Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies

References

• Morgan J, Wannemuehler KA, Marr KA, et al. Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol 2005;43(Suppl. 1):49–58.
   PubMed Web of Science ®Google Scholar
• Pagano L, Caira M, Candoni A, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006;91:1068–1075.
   PubMed Web of Science ®Google Scholar
• Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 2007;44:531–540.
   PubMed Web of Science ®Google Scholar
• Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infections in adult hematopoietic stem cell transplant recipients: analysis of a multicenter prospective antifungal therapy (PATH) alliance registry. Clin Infect Dis 2009;48:265–273.
   PubMed Web of Science ®Google Scholar
• Reichenberger F, Habicht J, Matt P, et al. Diagnostic yield of bronchoscopy in histologically proven invasive pulmonary aspergillosis. Bone Marrow Transplant 1999;24:1195–1199.
   PubMed Web of Science ®Google Scholar
• Jantunen E, Piilonen A, Volin L, et al. Diagnostic aspects of invasive Aspergillus infections in allogeneic BMT recipients. Bone Marrow Transplant 2000;25:867–871.
   PubMed Web of Science ®Google Scholar
• Wingard JR. Empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis 2004;39(Suppl. 4):38–43.
   PubMed Web of Science ®Google Scholar
• Martino R, Viscoli C. Empirical antifungal therapy in patients with neutropenic and persistent or recurrent fever of unknown origin. Br J Haematol 2006;132:138–154.
   PubMed Web of Science ®Google Scholar
• Ben-Ami R, Lewis RE, Kontoyiannis DP. Invasive mold infections in the setting of hematopoietic cell transplantation: current trends and new challenges. Curr Opin Infect Dis 2009;22:376–384.
   PubMed Web of Science ®Google Scholar
• Verweij PE, Stynen D, Rijs AJ, de Pauw BE, Hoogkamp-Korstanje JA, Meis JF. Sandwich enzyme-linked immunosorbent assay compared with pastorex latex agglutination test for diagnosing invasive aspergillosis in immunocompromised patients. J Clin Microbiol 1995;33:1912–1914.
   PubMed Web of Science ®Google Scholar
• Bretagne S, Costa J-M, Bart-Delabesse E, Dhedin N, Rieux C, Cordonnier C. Comparison of serum galactomannan antigen detection and competitive polymerase chain reaction for diagnosing invasive aspergillosis. Clin Infect Dis 1998;26:1407–1412.
   PubMed Web of Science ®Google Scholar
• Maertens J, Verhaegen J, Demuynck H, et al. Autopsy-controlled prospective evaluation of serial screening for circulating galactomannan by a sandwich enzyme-linked immunosorbent assay for hematological patients at-risk for invasive aspergillosis. J Clin Microbiol 1999;37:3223–3228.
   PubMed Web of Science ®Google Scholar
• Kami M, Fukui T, Ogawa S, et al. Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis. Clin Infect Dis 2001;33:1504–1512.
   PubMed Web of Science ®Google Scholar
• Sulahian A, Boutboul F, Ribaud P, Lebalc T, Lacroix C, Derouin F. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Cancer 2001;91:311–318.
   PubMed Web of Science ®Google Scholar
• Costa C, Costa J-M, Desterke C, Botterel F, Cordonnier C, Bretagne S. Real-time PCR coupled with automated DNA extraction and detection of galactomannan antigen in serum by enzyme-linked immunosorbent assay for diagnosis of invasive aspergillosis. J Clin Microbiol 2002;40:2224–2227.
   PubMed Web of Science ®Google Scholar
• Herbrecht R, Letscher-Bru V, Oprea C, et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol 2002;20:1898–1906.
   PubMed Web of Science ®Google Scholar
• Maertens J, Van Eldere J, Verhaegen J, Verbeken E, Verschakelen J, Boogaerts M. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis 2002;186:1297–1306.
   PubMed Web of Science ®Google Scholar
• Pinel C, Fricker-Hidalgo H, Lebeau B, et al. Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis. J Clin Microbiol 2003;41:2184–2186.
   PubMed Web of Science ®Google Scholar
• Buchheidt D, Hummel M, Schleiermacher D, et al. Prospective clinical evaluation of a LightCyclerTM-mediated polymerase chain reaction assay, a nested-PCR assay and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol 2004;125:196–202.
   PubMed Web of Science ®Google Scholar
• Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis 2004;190:641–649.
   PubMed Web of Science ®Google Scholar
• Rovira M, Jimenez M, Puig de la Bellacasa J, et al. Detection of Aspergillus galactomannan by enzyme immunoabsorbent assay in recipients of allogeneic hematopoietic stem cell transplantation: a prospective study. Transplantation 2004;77:1260–1264.
   PubMed Web of Science ®Google Scholar
• Einsele H, Hebart H, Roller G, et al. Detection and identification of fungal pathogens in blood by using probes. J Clin Microbiol 1997;35:1353–1360.
   PubMed Web of Science ®Google Scholar
• Skladny H, Buchheidt D, Baust C, et al. Specific detection of Aspergillus species in blood and bronchoalveolar lavage samples of immunocompromised patients by two-step PCR. J Clin Microbiol 1999;37:3865–3871.
   PubMed Web of Science ®Google Scholar
• Hebart H, Loffler J, Meisner C, et al. Early detection of Aspergillus infection after allogeneic stem cell transplantation by polymerase chain reaction screening. J Infect Dis 2000;181:1713–1719.
   PubMed Web of Science ®Google Scholar
• Williamson EC, Leeming JP, Palmer HM, Steward CG, Warnock D. Diagnosis of invasive aspergillosis in bone marrow transplant recipients by polymerase chain reaction. Br J Haematol 2000;108:132–139.
   PubMed Web of Science ®Google Scholar
• Buchheidt D, Baust C, Skladny H, et al. Detection of Aspergillus species in blood and bronchoalveolar lavage samples from immunocompromised patients by means of 2-step polymerase chain reaction: clinical results. Clin Infect Dis 2001;33:428–435.
   PubMed Web of Science ®Google Scholar
• Lass-Flörl C, Aigner J, Gunsilius E, et al. Screening for Aspergillus spp. using polymerase chain reaction of whole blood samples from patients with haematological malignancies. Br J Haematol 2001;113:180–184.
   PubMed Web of Science ®Google Scholar
• Kawazu M, Kanda Y, Nannya Y, et al. Prospective comparison of the diagnostic potential of real-time PCR, double-sandwich enzyme-linked immunosorbent assay for galactomannan and a (1→3)-β-D-glucan test in weekly screening for invasive aspergillosis in patients with hematological disorder. J Clin Microbiol 2004;42:2733–2741.
   PubMed Web of Science ®Google Scholar
• Jordanides NE, Allan EK, McLintock LA, et al. A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients. Bone Marrow Transplant 2005;35:389–395.
   PubMed Web of Science ®Google Scholar
• Florent M, Katsahian S, Vekhoff A, et al. Prospective evaluation of a polymerase chain reaction-ELISA targeted to Aspergillus fumigatus and Aspergillus flavus for the early diagnosis of invasive aspergillosis in patients with hematological malignancies. J Infect Dis 2006;193:741–747.
   PubMed Web of Science ®Google Scholar
• Halliday C, Hoile R, Sorrell T, et al. Role of prospective screening of blood for invasive aspergillosis by polymerase chain reaction in febrile neutropenic recipients of haematopoietic stem cell transplant and patients with acute leukaemia. Br J Haematol 2006;132:478–486.
   PubMed Web of Science ®Google Scholar
• White PL, Linton CJ, Perry MD, Johnson EM, Barnes RA. The evolution and evaluation of a whole blood polymerase chain reaction assay for the detection of invasive aspergillosis in hematology patients in a routine clinical setting. Clin Infect Dis 2006;42:479–486.
   PubMed Web of Science ®Google Scholar
• Begg CB. Biases in the assessment of diagnostic tests. Stat Med 1987;6:411–423.
   PubMed Web of Science ®Google Scholar
• Reid MC, Lachs MS, Feinstein AR. Use of methodological standards in diagnostic test research: getting better but still not good. JAMA 1995;274:645–651.
   PubMed Web of Science ®Google Scholar
• Bogardus ST, Concato J, Feinstein AR. Clinical epidemiological quality in molecular genetic research: the need for methodological standards. JAMA 1999;281:1919–1926.
   PubMed Web of Science ®Google Scholar
• Lijmer JG, Mol BW, Heisterkamp S, et al. Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 1999;282:1061–1066.
   PubMed Web of Science ®Google Scholar
• Marr KA, Leisenring W. Design issues in studies evaluating diagnostic tests for aspergillosis. Clin Infect Dis 2005;41(Suppl. 6):381–386.
   PubMed Web of Science ®Google Scholar
• Guyatt GH, Tugwell PX, Feeny DH, Haynes RB, Drummond M. A framework for clinical evaluation of diagnostic technologies. CMAJ 1986;134:587–594.
   PubMed Web of Science ®Google Scholar
• Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making 1991;11: 88–94.
   PubMed Web of Science ®Google Scholar
• Moons KGM, Grobbee DE. Diagnostic studies as multivariable, prediction research. J Epidemiol Comm Health 2002;56:337–338.
   PubMed Web of Science ®Google Scholar
• Moons KGM, Biesheuvel CJ, Grobbee DE. Test research versus diagnostic research. Clin Chem 2004;50:473–476.
   PubMed Web of Science ®Google Scholar
• Lord SJ, Irwig L, Simes RJ. When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test and when do we need randomised trials? Ann Intern Med 2006;144:850–855.
   PubMed Web of Science ®Google Scholar
• Bossuyt PM, Lijmer JG, Mol BW. Randomised comparisons of medical tests: some times invalid, not always efficient. Lancet 2000;356:1844–1847.
   PubMed Web of Science ®Google Scholar
• de Graaff JC, Ubbink DT, Tijssen JGP, Legemate DA. The diagnostic randomised clinical trial is the best solution for management issues in critical limb ischemia. J Clin Epidemiol 2004;57:1111–1118.
   PubMed Web of Science ®Google Scholar
• Severens JL, Donnelly JP, Meis JFGM, deVries Robbe PF, de Pauw BE, Verweij PE. Two strategies for managing invasive aspergillosis: a decision analysis. Clin Infect Dis 1997;25:1148–1154.
   PubMed Web of Science ®Google Scholar
• Warnock DW. Fungal complication of transplantation: diagnosis, treatment and prevention. J Antimicrob Chemother 1995;36(Suppl. B):73–90.
   PubMed Web of Science ®Google Scholar
• Donnelly JP. Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go. Clin Infect Dis 2006;42:487–489.
   PubMed Web of Science ®Google Scholar
• De Pauw BE, Donnelly JP. Prophylaxis and aspergillosis - has the principle been proven? N Engl J Med 2007;356:409–411.
   PubMed Web of Science ®Google Scholar
• Maertens J, Theunissen K, Verbeken E, et al. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol 2004;126:852–860.
   PubMed Web of Science ®Google Scholar
• Wheat LJ. Rapid diagnosis of invasive aspergillosis by antigen detection. Transplant Infect Dis 2003;5:158–166.
   PubMedGoogle Scholar
• Halliday C, Wu QX, James G, Sorrell T. Development of a nested qualitative real-time PCR assay to detect Aspergillus species DNA in clinical specimens. J Clin Microbiol 2005;43:5366–5368.
   PubMed Web of Science ®Google Scholar
• Slavin MA, Szer J, Grigg AP, et al. Guidelines for the use of antifungal agents in the treatment of invasive Candida and mold infections. Intern Med J 2004;34:192–200.
   PubMed Web of Science ®Google Scholar
• Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high-risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 2005;41:1242–1250.
   PubMed Web of Science ®Google Scholar
• Jennison C, Turnball BW. Two-sided tests: introduction. Group sequential methods with applications to clinical trials. In: Jennison C, Turnball BW, editors. Boca Raton, FL: Chapman & Hall/CRC; 2000. pp 21–48.
   Google Scholar
• Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mold infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909–917.
   PubMed Web of Science ®Google Scholar
• Pocock SJ. The size of a clinical trial. Clinical trials: a practical approach. In: Pocock SJ, editor. Chichester, UK: Wiley Publications; 1983. pp 123–141.
   Google Scholar
• Kirby A, Gebski VJ, Keech AC. Determining the sample size in a clinical trial. Interpreting and reporting clinical trials. A guide to the CONSORT statement and the principles of randomised controlled trials. In: Keech A, Gebski V, Pike R, editors. Sydney: Australian Medical Publishing Company; 2007. pp 28–36.
   Google Scholar
• Bakhai A, Chhabra, Wang D. Endpoints. Clinical trials: a practical guide to design, analysis and reporting. In: Wang D, Bakhai A, editors. London: Remedica; 2006. pp 37–46.
   Google Scholar
• Gebski VJ, Marschner I, Keech AC. Specifying objectives and outcomes for clinical trials. Interpreting and reporting clinical trials. A guide to the CONSORT statement and the principles of randomised controlled trials. In: Keech A, Gebski V, Pike R, editors. Sydney: Australian Medical Publishing Company; 2007. pp 21–26.
   Google Scholar
• Hebart H, Klingspor L, Klingebiel T, et al. A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT. Bone Marrow Transplant 2009;43:553–561.
   PubMed Web of Science ®Google Scholar
• Barnes RA, White PL, Bygrave C, Evans N, Healy B, Kell J. Clinical impact of enhanced diagnosis of invasive fungal disease in high-risk haematology and stem cell transplant patients. J Clin Pathol 2009;62:64–69.
   PubMed Web of Science ®Google Scholar
• Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol 2000;110:273–284.
   PubMed Web of Science ®Google Scholar
• McLintock LA, Jordanides NE, Allan EK, et al. The use of a risk group stratification in the management of invasive fungal infections: a prospective validation. Br J Haematol 2004;124:403–404.
   PubMed Web of Science ®Google Scholar
• Klont RR, Meis JFGM, Verweij PE. Critical assessment of issues in the diagnosis of invasive aspergillosis. Clin Microbiol Infect 2001;7(Suppl. 2):32–37.
   PubMed Web of Science ®Google Scholar
• Sackett DL, Haynes RB, Guyatt GH, Tugwell P. The interpretation of diagnostic data Clinical epidemiology: a basic science for clinical medicine. In: Sackett DL, Haynes RB, Guyatt GH, Tugwell P, editors. Toronto: Little, Brown and Company; 1991. pp 69–152.
   Google Scholar
• Hope WW, Walsh TJ, Denning DW. The invasive and saprophytic syndromes due to Aspergillus spp. Med Mycol 2005;43(Suppl. 1):207–238.
   PubMed Web of Science ®Google Scholar
• Keech AC, Gebski V. Managing the resource demands of a large sample size in clinical trials: can you succeed with fewer subjects? Interpreting and reporting clinical trials. A guide to the CONSORT statement and the principles of randomised controlled trials. In: Keech A, Gebski V, Pike R, editors. Sydney: Australian Medical Publishing Company; 2007. pp 39–45.
   Google Scholar
• Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 2002;100:4358–4366.
   PubMed Web of Science ®Google Scholar
• Bradstock KF, Matthews JP, Lowenthal RM, et al. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukaemia in first remission after induction therapy containing high-dose cytarabine. Blood 2005;105:481–488.
   PubMed Web of Science ®Google Scholar
• Becker MJ, Lugtenburg EJ, Cornelissen JJ, van der Schee C, Hoogensteden HC, De Marie S. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at-risk for invasive aspergillosis. Br J Haematol 2003;121:448–457.
   PubMed Web of Science ®Google Scholar
• Yoo J-H, Choi J-H, Choi S-M, et al. Application of nucleic acid sequence-based amplification for diagnosis of and monitoring the clinical course of invasive aspergillosis in patients with hematological diseases. Clin Infect Dis 2005;40:392–398.
   PubMed Web of Science ®Google Scholar
• Millon L, Piarroux R, Deconinck E, et al. Use of real-time PCR to process the first galactomannan-positive serum sample in diagnosing invasive aspergillosis. J Clin Microbiol 2005;43:5097–5101.
   PubMed Web of Science ®Google Scholar
• Mennink-Kersten MA, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis 2004;4:349–357.
   PubMed Web of Science ®Google Scholar
• Latgé J-P. The pathobiology of Aspergillus fumigatus. Trends Microbiol 2001;9:382–389.
   PubMed Web of Science ®Google Scholar
• Balloy V, Huerre M, Latgé J-P, Chignard M. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect Immun 2005;73:494–503.
   PubMed Web of Science ®Google Scholar
• Berenguer J, Allende MC, Lee JW, et al. Pathogenesis of pulmonary aspergillosis. Granulocytopenia versus cyclosporine and methylprednisolone-induced immunosuppression. Am J Respir Crit Care Med 1995;152:1079–1086.
   PubMed Web of Science ®Google Scholar
• Duong M, Ouellet N, Simard M, Bergeron Y, Olivier M, Bergeron MG. Kinetic study of host defense and inflammatory response to Aspergillus fumigatus in steroid-induced immunosuppressed mice. J Infect Dis 1998;178:1472–1482.
   PubMed Web of Science ®Google Scholar
• Mengoli C, Cruciani M, Barnes RA, Loeffler J, Donnelly JP. Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis 2009;9:89–96.
   PubMed Web of Science ®Google Scholar
• Klingspor L, Loeffler J. Aspergillus PCR formidable challenges and progress. Med Mycol 2009;47(Suppl. 1):S241–S247.
   PubMed Web of Science ®Google Scholar
• Marr KA, Laverdiere M, Gugel A, Leisenring W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis 2005;40:1762–1769.
   PubMed Web of Science ®Google Scholar
• Glasmacher A, Prentice A, Gorschlüter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol 2003;21:4615–4626.
   PubMed Web of Science ®Google Scholar
• Winston DJ, Maziarz RT, Chandrasekar PH, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients: a multicenter randomized trial. Ann Intern Med 2003;138:705–713.
   PubMed Web of Science ®Google Scholar
• Grigg AP, Brown M, Roberts AW, Szer J, Slavin MA. A pilot study of targeted itraconazole prophylaxis in patients with graft-versus-host-disease at high-risk of invasive mold infections following allogeneic stem cell transplantation. Bone Marrow Transplant 2004;34:447–453.
   PubMed Web of Science ®Google Scholar
• Marr KA, Crippa F, Leisenring W, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood 2004;103:1527–1533.
   PubMed Web of Science ®Google Scholar
• van Burik J-AH, Ratanatharathorn V, Stepan DE, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 2004;39:1407–1416.
   PubMed Web of Science ®Google Scholar
• Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417–1427.
   PubMed Web of Science ®Google Scholar
• Bennett JE, Powers J, Walsh T. Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis 2003;36(Suppl. 3):117–122.
   Web of Science ®Google Scholar
• de Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infection Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813–1821.
   PubMed Web of Science ®Google Scholar
• Nivoix Y, Fohrer C, Fornecker L, Herbrecht R. Clinical antifungal efficacy trials in invasive aspergillosis: consensus standards for trial design and room for improvement. Med Mycol 2006;44(Suppl. 1):289–294.
   PubMed Web of Science ®Google Scholar
• Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med 1999;340:764–771.
   PubMed Web of Science ®Google Scholar
• Walsh TJ, Pappas P, Winston DJ, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fevers. N Engl J Med 2009;346:225–234.
   Web of Science ®Google Scholar
• Walsh TJ, Teppler H, Donowitz GR, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 2004;351:1391–1402.
   PubMed Web of Science ®Google Scholar
• Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408–415.
   PubMed Web of Science ®Google Scholar
• Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad Trial). Clin Infect Dis 2007;44:1289–1297.
   PubMed Web of Science ®Google Scholar
• Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008;46:327–360.
   PubMed Web of Science ®Google Scholar
• Sargent D, Allegra C. Issues in clinical trial design for tumor marker studies. Semin Oncol 2002;29:222–230.
   PubMed Web of Science ®Google Scholar