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Robust and Discordant Evidence: Methodological Lessons from Clinical Research

Published online by Cambridge University Press:  01 January 2022

Abstract

The concordance of results that are “robust” across multiple scientific modalities is widely considered to play a critical role in the epistemology of science. But what should we make of those cases where such multimodal evidence is discordant? Jacob Stegenga has recently argued that robustness is “worse than useless” in these cases, suggesting that “different kinds of evidence cannot be combined in a coherent way.” In this article I respond to this critique and illustrate the critical methodological role that robustness plays as an aim of scientific inquiry.

Type
Research Article
Copyright
Copyright © The Philosophy of Science Association

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Footnotes

I would like to thank Charles Weijer, Robert Batterman, Charles Heilig, William Wimsatt, and the anonymous reviewers of this journal for their insightful feedback on this manuscript.

References

Burman, William J., et al. 2006. “Moxifloxacin versus Ethambutol in the First 2 Months of Treatment for Pulmonary Tuberculosis.” American Journal of Respiratory and Critical Care Medicine 174:331–38.CrossRefGoogle ScholarPubMed
Chapin, Charles V. 1910. The Sources and Modes of Infection. New York: Wiley.Google Scholar
Conde, Marcus B., et al. 2009. “Moxifloxacin versus Ethambutol in the Initial Treatment of Tuberculosis: A Double-Blind, Randomised, Controlled Phase II Trial.” Lancet 373:1183–89.CrossRefGoogle ScholarPubMed
Culp, Sylvia. 1994. “Defending Robustness: The Bacterial Mesosome as a Test Case.” In PSA 1994: Proceedings of the 1994 Biennial Meeting of the Philosophy of Science Association, ed. Hull, David, Forbes, Micky, and Burian, Richard M., 4657. East Lansing, MI: Philosophy of Science Association.Google Scholar
Dorman, Susan E., et al. 2009. “Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis.” American Journal of Respiratory and Critical Care Medicine 180:273–80.CrossRefGoogle ScholarPubMed
Franklin, Allan. 2002. Selectivity and Discord: Two Problems of Experiment. Pittsburgh: University of Pittsburgh Press.Google Scholar
Freedman, Benjamin. 1987. “Equipoise and the Ethics of Clinical Research.” New England Journal of Medicine 317:141–45.CrossRefGoogle ScholarPubMed
Gillespie, Stephen, and Billington, O.. 1999. “Activity of Moxifloxacin against Mycobacteria.” Journal of Antimicrobial Chemotherapy 44:393–95.CrossRefGoogle ScholarPubMed
Gillespie, Stephen H., Gosling, Roly D., Uiso, Leonard, Sam, Noel E., Kanduma, Esther G., and McHugh, Timothy D.. 2005. “Early Bactericidal Activity of a Moxifloxacin and Isoniazid Combination in Smear-Positive Pulmonary Tuberculosis.” Journal of Antimicrobial Chemotherapy 56:1169–71.CrossRefGoogle ScholarPubMed
Gosling, Roly D., Uiso, Leonard O., Sam, Noel E., Bongard, Emily, Kanduma, Esther G., Nyindo, Mramba, Morris, Richard W., and Gillespie, Stephen H.. 2003. “The Bactericidal Activity of Moxifloxacin in Patients with Pulmonary Tuberculosis.” American Journal of Respiratory and Critical Care Medicine 168:1342–45.CrossRefGoogle ScholarPubMed
Hall, Caroline B. 2007. “The Spread of Influenza and Other Respiratory Viruses: Complexities and Conjectures.” Clinical Infectious Diseases 45:353–59.CrossRefGoogle Scholar
Hay, Michael, Thomas, David W., Craighead, John L., Economides, Celia, and Rosenthal, Jesse. 2014. “Clinical Development Success Rates for Investigational Drugs.” Nature Biotechnology 32:4051.CrossRefGoogle ScholarPubMed
Hey, Spencer P., Heilig, Charles M., and Weijer, Charles. 2013. “Accumulating Evidence and Research Organization (AERO) Model: A New Tool for Representing, Analyzing, and Planning a Translational Research Program.” Trials 14:159.CrossRefGoogle ScholarPubMed
Ji, Baohong, Lounis, Nacer, Maslo, Caroline, Truffot-Pernot, Chantal, Bonnafous, Pascale, and Grosset, Jacques. 1998. “In Vitro and In Vivo Activities of Moxifloxacin and Clinafloxacin against Mycobacterium Tuberculosis.” Antimicrobial Agents and Chemotherapy 42:2066–69.CrossRefGoogle ScholarPubMed
Johnson, J., et al. 2006. “Early and Extended Early Bactericidal Activity of Levofloxacin, Gatifloxacin and Moxifloxacin in Pulmonary Tuberculosis.” International Journal of Tuberculosis and Lung Disease 10:605–12.Google ScholarPubMed
Levins, Richard. 1966. “The Strategy of Model Building in Population Biology.” American Scientist 54:421–31.Google Scholar
Levins, Richard 1993. “A Response to Orzack and Sober: Formal Analysis and the Fluidity of Science.” Quarterly Review of Biology 68:547–55.CrossRefGoogle Scholar
Lounis, Nacer, Bentoucha, Abdelhalim, Truffot-Pernot, Chantal, Ji, Baohong, O’Brien, Richard J., Vernon, Andrew, Roscigno, Giorgio, and Grosset, Jacques. 2001. “Effectiveness of Once-Weekly Rifapentine and Moxifloxacin Regimens against Mycobacterium Tuberculosis in Mice.” Antimicrobial Agents and Chemotherapy 45:3482–86.CrossRefGoogle ScholarPubMed
Mac Kenzie, William R., et al. 2011. “Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28; Culture Conversion Is Delayed in Africa.” PLoS One 6:e18358.CrossRefGoogle ScholarPubMed
Mateo, Joaquin, Ong, Michael, Tan, David S. P., Gonzalez, Michael A., and de Bono, Johann S.. 2013. “Appraising Iniparib, the Parp Inhibitor That Never Was—What Must We Learn?Nature Reviews Clinical Oncology 10:688–96.CrossRefGoogle Scholar
Miyazaki, Eishi, Miyazaki, Miki, Chen, Jong Min, Chaisson, Richard E., and Bishai, William R.. 1999. “Moxifloxacin (bay12-8039), a New 8-Methoxyquinolone, Is Active in a Mouse Model of Tuberculosis.” Antimicrobrial Agents and Chemotherapy 43:8589.CrossRefGoogle Scholar
Nuermberger, Eric L., Yoshimatsu, Tetsuyuki, Tyagi, Sandeep, O’Brien, Richard J., Vernon, Andrew N., Chaisson, Richard E., Bishai, William R., and Grosset, Jacques H.. 2004. “Moxifloxacin-Containing Regimen Greatly Reduces Time to Culture Conversion in Murine Tuberculosis.” American Journal of Respiratory and Critical Care Medicine 169:421–26.CrossRefGoogle ScholarPubMed
Orzack, Steven H., and Sober, Elliott. 1993. “A Critical Assessment of Levins’s ‘The Strategy of Model Building in Population Biology’ (1966).” Quarterly Review of Biology 68:533–46.CrossRefGoogle Scholar
Pletz, Mathias W. R., Roux, Andres De, Roth, Andreas, Neumann, Karl-Heinz, Mauch, Harald, and Lode, Hartmut. 2004. “Early Bactericidal Activity of Moxifloxacin in Treatment of Pulmonary Tuberculosis: A Prospective, Randomized Study.” Antimicrobial Agents and Chemotherapy 48:780–82.CrossRefGoogle ScholarPubMed
Rasmussen, Nicolas. 1993. “Facts, Artifacts, and Mesosomes: Practicing Epistemology with the Electron Microscope.” Studies in History and Philosophy of Science A 24:227–65.CrossRefGoogle Scholar
Rustomjee, R., et al. 2008. “A Phase II Study of the Sterilising Activities of Ofloxacin, Gatifloxacin and Moxifloxacin in Pulmonary Tuberculosis.” International Journal of Tuberculosis and Lung Disease 12:128–38.Google ScholarPubMed
Shandil, Radha K., Jayaram, Ramesh, Kaur, Parvinder, Gaonkar, Sheshagiri, Suresh, B. L., Mahesh, B. N., Jayashree, R., Nandi, Vrinda, Bharath, Sowmya, and Balasubramanian, V.. 2007. “Moxifloxacin, Ofloxacin, Sparfloxacin, and Ciprofloxacin against Mycobacterium Tuberculosis: Evaluation of In Vitro and Pharmacodynamic Indices That Best Predict In Vivo Efficacy.” Antimicrobial Agents and Chemotherapy 51:576–82.CrossRefGoogle ScholarPubMed
Soler, Léna, Trizio, Emiliano, Nickles, Thomas, and Wimsatt, William, eds. 2012. Characterizing the Robustness of Science: After the Practice Turn in Philosophy of Science. Dordrecht: Springer.CrossRefGoogle Scholar
Staley, Kent W. 2004. “Robust Evidence and Secure Evidence Claims.” Philosophy of Science 71:467–88.CrossRefGoogle Scholar
Stass, H., Dalhoff, A., Kubitza, D., and Schühly, U.. 1998. “Pharmacokinetics, Safety, and Tolerability of Ascending Single Doses of Moxifloxacin, a New 8-Methoxy Quinolone, Administered to Healthy Subjects.” Antimicrobial Agents and Chemotherapy 42:2060–65.CrossRefGoogle ScholarPubMed
Steenwinkel, Jurriaan E. M., de Knegt, Gerjo J., Marian, T., van Belkum, Alex, Verbrugh, Henri A., Kremer, Kristin, van Soolingen, Dick, and Bakker-Woudenberg, Irma A. J. M.. 2010. “Time-Kill Kinetics of Anti-tuberculosis Drugs, and Emergence of Resistance, in Relation to Metabolic Activity of Mycobacterium Tuberculosis.” Journal of Antimicrobial Chemotherapy 65:2582–89.CrossRefGoogle ScholarPubMed
Stegenga, Jacob. 2009. “Robustness, Discordance, and Relevance.” Philosophy of Science 76:650–61.CrossRefGoogle Scholar
Stegenga, Jacob 2012. “Rerum Concordia Discors: Robustness and Discordant Multimodal Evidence.” In Soler et al. 2012, 207–26.Google Scholar
Wang, J. Y., Wang, J. T., Tsai, T., Hsu, C., Yu, C., Hsueh, P., Lee, L., and Yang, P.. 2009. “Adding Moxifloxacin Is Associated with a Shorter Time to Culture Conversion in Pulmonary Tuberculosis.” International Journal of Tuberculosis and Lung Disease 14:6571.Google Scholar
Weber, Thomas P., and Stilianakis, Nikolaos I.. 2008. “Inactivation of Influenza A Viruses in the Environment and Modes of Transmission: A Critical Review.” Journal of Infection 57:361–73.CrossRefGoogle ScholarPubMed
Weijer, Charles, and Miller, Paul B.. 2004. “When Are Research Risks Reasonable in Relation to Anticipated Benefits?Nature Medicine 10:570–73.CrossRefGoogle ScholarPubMed
Wimsatt, William. 1980. “Reductionist Research Strategies and Their Biases in the Units of Selection Controversy.” In Scientific Discovery: Case Studies, ed. Nickles, Thomas, 213–59. Dordrecht: Reidel.Google Scholar
Wimsatt, William. 1981. “Robustness, Reliability and Overdetermination.” In Scientific Inquiry and the Social Sciences, ed. Brewer, M., 124–63. San Francisco: Jossey-Bass.Google Scholar
Wimsatt, William. 2007. Re-engineering Philosophy for Limited Beings: Piecewise Approximations to Reality. Cambridge, MA: Harvard University Press.CrossRefGoogle Scholar
Yoshimatsu, Tetsuyuki, Nuermberger, Eric, Tyagi, Sandeep, Chaisson, Richard, Bishai, William, and Grosset, Jacques. 2002. “Bactericidal Activity of Increasing Daily and Weekly Doses of Moxifloxacin in Murine Tuberculosis.” Antimicrobial Agents and Chemotherapy 46:1875–79.CrossRefGoogle ScholarPubMed