ, White WM, Bartos DC, Insolia R, Besana A, Kunic JD, Will ML, Velasco EJ, Bair JJ, Ghidoni A, Cetin I, Van Dyke DL, Wick MJ, Brost B, Delisle BP, Facchinetti F, George AL, Schwartz PJ, Ackerman MJ: Long QT syndrome-associated mutations in intrauterine fetal death. JAMA. 2013, 309: 1473-1482. 10.1001/jama.2013.3219.CrossRefPubMed Crotti L, Tester DJ, White WM, Bartos DC, Insolia R, Besana A, Kunic JD, Will ML, Velasco EJ, Bair JJ, Ghidoni A, Cetin I, Van Dyke DL, Wick MJ, Brost B, Delisle BP, Facchinetti F, George AL, Schwartz PJ, Ackerman MJ: Long QT syndrome-associated mutations in intrauterine fetal death. JAMA. 2013, 309: 1473-1482. 10.1001/jama.2013.3219.CrossRefPubMed
27.
go back to reference Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG: ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013, 15: 565-574. 10.1038/gim.2013.73.CrossRefPubMedPubMedCentral Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG: ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013, 15: 565-574. 10.1038/gim.2013.73.CrossRefPubMedPubMedCentral
28.
go back to reference Dorschner MO, Amendola LM, Turner EH, Robertson PD, Shirts BH, Gallego CJ, Bennett RL, Jones KL, Tokita MJ, Bennett JT, Kim JH, Rosenthal EA, Kim DS, Tabor HK, Bamshad MJ, Motulsky AG, Scott CR, Pritchard CC, Walsh T, Burke W, Raskind WH, Byers P, Hisama FM, Nickerson DA, Jarvik GP, National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project: Actionable, pathogenic incidental findings in 1,000 participants’ exomes. Am J Hum Genet. 2013, 93: 631-640. 10.1016/j.ajhg.2013.08.006.CrossRefPubMedPubMedCentral Dorschner MO, Amendola LM, Turner EH, Robertson PD, Shirts BH, Gallego CJ, Bennett RL, Jones KL, Tokita MJ, Bennett JT, Kim JH, Rosenthal EA, Kim DS, Tabor HK, Bamshad MJ, Motulsky AG, Scott CR, Pritchard CC, Walsh T, Burke W, Raskind WH, Byers P, Hisama FM, Nickerson DA, Jarvik GP, National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project: Actionable, pathogenic incidental findings in 1,000 participants’ exomes. Am J Hum Genet. 2013, 93: 631-640. 10.1016/j.ajhg.2013.08.006.CrossRefPubMedPubMedCentral
30.
go back to reference Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370. 10.1111/j.1600-0447.1983.tb09716.x.CrossRefPubMed Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370. 10.1111/j.1600-0447.1983.tb09716.x.CrossRefPubMed
32.
go back to reference Nippert I, Harris HJ, Julian-Reynier C, Kristoffersson U, Ten Kate LP, Anionwu E, Benjamin C, Challen K, Schmidtke J, Nippert RP, Harris R: Confidence of primary care physicians in their ability to carry out basic medical genetic tasks-a European survey in five countries-Part 1. J Community Genet. 2011, 2: 1-11. 10.1007/s12687-010-0030-0.CrossRefPubMed Nippert I, Harris HJ, Julian-Reynier C, Kristoffersson U, Ten Kate LP, Anionwu E, Benjamin C, Challen K, Schmidtke J, Nippert RP, Harris R: Confidence of primary care physicians in their ability to carry out basic medical genetic tasks-a European survey in five countries-Part 1. J Community Genet. 2011, 2: 1-11. 10.1007/s12687-010-0030-0.CrossRefPubMed
33.
go back to reference Najafzadeh M, Lynd LD, Davis JC, Bryan S, Anis A, Marra M, Marra CA: Barriers to integrating personalized medicine into clinical practice: a best-worst scaling choice experiment. Genet Med. 2012, 14: 520-526. 10.1038/gim.2011.26.CrossRefPubMed Najafzadeh M, Lynd LD, Davis JC, Bryan S, Anis A, Marra M, Marra CA: Barriers to integrating personalized medicine into clinical practice: a best-worst scaling choice experiment. Genet Med. 2012, 14: 520-526. 10.1038/gim.2011.26.CrossRefPubMed
34.
go back to reference Selkirk CG, Weissman SM, Anderson A, Hulick PJ: Physicians’ preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genet Test Mol Biomarkers. 2013, 17: 219-225. 10.1089/gtmb.2012.0165.CrossRefPubMed Selkirk CG, Weissman SM, Anderson A, Hulick PJ: Physicians’ preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genet Test Mol Biomarkers. 2013, 17: 219-225. 10.1089/gtmb.2012.0165.CrossRefPubMed
35.
go back to reference Scheuner MT, Sieverding P, Shekelle PG: Delivery of genomic medicine for common chronic adult diseases: a systematic review. JAMA. 2008, 299: 1320-1334. 10.1001/jama.299.11.1320.CrossRefPubMed Scheuner MT, Sieverding P, Shekelle PG: Delivery of genomic medicine for common chronic adult diseases: a systematic review. JAMA. 2008, 299: 1320-1334. 10.1001/jama.299.11.1320.CrossRefPubMed
36.
go back to reference Korf BR, Ledbetter D, Murray MF: Report of the banbury summit meeting on the evolving role of the medical geneticist, February 12–14, 2006. Genet Med. 2008, 10: 502-507. 10.1097/GIM.0b013e31817701fe.CrossRefPubMed Korf BR, Ledbetter D, Murray MF: Report of the banbury summit meeting on the evolving role of the medical geneticist, February 12–14, 2006. Genet Med. 2008, 10: 502-507. 10.1097/GIM.0b013e31817701fe.CrossRefPubMed
37.
go back to reference Cooksey JA, Forte G, Benkendorf J, Blitzer MG: The state of the medical geneticist workforce: findings of the 2003 survey of American Board of Medical Genetics certified geneticists. Genet Med. 2005, 7: 439-443. 10.1097/01.GIM.0000172416.35285.9F.CrossRefPubMed Cooksey JA, Forte G, Benkendorf J, Blitzer MG: The state of the medical geneticist workforce: findings of the 2003 survey of American Board of Medical Genetics certified geneticists. Genet Med. 2005, 7: 439-443. 10.1097/01.GIM.0000172416.35285.9F.CrossRefPubMed
38.
go back to reference Association of American Medical Colleges Center for Workforce Studies: Recent Studies and Reports on Physician Shortages in the US. 2012, Washington, DC: Association of American Medical Colleges Center for Workforce Studies Association of American Medical Colleges Center for Workforce Studies: Recent Studies and Reports on Physician Shortages in the US. 2012, Washington, DC: Association of American Medical Colleges Center for Workforce Studies
39.
go back to reference Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG: Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009, 42: 377-381. 10.1016/j.jbi.2008.08.010.CrossRefPubMed Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG: Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009, 42: 377-381. 10.1016/j.jbi.2008.08.010.CrossRefPubMed
40.
go back to reference Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT: Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008, 456: 53-59. 10.1038/nature07517.CrossRefPubMedPubMedCentral Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT: Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008, 456: 53-59. 10.1038/nature07517.CrossRefPubMedPubMedCentral
41.
go back to reference Cooper DN, Stenson PD, Chuzhanova NA: The human gene mutation database (HGMD) and its exploitation in the study of mutational mechanisms. Curr Protoc Bioinformatics. 2006, Chapter 1: Unit 1 13-PubMed Cooper DN, Stenson PD, Chuzhanova NA: The human gene mutation database (HGMD) and its exploitation in the study of mutational mechanisms. Curr Protoc Bioinformatics. 2006, Chapter 1: Unit 1 13-PubMed
43.
go back to reference Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly M, Pugh T, Funke B, Rehm H, Lebo M: A systematic approach to assessing the clinical significance of genetic variants. Clin Genet. 2013, 84: 453-463. 10.1111/cge.12257.CrossRefPubMedPubMedCentral Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly M, Pugh T, Funke B, Rehm H, Lebo M: A systematic approach to assessing the clinical significance of genetic variants. Clin Genet. 2013, 84: 453-463. 10.1111/cge.12257.CrossRefPubMedPubMedCentral
44.
45.
go back to reference Aronson SJ, Clark EH, Babb LJ, Baxter S, Farwell LM, Funke BH, Hernandez AL, Joshi VA, Lyon E, Parthum AR, Russell FJ, Varugheese M, Venman TC, Rehm HL: The GeneInsight suite: a platform to support laboratory and provider use of DNA-based genetic testing. Hum Mutat. 2011, 32: 532-536. 10.1002/humu.21470.CrossRefPubMedPubMedCentral Aronson SJ, Clark EH, Babb LJ, Baxter S, Farwell LM, Funke BH, Hernandez AL, Joshi VA, Lyon E, Parthum AR, Russell FJ, Varugheese M, Venman TC, Rehm HL: The GeneInsight suite: a platform to support laboratory and provider use of DNA-based genetic testing. Hum Mutat. 2011, 32: 532-536. 10.1002/humu.21470.CrossRefPubMedPubMedCentral
46.
go back to reference Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P: Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008, 148: 295-309. 10.7326/0003-4819-148-4-200802190-00008.CrossRefPubMed Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P: Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008, 148: 295-309. 10.7326/0003-4819-148-4-200802190-00008.CrossRefPubMed
47.
go back to reference Schulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010, 152: 726-732. 10.7326/0003-4819-152-11-201006010-00232.CrossRefPubMed Schulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010, 152: 726-732. 10.7326/0003-4819-152-11-201006010-00232.CrossRefPubMed
48.
go back to reference Hall MA, Camacho F, Lawlor JS, Depuy V, Sugarman J, Weinfurt K: Measuring trust in medical researchers. Med Care. 2006, 44: 1048-1053. 10.1097/01.mlr.0000228023.37087.cb.CrossRefPubMed Hall MA, Camacho F, Lawlor JS, Depuy V, Sugarman J, Weinfurt K: Measuring trust in medical researchers. Med Care. 2006, 44: 1048-1053. 10.1097/01.mlr.0000228023.37087.cb.CrossRefPubMed
49.
go back to reference Joffe S, Cook EF, Cleary PD, Clark JW, Weeks JC: Quality of informed consent: a new measure of understanding among research subjects. J Natl Cancer Inst. 2001, 93: 139-147.CrossRefPubMed Joffe S, Cook EF, Cleary PD, Clark JW, Weeks JC: Quality of informed consent: a new measure of understanding among research subjects. J Natl Cancer Inst. 2001, 93: 139-147.CrossRefPubMed
50.
go back to reference O’Connor AM: Validation of a decisional conflict scale. Med Decis Making. 1995, 15: 25-30. 10.1177/0272989X9501500105.CrossRefPubMed O’Connor AM: Validation of a decisional conflict scale. Med Decis Making. 1995, 15: 25-30. 10.1177/0272989X9501500105.CrossRefPubMed
51.
go back to reference Kaphingst KA, McBride CM, Wade C, Alford SH, Reid R, Larson E, Baxevanis AD, Brody LC: Patients’ understanding of and responses to multiplex genetic susceptibility test results. Genet Med. 2012, 14: 681-687. 10.1038/gim.2012.22.CrossRefPubMedPubMedCentral Kaphingst KA, McBride CM, Wade C, Alford SH, Reid R, Larson E, Baxevanis AD, Brody LC: Patients’ understanding of and responses to multiplex genetic susceptibility test results. Genet Med. 2012, 14: 681-687. 10.1038/gim.2012.22.CrossRefPubMedPubMedCentral
52.
go back to reference Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG: Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012, 82: 408-415. 10.1111/j.1399-0004.2012.01909.x.CrossRefPubMedPubMedCentral Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG: Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012, 82: 408-415. 10.1111/j.1399-0004.2012.01909.x.CrossRefPubMedPubMedCentral
53.
go back to reference DeSalvo KB, Fan VS, McDonell MB, Fihn SD: Predicting mortality and healthcare utilization with a single question. Health Serv Res. 2005, 40: 1234-1246. 10.1111/j.1475-6773.2005.00404.x.CrossRefPubMedPubMedCentral DeSalvo KB, Fan VS, McDonell MB, Fihn SD: Predicting mortality and healthcare utilization with a single question. Health Serv Res. 2005, 40: 1234-1246. 10.1111/j.1475-6773.2005.00404.x.CrossRefPubMedPubMedCentral
54.
go back to reference Cella D, Hughes C, Peterman A, Chang CH, Peshkin BN, Schwartz MD, Wenzel L, Lemke A, Marcus AC, Lerman C: A brief assessment of concerns associated with genetic testing for cancer: the multidimensional impact of cancer risk assessment (MICRA) questionnaire. Health Psychol. 2002, 21: 564-572.CrossRefPubMed Cella D, Hughes C, Peterman A, Chang CH, Peshkin BN, Schwartz MD, Wenzel L, Lemke A, Marcus AC, Lerman C: A brief assessment of concerns associated with genetic testing for cancer: the multidimensional impact of cancer risk assessment (MICRA) questionnaire. Health Psychol. 2002, 21: 564-572.CrossRefPubMed
55.
go back to reference Carleton RN, Norton MA, Asmundson GJ: Fearing the unknown: a short version of the intolerance of uncertainty scale. J Anxiety Disord. 2007, 21: 105-117. 10.1016/j.janxdis.2006.03.014.CrossRefPubMed Carleton RN, Norton MA, Asmundson GJ: Fearing the unknown: a short version of the intolerance of uncertainty scale. J Anxiety Disord. 2007, 21: 105-117. 10.1016/j.janxdis.2006.03.014.CrossRefPubMed
56.
go back to reference Prochaska JO: Decision making in the transtheoretical model of behavior change. Med Decis Making. 2008, 28: 845-849. 10.1177/0272989X08327068.CrossRefPubMed Prochaska JO: Decision making in the transtheoretical model of behavior change. Med Decis Making. 2008, 28: 845-849. 10.1177/0272989X08327068.CrossRefPubMed
57.
go back to reference Zick CD, Mathews CJ, Roberts JS, Cook-Deegan R, Pokorski RJ, Green RC: Genetic testing for Alzheimer’s disease and its impact on insurance purchasing behavior. Health Aff (Millwood). 2005, 24: 483-490. 10.1377/hlthaff.24.2.483.CrossRef Zick CD, Mathews CJ, Roberts JS, Cook-Deegan R, Pokorski RJ, Green RC: Genetic testing for Alzheimer’s disease and its impact on insurance purchasing behavior. Health Aff (Millwood). 2005, 24: 483-490. 10.1377/hlthaff.24.2.483.CrossRef
58.
go back to reference Nelson D, Kreps G, Hesse B, Croyle R, Willis G, Arora N, Rimer B, Vish Viswanath K, Weinstein N, Alden S: The health information national trends survey (HINTS): development, design, and dissemination. J Health Commun. 2004, 9: 443-460. 10.1080/10810730490504233.CrossRefPubMed Nelson D, Kreps G, Hesse B, Croyle R, Willis G, Arora N, Rimer B, Vish Viswanath K, Weinstein N, Alden S: The health information national trends survey (HINTS): development, design, and dissemination. J Health Commun. 2004, 9: 443-460. 10.1080/10810730490504233.CrossRefPubMed
59.
go back to reference Degner LF, Sloan JA, Venkatesh P: The control preferences scale. Can J Nurs Res. 1997, 29: 21-43.PubMed Degner LF, Sloan JA, Venkatesh P: The control preferences scale. Can J Nurs Res. 1997, 29: 21-43.PubMed
61.
go back to reference Roter D, Larson S: The Roter interaction analysis system (RIAS): utility and flexibility for analysis of medical interactions. Patient Educ Couns. 2002, 46: 243-251. 10.1016/S0738-3991(02)00012-5.CrossRefPubMed Roter D, Larson S: The Roter interaction analysis system (RIAS): utility and flexibility for analysis of medical interactions. Patient Educ Couns. 2002, 46: 243-251. 10.1016/S0738-3991(02)00012-5.CrossRefPubMed
62.
go back to reference Brehaut JC, O’Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon E, Feldman-Stewart D: Validation of a decision regret scale. Med Decis Making. 2003, 23: 281-292. 10.1177/0272989X03256005.CrossRefPubMed Brehaut JC, O’Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon E, Feldman-Stewart D: Validation of a decision regret scale. Med Decis Making. 2003, 23: 281-292. 10.1177/0272989X03256005.CrossRefPubMed
Metadata
Title
The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine
Authors
Jason L Vassy
Denise M Lautenbach
Heather M McLaughlin
Sek Won Kong
Kurt D Christensen
Joel Krier
Isaac S Kohane
Lindsay Z Feuerman
Jennifer Blumenthal-Barby
J Scott Roberts
Lisa Soleymani Lehmann
Carolyn Y Ho
Peter A Ubel
Calum A MacRae
Christine E Seidman
Michael F Murray
Amy L McGuire
Heidi L Rehm
Robert C Green
for the MedSeq Project
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Trials / Issue 1/2014
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-15-85

Other articles of this Issue 1/2014

Trials 1/2014 Go to the issue