Research Article| Volume 19, ISSUE 4, P815-831, December 1999

The Impact of Molecular Diagnostic Tests on Patient Outcomes

  • Jeffrey S. Ross
    Address reprint requests to: Jeffrey S. Ross, MD, A-81 Department of Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208
    From the Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York
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      This paper is only available as a PDF. To read, Please Download here.
      In order for the benefits of molecular pathology to outweigh its inherent costs, the procedures must be integrated into the assessment of the total disease management to realize the true impact of their financial and clinical outcomes. Major financial and patient outcome benefits are achievable from molecular testing by the ability to reduce the use of less-sensitive and less-specific tests and cause a decrease the use of unnecessary diagnostic procedures and ineffective therapies. In this review, the financial and patient care determinants of outcomes for molecular-based testing of disease predisposition, screening, early detection, and directed therapy are presented.
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        • Akao T.
        • Kahei Y.
        • Wu X-X.
        • et al.
        Semi-quantitative analysis of telomerase activity of exfoliated cells in urine of patients with urothelial cancers.
        Urol Oncol. 1997; 3: 118-124
        • American Society of Human Genetics
        Statement of the American Society of Human Genetics on cystic fibrosis carrier screening.
        Am J Hum Genet. 1992; 51: 1443-1444
        • Apple S.K.
        • Hecht J.R.
        • Novak J.M.
        • et al.
        Polymerase chain reaction-based mutation detection of pancreatic adenocarcinoma in routine cytology smears.
        Am J Clin Pathol. 1996; 105: 321-326
        • Bombard A.T.
        • Fields A.L.
        • Aufox S.
        • Ben-Yishay M.
        The genetics of ovarian cancer: An assessment of current screening protocols and recommendations for counseling families at risk.
        Clin Obstet Gynecol. 1996; 39: 860-872
        • Bradley S.P.
        • Reed S.L.
        • Catanzaro A.
        Clinical efficacy of the Amplified Mycobacterium Tuberculosis Direct Test for the diagnosis of pulmonary tuberculosis.
        Am Rev Resp Crit Care Med. 1996; 153: 1606-1610
        • Brisco M.J.
        • Condon J.
        • Hughes E.
        • et al.
        Outcome prediction in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of induction.
        Lancet. 1994; 343: 196-200
        • Burke W.
        • Daly M.
        • Garber J.
        • et al.
        Recommendations for follow-up care of individuals with an inherited predisposition for cancer. II. BRCA1 and BRCA2.
        JAMA. 1997; 277: 997-1003
        • Centers for Disease Control and Prevention
        Nucleic acid amplification tests for tuberculosis.
        MMWR Morb Mortal Wkly Rep. 1996; 45: 950-951
        • Centers for Disease Control and Prevention
        Report of the NIH panel to define principles of therapy of HIV infection and guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents.
        MMWR. 1998; 47: 9
        • Claus E.B.
        • Schildkraut J.M.
        • Thompson W.D.
        • Risch N.J.
        The genetic attributable risk of breast and ovarian cancer.
        Cancer. 1996; 77: 2318-2324
        • Cutting G.R.
        • Kasch L.M.
        • Rosenstein B.J.
        • et al.
        Two patients with cystic fibrosis, nonsense mutations in each cystic fibrosis gene, and mild pulmonary disease.
        N Engl J Med. 1990; 323: 1685-1689
        • Dailey P.J.
        • Hayden D.
        Viral load assays: Methodologies, variables, and interpretation.
        in: Cohen P.T. Sande M.A. Volberding P.A. The AIDS Knowledge Base. ed 3. Lippincott-Raven, Philadelphia1999
        • Dibenedetto S.P.
        • Lo Nigro L.
        • Pine Mayer S.
        • et al.
        Detectable molecular residual disease at the beginning of maintenance therapy indicates poor outcome in children with T-cell acute lymphoblastic leukemia.
        Blood. 1997; 90: 1226-1232
        • Feder J.N.
        • Gnirke A.
        • Thomas W.
        • et al.
        A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis.
        Nat Genet. 1996; 13: 399-408
        • Ferenczy A.
        • Franco E.
        • Arseneau J.
        • et al.
        Diagnostic performance of hybrid capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study.
        Am J Obstet Gynecol. 1996; 175: 651-656
        • Ferreira-Gonzalez A.
        • Garrett C.G.
        Pitfalls in establishing a molecular diagnostic laboratory.
        Hum Pathol. 1996; 27: 437-440
        • Ferris D.G.
        • Wright Jr, T.C.
        • Litaker M.S.
        • et al.
        Triage for women with ASCUS and LSIL on Pap smear reports: Management by repeat Pap smear, HPV DNA testing, or colposcopy?.
        J Fam Pract. 1998; 46: 125-134
        • Fessel W.J.
        Human immunodeficiency virus (HIV) RNA in plasma as the preferred target for therapy in patients with HIV infection: A critique.
        Clin Infect Dis. 1997; 24: 116-122
        • Fisher B.
        • Constantino J.P.
        • Wickerham D.L.
        • et al.
        Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project.
        J Natl Cancer Inst. 1990; 86: 1371-1388
        • Ford D.
        • Easton D.F.
        • Bishop D.T.
        • et al.
        Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers.
        Lancet. 1994; 343: 692-695
        • Ford D.
        • Easton D.F.
        • Stratton M.
        • et al.
        Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families.
        Am J Hum Genet. 1998; 62: 676-689
        • Grody W.W.
        • Dunkel-Schetter C.
        • Tatzugawa Z.H.
        • et al.
        PCR-based screening for cystic fibrosis carrier mutations in an ethnically diverse pregnant population.
        Am J Hum-Genet. 1997; 60: 935-947
        • Hodinka R.L.
        The clinical utility of viral quantitation using molecular methods.
        Clin Diagn Virol. 1998; 10: 25-47
        • Howell M.R.
        • Quinn T.C.
        • Brathwaite W.
        • Gaydos C.A.
        Screening women for Chlamydia trachomatis in family planning clinics: The cost-effectiveness of DNA amplification assays.
        Sex Transm Dis. 1998; 25: 108-117
        • Kerem B-S.
        • Rommens J.M.
        • Buchanan J.A.
        • et al.
        Identification of the cystic fibrosis gene: Genetic analysis.
        Science. 1989; 245: 1073-1080
        • Koenig M.
        • Hoffman E.P.
        • Bertelson C.J.
        • et al.
        Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals.
        Cell. 1987; 50: 509-517
        • Lerman C.
        • Narod S.
        • Schulman K.
        • et al.
        BRCA1 testing in families with hereditary breast-ovarian cancer: A prospective study of patient decision making and outcomes.
        JAMA. 1996; 275: 1885-1892
        • Mulligan L.M.
        • Kwok J.B.J.
        • Healy C.S.
        • et al.
        Germ-line mutations of the RET protooncogene in multiple endocrine neoplasia type 2A.
        Nature. 1993; 363: 458-460
        • Naod S.A.
        • Risch H.
        • Moslehi R.
        • et al.
        Oral contraceptives and the risk of hereditary ovarian cancer.
        N Engl J Med. 1998; 339: 424-428
        • NIH Consensus Development Panel on Ovarian Cancer
        Ovarian cancer screening, treatment and follow-up.
        JAMA. 1995; 273: 491-497
        • Okazaki K.
        • Morita M.
        • Yamamoto Y.
        Gene rearrangements, Helicobactor pylori, and gastric MALT lymphoma.
        Lancet. 1994; 343: 1636
        • Paavonen J.
        • Puolakkainen P.
        • Paukku M.
        • Sintonen H.
        Cost-benefit analysis of first-void urine Chlamydia trachomatis screening program.
        Obstet Gynecol. 1998; 92: 292-298
        • Richart R.M.
        • Masood S.
        • Syrjanen K.J.
        • et al.
        Human papillomavirus. IAC task force summary.
        Acta Cytol. 1998; 42: 50-58
        • Roberts M.
        • Estrov Z.
        • Kitchingman R.
        • et al.
        The significance of residual disease in childhood acute lymphoblastic leukemia as detected by polymerase chain reaction amplification of antigen-receptor gene sequences.
        Leuk Lymphoma. 1996; 20: 181-197
        • Rommens J.M.
        • Ianuzzi M.C.
        • Kerem B-S.
        • et al.
        Identification of the cystic fibrosis gene: Chromosome walking and jumping.
        Science. 1989; 245: 1059-1065
        • Rose D.N.
        • Sacks H.S.
        Cost-effectiveness of cytomegalovirus disease prevention in patients with AIDS: Oral ganciclovir and CMV polymerase chain reaction testing.
        AIDS. 1997; 11: 883-887
        • Rosin M.P.
        • Anwar W.A.
        • Ward A.J.
        Inflammation, chromosomal instability, and cancer: The schistosomiasis model.
        Cancer Res. 1994; 54: 1929s-1933s
        • Ross J.S.
        Molecular pathology and managed care: Challenges and opportunities.
        Diagn Mol Pathol. 1998; 10: 1-3
        • Ross J.S.
        • Fletcher J.A.
        The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy.
        Oncologist. 1998; 3: 237-252
        • Sader H.S.
        • Hollis R.J.
        • Pfaller M.A.
        The use of molecular techniques in the epidemiology and control of infectious diseases.
        Clin Lab Med. 1995; 15: 407-431
        • Sherman M.E.
        • Schiffman M.H.
        • Strickler H.
        • Hildesheim A.
        Prospects for a prophylactic HPV vaccine: Rationale and future implications for cervical cancer screening.
        Diagn Cytopathol. 1998; 18: 5-9
        • Sidransky D.
        Nucleic acid-based methods for the detection of cancer.
        Science. 1997; 278: 1054-1059
        • Solomon D.
        • Frable W.J.
        • Voojis G.P.
        • et al.
        ASCUS and AGUS criteria: IAC task force summary.
        Acta Cytol. 1998; 42: 16-24
        • Statement of the American Society of Clinical Oncology
        Genetic testing for cancer susceptibility.
        J Clin Oncol. 1996; 14: 1730-1736
        • Stoler M.H.
        A brief synopsis of the role of human papilloma virus in cervical carcinogenesis.
        Am J Obstet Gynecol. 1996; 175: 1091-1098
        • van Ballegooijen M.
        • van den Akker-van Marie M.E.
        • Warmerdam P.G.
        • et al.
        Present evidence on the value of HPV testing for cervical cancer screening: A model-based exploration of the cost-effectiveness.
        Br J Cancer. 1997; 76: 651-657
        • van der Riet A.A.
        • van Hout V.A.
        • Rutten F.F.
        Cost effectiveness of DNA diagnosis for four monogenic diseases.
        J Med Genet. 1997; 34: 741-745
        • Vasen H.F.
        • van Ballegooijen M.
        • Buskens E.
        • et al.
        A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis colorectal carcinoma gene carriers.
        Cancer. 1998; 82: 1632-1637
        • Verhoog L.C.
        • Brekelmans C.T.M.
        • Seynaeve C.
        • et al.
        Survival and tumor characteristics of breast cancer patients with germline mutations of BRCA1.
        Lancet. 1998; 351: 316-321
        • Wasserman R.
        • Galili N.
        • Ito Y.
        • et al.
        Residual disease at the end of induction therapy as a predictor of relapse during therapy of childhood B-lineage acute lymphoblastic leukemia.
        J Clin Oncol. 1992; 10: 1879-1888
        • Watson M.S.
        Current activities involving economic, regulatory, and practice issues in molecular genetic testing.
        Diagn Mol Pathol. 1995; 4: 233-234
        • Weber S.
        • Pfaller M.A.
        • Herwaldt L.A.
        Role of molecular epidemiology in infection control.
        Infect Dis Clin North Am. 1997; 25: 858-870
        • Workshop on Population Screening for the Cystic Fibrosis Gene
        Statement from the National Institutes of Health Workshop on Population Screening for the Cystic Fibrosis Gene.
        N Engl J Med. 1990; 323: 70-71
        • Xue F.
        • Yu H.
        • Maurer L.H.
        • et al.
        Germline RET mutations in MEN2A and FMTC and their detection by simple DNA diagnostic tests.
        Hum Mol Genet. 1994; 3: 635-638
        • zur Hausen H.
        Viruses in human tumors-reminiscences and perspectives.
        Adv Cancer Res. 1996; 68: 1-22