Assessing value of innovative molecular diagnostic tests in the concept of predictive, preventive, and personalized medicine

EPMA Journal

Rostyslav V. Bubnov²  Ildar Akhmetov¹ 

[1]Strategic Market Intelligence Dep., Unicorn, Zhytomyr 10020, Ukraine

[2]Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Zabolotny Str., 154, Kyiv 03680, Ukraine

关键词: Economic models;    Health technology assessment;    Reimbursement;    Cost-effectiveness;    Companion diagnostics;    Strategy;    Value;    Market access;    Predictive Preventive Personalized Medicine;   

Others  :  1230678
DOI  :  10.1186/s13167-015-0041-3

 received in 2015-07-22, accepted in 2015-09-08,  发布年份 2015

【 摘 要 】

Molecular diagnostic tests drive the scientific and technological uplift in the field of predictive, preventive, and personalized medicine offering invaluable clinical and socioeconomic benefits to the key stakeholders. Although the results of diagnostic tests are immensely influential, molecular diagnostic tests (MDx) are still grudgingly reimbursed by payers and amount for less than 5 % of the overall healthcare costs. This paper aims at defining the value of molecular diagnostic test and outlining the most important components of “value” from miscellaneous assessment frameworks, which go beyond accuracy and feasibility and impact the clinical adoption, informing healthcare resource allocation decisions. The authors suggest that the industry should facilitate discussions with various stakeholders throughout the entire assessment process in order to arrive at a consensus about the depth of evidence required for positive marketing authorization or reimbursement decisions. In light of the evolving “value-based healthcare” delivery practices, it is also recommended to account for social and ethical parameters of value, since these are anticipated to become as critical for reimbursement decisions and test acceptance as economic and clinical criteria.

【 授权许可】

   
2015 Akhmetov and Bubnov.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Golubnitschaja O, Costigliola V. General report & recommendations in predictive, preventive and personalised medicine 2012: white paper of the European Association for Predictive, Preventive and Personalised Medicine. EPMA J. 2012; 3(1):14. BioMed Central Full Text
• [2]Grech G, Zhan X, Yoo BC, Bubnov R, Hagan S, Danesi R et al.. EPMA position paper in cancer: current overview and future perspectives. EPMA J. 2015; 6:9. BioMed Central Full Text
• [3]Chow IP, Bryant T, Swanson S, Schoeninger B. Dissecting the value of companion diagnostics. IMS Consulting Group. 2013. Accessed from http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Healthcare/IMS%20Consulting/Our%20Latest%20Thinking/Q1_2013_IMSCG_Market_Access_Conference_Dissecting_The_Value_of_CDx_07_Mar2013.pdf on May 18, 2015.
• [4]Carson J. Molecular methods rapidly gain ground in infectious disease diagnostics. Frost & Sullivan. 2014. Accessed from http://ww2.frost.com/news/press-releases/molecular-methodsrapidly-gain-ground-infectious-disease-diagnostics-says-frost-sullivan/ on May 17, 2015.
• [5]NCBI. GTR: Genetic Testing Registry. NCBI. 2015. Accessed from http://www.ncbi.nlm.nih.gov/gtr/ on May 29, 2015.
• [6]Di Ruffano F, Hyde L, McCaffery CJ, Bossuyt KJ, Patrick MM, Deeks JJ. Assessing the value of diagnostic tests: a framework for designing and evaluating trials. BMJ. 2012; 344: Article ID e686
• [7]Lord SJ, Irwig L, Simes RJ. When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test, and when do we need randomized trials? Ann Intern Med. 2006; 144(11):850-5.
• [8]Forsman RW. Why is the laboratory an afterthought for managed care organizations? Clin Chem. 1996; 42(5):813-6.
• [9]Hanson C, Plumhoff E. Test utilization and the clinical laboratory. Mayo Clinic. 2012. Accessed from http://www.mayomedicallaboratories.com/articles/communique/2012/05.html on May 23, 2015.
• [10]Coamey J. MDx and MDs: is a dose of knowledge the prescription for adoption? CAHG. 2010. Accessed from http://www.healthtech.com/uploadedFiles/Conferences/White_Papers/MMTC/CAHG_LandmarkPhysicianStudy.pdf on May 18, 2015.
• [11]Drucker E, Krapfenbauer K. Pitfalls and limitations in translation from biomarker discovery to clinical utility in predictive and personalised medicine. EPMA J. 2013; 4(1):7. BioMed Central Full Text
• [12]Zelin J, Garrett N, Saunders J, Warburton F, Anderson J, Moir K et al.. North East London Sexual Health Network Research Consortium. An evaluation of the performance of OraQuick® ADVANCE Rapid HIV-1/2 Test in a high-risk population attending genitourinary medicine clinics in East London, UK. Int J STD AIDS. 2008; 19(10):665-7.
• [13]Caragher TE, Fernandez BB, Jacobs FL, Barr LA. Evaluation of quantitative cardiac biomarker point-of-care testing in the emergency department. J Emerg Med. 2002; 22(1):1-7.
• [14]McCord J, Nowak RM, McCullough PA, Foreback C, Borzak S, Tokarski G et al.. Ninety-minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I. Circulation. 2001; 104(13):1483-8.
• [15]Jørgensen OD, Kronborg O, Fenge C. A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds. Gut. 2002; 50(1):29-32.
• [16]Forrest GN, Roghmann MC, Toombs LS, Johnson JK, Weekes E, Lincalis DP et al.. Peptide nucleic acid fluorescent in situ hybridization for hospital-acquired enterococcal bacteremia: delivering earlier effective antimicrobial therapy. Antimicrob Agents Chemother. 2008; 52(10):3558-63.
• [17]Veenstra DL. The cost-effectiveness of warfarin pharmacogenomics. J Thromb Haemost. 2007; 5(9):1974-5.
• [18]Carlson B. KRAS testing: optimizing cancer therapy. Biotechnol Healthc. 2009; 6(5):7-9.
• [19]Asad J, Jacobson AF, Estabrook A, Smith SR, Boolbol SK, Feldman SM et al.. Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer? Am J Surg. 2008; 196(4):527-9.
• [20]Rich PA, Shaefer CF, Parkin CG, Edelman S. Using a quantitative measure of diabetes risk in clinical practice to target and maximize diabetes prevention interventions. Clin Diab. 2013; 31(2):82-9.
• [21]Schneider KI, Schmidtke J. Patient compliance based on genetic medicine: a literature review. J Comm Genet. 2014; 5(1):31-48.
• [22]PMC. Personalized medicine by the numbers. [Infographic]. PMC. 2014. Accessed from http://www.personalizedmedicinecoalition.org/Userfiles/PMCCorporate/file/pmc_personalized_medicine_by_the_numbers.pdf on June 2, 2015.
• [23]Falconi A, Lopes G, Parker JL. Biomarkers and receptor targeted therapies reduce clinical trial risk in non-small-cell lung cancer. J Thorac Oncol. 2014; 9(2):163-9.
• [24]Fitzal F, Filipits M, Rudas M, Greil R, Dietze O, Samonigg H et al.. The genomic expression test EndoPredict is a prognostic tool for identifying risk of local recurrence in postmenopausal endocrine receptor-positive, her2neu-negative breast cancer patients randomised within the prospective ABCSG 8 trial. Br J Cancer. 2015; 112(8):1405-10.
• [25]Garau M, Towse A, Garrison L, Housman L, Ossa D. Can and should value based pricing be applied to molecular diagnostics? 2012. Accessed from https://www.ohe.org/publications/canand-should-value-based-pricing-be-applied-molecular-diagnostics on May 21, 2015.
• [26]Lepik KJ, Harrigan PR, Barrios R, Milan D, Yip B, Chan K, et al. The impact of interventions to improve HLA-B*5701 allele screening to reduce risk of abacavir hypersensitivity reaction. AIDS 2010 - XVIII International AIDS Conference: Abstract no.WEPE0144. Accessed from https://www.iasociety.org/Abstracts/A200735296.aspx on May 25, 2015.
• [27]Armour AA, Watkins CL. The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer. Eur Respir Rev. 2010; 19(117):186-96.
• [28]Spackman E, Rice S, Norman G, Suh DC, Eastwood A, Palmer S. Trastuzumab for the treatment of HER2-positive metastatic gastric cancer. Pharmacoeconomics. 2013; 31(3):185-94.
• [29]Porter ME. Value-based health care delivery. [Video] HBS. 2012. Accessed from https://www.youtube.com/watch?v=DRkhppxZzL0 on May 29, 2015.
• [30]Porter ME. Value-based health care delivery. [Slides] HBS. 2012. Accessed from http://www.hbs.edu/healthcare/Documents/2012%2003%2007%20SUT%20HCI%20presentation.pdf on May 29, 2015.
• [31]Cosgrove T. Value-based health care is inevitable and that’s good. Harvard Business Review. 2013. Accessed from https://hbr.org/2013/09/value-based-health-care-is-inevitable-and-thatsgood/on May 19, 2015.
• [32]Catawba Valley Medical Center. CHESS And Catawba Valley Medical Center (CVMC) partner to adapt value-based healthcare delivery model. Catawba Valley Medical Center. 2015. Accessed from https://catawbavalleymedical.org/chess-catawba-valley-medical-center-cvmc-partner-adapt-value-based-healthcare-delivery-model/ on May 17, 2015.
• [33]MHA Task Force on Future Health Insurance Markets. Health insurance exchanges and the road to value-based payment in Michigan. MHHA. 2014. Accessed from http://www.mha.org/documents/tf_fhim_final_report_061814.pdf on May 27, 2015.
• [34]Carlson B. A truer way to measure value of diagnostic tests. Biotechnol Healthc. 2012; 9(4):34-5.
• [35]Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Mak. 1991; 11(2):88-94.
• [36]Silverstein MD, Boland BJ. Conceptual framework for evaluating laboratory tests: case-finding in ambulatory patients. Clin Chem. 1994; 40(8):1621-7.
• [37]Mackenzie R, Dixon AK. Measuring the effects of imaging: an evaluative framework. Clin Radiol. 1995; 50(8):513-8.
• [38]Pearson SD, Knudsen AB, Scherer RW, Weissberg J, Gazelle GS. Assessing the comparative effectiveness of a diagnostic technology: CT colonography. Health Aff (Millwood). 2008; 27(6):1503-14.
• [39]Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM et al.. Third US Preventive Services Task Force. Current methods of the U.S. Preventive Services Task Force. Am J Prev Med. 2001; 20(3 Suppl):21-35.
• [40]Trikalinos TA, Siebert U, Lau J. Decision-analytic modeling to evaluate benefits and harms of medical tests: uses and limitations. Med Decis Mak. 2009; 29(5):E22-9.
• [41]Schünemann HJ, Oxman AD, Brozek J, Glasziou P, Jaeschke R, Vist GE et al.. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008; 336(7653):1106-10.
• [42]Hayes DF, Bast RC, Desch CE, Fritsche H, Kemeny NE, Jessup JM et al.. Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst. 1996; 88(20):1456-66.
• [43]Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. JNCI J National Cancer Institute. 2009; 101(21):1446-52.
• [44]National Academy of Sciences. Generating evidence for genomic diagnostic test development: workshop summary. Institute of Medicine (US) Roundtable on Translating Genomic-Based Research for Health. 2011. Accessed from http://www.ncbi.nlm.nih.gov/books/NBK4119/ on July 2, 2015.
• [45]Wald N, Cuckle H. Reporting the assessment of screening and diagnostic tests. Br J Obstet Gynaecol. 1989; 96(4):389-96.
• [46]Haddow JE, Palomaki GE. An introduction to assessing genomic screening and diagnostic tests. Nutr Today. 2011; 46(4):162-8.
• [47]Bossuyt PM, McCaffery K. Additional patient outcomes and pathways in evaluations of testing. Med Decis Making. 2009; 29(5):E30-8.
• [48]Lee DW, Neumann PJ, Rizzo JA. Understanding the medical and nonmedical value of diagnostic testing. Value Health. 2010; 13(2):310-4.
• [49]Kopits IM, Chen C, Roberts JS, Uhlmann W, Green RC. Willingness to pay for genetic testing for Alzheimer’s disease: a measure of personal utility. Genet Test Mol Biomarkers. 2011; 15(12):871-5.
• [50]Task Force on Community Preventive Services. The guide to community preventive services—what works to promote health? Oxford University Press. 2005. Accessed from http://www.thecommunityguide.org/library/book/Front-Matter.pdf on June 5, 2015.
• [51]Grosse SD, Wordsworth S, Payne K. Economic methods for valuing the outcomes of genetic testing: beyond cost-effectiveness analysis. Genet Med. 2008; 10(9):648-54.
• [52]The Deerfield Institute. The Deerfield Institute—EuropaBio report on regulatory and scientific advice for small and medium enterprises. 2015. Accessed from http://www.europabio.org/sites/default/files/report/deerfield_europabio_survey_regulatory_and_hta_advice_for_smes_-_march_2015.pdf on June 7, 2015.
• [53]Foster NL, Hackett JSM, White G, Chenevert S, Svarvar P, Bain L et al.. Justifying reimbursement for Alzheimer’s diagnostics and treatments: seeking alignment on evidence. Alzheimers Dement. 2014; 10(4):503-8.
• [54]Faulkner E, Annemans L, Garrison L, Helfand M, Holtorf AP, Hornberger J et al.. Challenges in the development and reimbursement of personalized medicine—payer and manufacturer perspectives and implications for health economics and outcomes research: a report of the ISPOR Personalized Medicine Special Interest Group. Value Health. 2012; 15(8):1162-71.
• [55]Paci D, Ibarreta D. Economic and cost-effectiveness considerations for pharmacogenetics tests: an integral part of translational research and innovation uptake in personalized medicine. Current Pharmacogenomics, Personalized Med. 2009; 7(4):284-96.
• [56]Gustavsen G, Phillips K, Pothier K. The reimbursement landscape for novel diagnostics: current limitations, real-world impact, and proposed solutions: health advances. 2010. Accessed from https://www.bio.org/sites/default/files/Health_Advances%26BIO_Novel_Diagnostics_Reimburs_20110103.pdf on June 9, 2015.
• [57]Pearson SD. Assessing the “value” of tests and treatments in the US health care system. [Video] Philip R. Lee Institute for Health Policy Studies. 2014. Accessed from https://www.youtube.com/watch?v=yFZ2oUUrovE on May 29, 2015.
• [58]Pearson SD. A framework for payer assessment of the value of new technologies: a US approach (seminar briefing). Office of Health Economics. 2015. Accessed from https://www.ohe.org/publications/framework-payer-assessment-value-new-technologies-us-approach on June 1, 2015.
• [59]Akhmetov IR, Ramaswamy R, Akhmetov IR, Thimmaraju P. Market access advancements and challenges in “drug-companion diagnostic test” co-development in Europe. J Pers Med. 2015; 5(2):213-28.
• [60]Sorenson C, Drummond M, Kanavos P. Ensuring value for money in health care. The role of health technology assessment in the European Union. European Observatory on Health Systems and Policies. 2008. Accessed from http://www.euro.who.int/__data/assets/pdf_file/0011/98291/E91271.pdf on June 7, 2015.
• [61]Busse R, Orvain J, Velasco M, Perleth M, Drummond M, Gürtner F, Jørgensen T, Jovell A et al.. Best practice in undertaking and reporting health technology assessments. Int J Technol Assess Health Care. 2002; 18(2):361-422.
• [62]Barrett C, Magee H, O’Toole D, Daly S, Jeffers M. Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false‐positive or falsenegative immunohistochemistry? J Clin Pathol. 2007; 60(6):690-3.
• [63]Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al.. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344(11):783-92.
• [64]Garfield S. Advancing access to personalized medicine: a comparative assessment of European reimbursement systems. PMC. 2011. Accessed from http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/pmc_bridgehead_issue_brief_european_reimbursement.pdf on May 23, 2015.
• [65]Wilson PM, LaBonte MJ, Lenz HJ. Molecular markers in the treatment of metastatic colorectal cancer. Cancer J. 2010; 16(3):262-72.
• [66]Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ et al.. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26(10):1626-34.
• [67]Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC et al.. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65.
• [68]Rojas M, Yao SY, Lin YZ. Controlling epidermal growth factor (EGF)-stimulated Ras activation in intact cells by a cell-permeable peptide mimicking phosphorylated EGF receptor. J Biol Chem. 1996; 271(44):27456-61.
• [69]Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B et al.. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. Clin Oncol. 2007; 25(13):1658-64.
• [70]Van Cutsem E, Nowacki M, Lang I et al.. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial. J Clin Oncol. 2007; 25 Suppl:18s-s.
• [71]Westwood M, van Asselt T, Ramaekers B, Whiting P, Joore M, Armstrong N et al.. KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2014; 18:62.
• [72]Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF et al.. American society of clinical oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009; 27(12):2091-6.
• [73]Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J et al.. PREDICT-1 study team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008; 358(6):568-79.
• [74]Ma JD, Lee KC, Kuo GM. HLA-B*5701 testing to predict abacavir hypersensitivity. PLoS Currents. 2010; 2: Article ID RRN1203
• [75]Hughes DA, Vilar FJ, Ward CC, Alfirevic A, Park BK, Pirmohamed M. Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics. 2004; 14(6):335-42.
• [76]Aberg JA, Kaplan JELH, Emmanual P, Anderson JR, Stone VE, Oleske JM. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2009; 49:651-81.
• [77]Towse A, Ossa D, Veenstra D, Carlson J, Garrison L. Understanding the economic value of molecular diagnostic tests: case studies and lessons learned. JPM. 2013; 3:288-305.
• [78]CardioDx. Corus CAD clinical validity. CardioDx. 2015. Accessed from http://www.cardiodx.com/research-and-clinical-data/corus-cad-development-and-data/clinical-validity/ on June 7, 2015.
• [79]CardioDx. Study finds the Corus® CAD gene expression blood test influenced primary care decision-making in the assessment of patients with suspected obstructive coronary artery disease. 2015. Accessed from http://www.cardiodx.com/media-and-events/press-releases/study-finds-the-corus-cad-gene-expression-blood-test-influenced-primary-care-decision-making-inthe-assessment-of-patients-with-suspected-obstructive-coronary-artery-disease/ on May 17, 2015.
• [80]Palmetto GBA. Approved gene testing (M00041, V8). Palmetto GBA. 2015. Accessed from http://www.palmettogba.com/palmetto/MolDX.nsf/DocsCat/MolDx%20Website~MolDx~Browse%20By%20Topic~Covered%20Tests~9BMLRK6738?open&navmenu=%7C%7C on May 28, 2015.
• [81]Malone B. The reimbursement outlook for molecular diagnostics—shifting policies, market demands trace uncertain path. American Association for Clinical Chemistry. 2015. Accessed from https://www.aacc.org/publications/cln/articles/2015/april/the-reimbursement-outlook-for-molecular-diagnostics on May 26, 2015.