pp 1–27 | Cite as

Invisible work, actors, and knowledge: An analysis of a clinical trial for a vaccine to stop smoking

  • Anna Wolters
  • Guido de Wert
  • Onno C. P. van Schayck
  • Klasien Horstman
Original Article


Experimental vaccines to treat smoking are tested in randomised clinical trials (RCTs) where participants receive real or placebo ‘nicotine vaccination’ plus additional support. RCTs are a standard method within the current conventions of evidence-based medicine. As yet, nicotine vaccines did not ‘work’ better than placebos. Interestingly, several trials showed high overall quit smoking rates. Understanding lifestyle change, scholars argue, requires insights into sociocultural context and embodied experiences. The question then arises how knowledge claims about behaviour change are made in the controlled setting of a clinical trial. Drawing from science and workplace studies, this paper analyses the case of a nicotine vaccination trial. With document analysis, fieldwork and 77 interviews we compared the daily practice of fact-making with the knowledge claims as represented front stage. Our qualitative study suggests that staff and volunteers performed much work in attending to social processes of behaviour change and trial participation. These efforts were underrepresented in the protocol-centred format of trial reports. The knowledge work of assistants in particular was largely absent in official documents. Accounting for experiments with nicotine and other lifestyle vaccines will require an integrative trial design that combines the biomedical rationale with perspectives from the humanities and social sciences.


Lifestyle vaccination Invisible work Research assistants Knowledge claims Health behaviour change Clinical trial design 



We thank the interviewed research assistants, researchers, research participants, and their relatives for being kind enough to have shared with us their experiences and views on testing nicotine vaccination in a clinical trial.

Compliance with ethical standards

Conflict of interest

Competing interests—intellectual or financial—in the research detailed in the manuscript: Anna Wolters: none. Guido de Wert: none. Onno van Schayck has received unrestricted grants for research funding from Pfizer, Boehringer Ingelheim, and Nabi. Klasien Horstman: none.

Ethical approval

This is to confirm that the manuscript comprises original material that is not under review elsewhere and that the study on which this research is based has received ethical approval from the Netherlands Central Committee for Research involving Human Subjects (CCMO).


  1. Adams, V. (ed.). 2016. Metrics: What counts in global health. Durham: Duke University Press.Google Scholar
  2. Armstrong, D. 2007. Professionalism, indeterminacy and the EBM project. BioSocieties 2: 73–84.CrossRefGoogle Scholar
  3. American Statistical Association. 2016. American Statistical Association releases statement on statistical significance and p-values.Google Scholar
  4. Bachmann, M., and G. Jennings. 2011. Therapeutic vaccines for chronic diseases. Philosophical Transactions of the Royal Society B: Biological Sciences 366: 2815–2822.CrossRefGoogle Scholar
  5. Bell, K. 2013. Whither tobacco studies? Sociology Compass 7: 34–44.CrossRefGoogle Scholar
  6. Bevans, M., C. Hastings, L. Wehrlen, G. Cusack, A.M. Matlock, C. Miller-Davis, et al. 2011. Defining clinical research nursing practice: Results of a role delineation study. Clinical and Translational Science 4: 421–427.CrossRefGoogle Scholar
  7. Bolt, T., and F. Huisman. 2015. Evidence-based medicine in crisis? TGE 25: 102–107.Google Scholar
  8. Bonell, C., A. Fletcher, M. Morton, T. Lorenc, and L. Moore. 2012. Realist randomised controlled trials: A new approach to evaluating complex public health interventions. Social Science and Medicine 75: 2299–2306.CrossRefGoogle Scholar
  9. Bonell, C., A. Fletcher, M. Morton, T. Lorenc, and L. Moore. 2013. Methods don’t make assumptions, researchers do: A response to Marchal et al. Social Science and Medicine 94: 81–82.CrossRefGoogle Scholar
  10. Bothwell, L.E., J.A. Greene, S.H. Podolsky, and D.S. Jones. 2016. Assessing the gold standard - lessons from the history of RCTs. New England Journal of Medicine 374: 2175–2181.CrossRefGoogle Scholar
  11. Boulton, M.G., and N. Hopewell. 2017. The workforce delivering translational and applied health research: A cross sectional survey of their characteristics, studies and responsibilities. Collegian 24: 469–477.CrossRefGoogle Scholar
  12. Brueton, V.C., J. Tierney, S. Stenning, S. Harding, S. Meredith, I. Nazareth, et al. 2013. Strategies to improve retention in randomised trials. The Cochrane Database of Systematic Reviews 12: 000032.Google Scholar
  13. Cartwright, N. 2007. Are RCTs the gold standard? BioSocieties 2: 11–20.CrossRefGoogle Scholar
  14. Castro, K., M. Bevans, C. Miller-Davis, G. Cusack, F. Loscalzo, A.M. Matlock, et al. 2011. Validating the clinical research nursing domain of practice. Oncology Nursing Forum 38: E72–E80.CrossRefGoogle Scholar
  15. Cohn, S. 2014. From health behaviours to health practices: An introduction. Sociology of Health & Illness 36: 157–162.CrossRefGoogle Scholar
  16. Cornuz, J., S. Zwahlen, W. Jungi, J. Osterwalder, K. Klingler, G. van Melle, et al. 2008. A vaccine against nicotine for smoking cessation. PLoS ONE 3: e2547.CrossRefGoogle Scholar
  17. Craig, P., P. Dieppe, S. Macintyre, S. Michie, I. Nazareth, and M. Petticrew. 2008. Developing and evaluating complex interventions: The new Medical Research Council guidance. BMJ 337: a1655.CrossRefGoogle Scholar
  18. Deaton, A., and N. Cartwright. 2016. Understanding and Misunderstanding Randomized Controlled Trials (No. w22595). National Bureau of Economic Research.Google Scholar
  19. De Vries, R., and T. Lemmens. 2006. The social and cultural shaping of medical evidence: Case studies from pharmaceutical research and obstetric science. Social Science and Medicine 62: 2694–2706.CrossRefGoogle Scholar
  20. Doing, P. 2008. Give me a laboratory and I will raise a discipline: the past, present, and future (politics) of laboratory studies or an accounting error in STS. In The handbook of science and technology studies, ed. E.J. Hackett, O. Amsterdamska, M.E. Lynch, and J. Wajcman, 279–297. Cambridge: MIT.Google Scholar
  21. European Commission. n.d. Responsible research & innovation. Horizon 2020. The EU Framework Programme for Research and Innovation.Google Scholar
  22. Epstein, S. 1995. The construction of lay expertise: AIDS activism and the forging of credibility in the reform of clinical trials. Science, Technology and Human Values 20: 408–437.CrossRefGoogle Scholar
  23. Epstein, S. 1996. Impure science: AIDS, activism, and the politics of knowledge. Berkeley: University of California Press.Google Scholar
  24. Epstein, S. 2008. Inclusion: The politics of difference in medical research. Chicago: University of Chicago Press.Google Scholar
  25. Fisher, J.A. 2009. Medical research for hire: The political economy of pharmaceutical clinical trials. New Brunswick: Rutgers University Press.Google Scholar
  26. Fisher, J.A. 2010. Re-inscribing gender in new modes of medical expertise: The investigator–coordinator relationship in the clinical trials industry. Gender, Work & Organization 17: 150–173.CrossRefGoogle Scholar
  27. Frohlich, K., E. Mykhalovskiy, B.D. Poland, R. Haines-Saah, and J. Johnson. 2012. Creating the socially marginalised youth smoker: The role of tobacco control. Sociology of Health & Illness 34: 978–993.CrossRefGoogle Scholar
  28. Fulurija, A., T. Lutz, K. Sladko, M. Osto, P. Wielinga, M. Bachmann, et al. 2008. Vaccination against GIP for the treatment of obesity. PLoS ONE 3: e3163.CrossRefGoogle Scholar
  29. Geraci, A.A., A. Brunt, and C. Marihart. 2014. The work behind weight-loss surgery: A qualitative analysis of food intake after the first two years post-op. ISRN Obesity. Scholar
  30. Getz, K.A. 2008. Restoring public confidence in clinical research. The Monitor 22: 59–62.Google Scholar
  31. Goffman, E. 1959. The presentation of self in everyday life. New York: Anchor.Google Scholar
  32. Goodman, S.N. 2016. Aligning statistical and scientific reasoning. Science 352: 1180–1181.CrossRefGoogle Scholar
  33. Green, J., and R. Labonté (eds.). 2008. Critical perspectives in public health. London: Routledge.Google Scholar
  34. Greenhalgh, T., J. Howick, and N. Maskrey. 2014. Evidence based medicine: A movement in crisis? BMJ 348: g3725.CrossRefGoogle Scholar
  35. Hanson, S., J. Cross, and A. Jones. 2016. Promoting physical activity interventions in communities with poor health and socio-economic profiles: A process evaluation of the implementation of a new walking group scheme. Social Science & Medicine 169:77–85.CrossRefGoogle Scholar
  36. Harbers, M.M.E. 2010. Regional differences in smoking behavior in the Netherlands. RIVM: VTV/NKV. Bilthoven.Google Scholar
  37. Hartmann-Boyce, J., K. Cahill, D. Hatsukami, and J. Cornuz. 2012. Nicotine vaccines for smoking cessation. The Cochrane Library 8: CD007072.Google Scholar
  38. Hawe, P. 2015. Lessons from complex interventions to improve health. Annual Review of Public Health 36: 307–323.CrossRefGoogle Scholar
  39. Helgesson, C.-F. 2010. From dirty data to credible scientific evidence: Some practices used to clean data in large randomised clinical trials. In Medical proofs, social experiments: clinical trials in shifting contexts, ed. C. Will and T. Moreira, 49–66. Farnham: Ashgate.Google Scholar
  40. Hoogsteder, P., D. Kotz, P. van Spiegel, W. Viechtbauer, and O. van Schayck. 2014. Efficacy of the nicotine vaccine 3′-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation. Addiction 109: 1252–1259.CrossRefGoogle Scholar
  41. Horstman, K., and R. Houtepen. 2005. [Struggling with healthy living] Worstelen met gezond leven. Amsterdam: Ethiek in de preventie van hart- en vaatziekten.Google Scholar
  42. ICMJE. 2016. Defining the role of authors and contributors. n.p.: International Committee of Medical Journal Editors.Google Scholar
  43. Ioannidis, J.P.A. 2016. Evidence-based medicine has been hijacked: A report to David Sackett. Journal of Clinical Epidemiology 73: 82–86.CrossRefGoogle Scholar
  44. Irani, L. 2015a. The cultural work of microwork. New Media & Society 17 (5): 720–739.CrossRefGoogle Scholar
  45. Irani, L. 2015b. Difference and dependence among digital workers: The case of Amazon Mechanical Turk. South Atlantic Quarterly 114 (1): 225–234.CrossRefGoogle Scholar
  46. Irani, L., and M. Sengul-Jones. 2015. Difference work: A conversation with Lilly Irani. Catalyst:Feminism, Theory, Technoscience 1 (1): 1–14.CrossRefGoogle Scholar
  47. Jamal, F., A. Fletcher, N. Shackleton, D. Elbourne, R. Viner, and C. Bonell. 2015. The three stages of building and testing mid-level theories in a realist RCT: A theoretical and methodological case-example. Trials 16: 1–10.CrossRefGoogle Scholar
  48. Jespersen, A.P., J. Bønnelycke, and H.H. Eriksen. 2014. Careful science? Bodywork and care practices in randomised clinical trials. Sociology of Health & Illness 36: 655–669.CrossRefGoogle Scholar
  49. Kelly, M.P., I. Heath, J. Howick, and T. Greenhalgh. 2015. The importance of values in evidence-based medicine. BMC Medical Ethics 16: 1–8.CrossRefGoogle Scholar
  50. Knorr-Cetina, K. 1981. The manufacture of knowledge: An essay on the constructivist and contextual nature of science. Oxford/New York: Pergamon Press.Google Scholar
  51. Knorr-Cetina, K. 1999. Epistemic cultures: How the sciences make knowledge. Cambridge: Harvard University Press.Google Scholar
  52. Latour, B. 1993. We have never been modern. Cambridge: Harvard University Press.Google Scholar
  53. Latour, B., and S. Woolgar. 1986. Laboratory life: The construction of scientific facts. Princeton: Princeton University Press.Google Scholar
  54. Lawton, J., N. Jenkins, J. Darbyshire, R. Holman, A. Farmer, and N. Hallowell. 2011. Challenges of maintaining research protocol fidelity in a clinical care setting: A qualitative study of the experiences and views of patients and staff participating in a randomized controlled trial. Trials 12: 108.CrossRefGoogle Scholar
  55. Leigh Star, S. 1991. Invisible work and silenced dialogues in knowledge representation. In Women, work and computerization, ed. I. Eriksson, B. Kitchenham, and K. Tijdens, 81–92. Amsterdam: North-Holland.Google Scholar
  56. Lemmens, T. 2013. Pharmaceutical knowledge governance: A human rights perspective. Journal of Law Medicine & Ethics 41: 163–184.CrossRefGoogle Scholar
  57. Luff, P., J. Hindmarsh, and C. Heath (eds.). 2000. Workplace studies: Recovering work practice and informing system design. Cambridge: Cambridge University Press.Google Scholar
  58. Mair, M., and C. Kierans. 2007. Critical reflections on the field of tobacco research: The role of tobacco control in defining the tobacco research agenda. Critical Public Health 17: 103–112.CrossRefGoogle Scholar
  59. Marchal, B., G. Westhorp, G. Wong, S. Van Belle, T. Greenhalgh, G. Kegels, et al. 2013. Realist RCTs of complex interventions – an oxymoron. Social Science and Medicine 94: 124–128.CrossRefGoogle Scholar
  60. Masterson-Algar, P., C.R. Burton, M.C. Brady, A. Nicoll, C.E. Clarke, C. Rick, et al. 2017. The PD COMM trial: A protocol for the process evaluation of a randomised trial assessing the effectiveness of two types of SLT for people with Parkinson’s disease. Trials 18: 397.CrossRefGoogle Scholar
  61. Metzl, J., and A. Kirkland. 2010. Against health. New York: New York UP.Google Scholar
  62. Miller, C.L., K. Mott, M. Cousins, S. Miller, A. Johnson, T. Lawson, et al. 2017. Integrating consumer engagement in health and medical research—An Australian framework. Health Research Policy and Systems 15: 9.CrossRefGoogle Scholar
  63. Mol, A. 2013. Mind your plate! The ontonorms of Dutch dieting. Social Studies of Science 43: 379–396.CrossRefGoogle Scholar
  64. Moore, G.F., S. Audrey, M. Barker, L. Bond, C. Bonell, W. Hardeman, et al. 2015. Process evaluation of complex interventions: Medical Research Council guidance. BMJ 350: h1258.CrossRefGoogle Scholar
  65. MRC. 2000. A framework for the development and evaluation of RCTs for complex interventions to improve health. London: MRC.Google Scholar
  66. Mueller, M.-R. 2004. Involvement and (potential) influence of care providers in the enlistment phase of the informed consent process: the case of aids clinical trials. Nursing Ethics 11: 42–52.CrossRefGoogle Scholar
  67. Mueller, M.-R. 2006. The work and occupational trajectories of clinical trials research. Journal of Applied Social Science 23: 44–52.Google Scholar
  68. Nabi. 2011. Nabi biopharmaceuticals announces results of first NicVAX(R) phase III clinical trial. El Segundo: Nasdaq GlobeNewswire.Google Scholar
  69. Nabi/MUMC + . (2009). Protocol Nabi-4508 Phase 2B NicVAX study. Rockville/Maastricht.Google Scholar
  70. Nabi/MUMC + . (n.d.-a). Job vacancy NicVAX research assistants. Maastricht: MUMC + .Google Scholar
  71. Nabi/MUMC + . (n.d.-b). NicVAX study. Form Counselling 2 (phone).Google Scholar
  72. Nachtigal, A., and C.A. Kidron. 2015. Existential multiplicity and the late-modern smoker: Negotiating multiple identities in a support group for smoking cessation. Sociology of Health & Illness 37 (3): 452–467.CrossRefGoogle Scholar
  73. Nature. 2016. Randomized controlled trials. Scholar
  74. NWO. 2017. Programme responsible innovation. Netherlands Organisation for Scientific Research NWO.Google Scholar
  75. Oakley, A., V. Strange, C. Bonell, E. Allen, and J. Stephenson. 2006. Process evaluation in randomised controlled trials of complex interventions. BMJ 332: 413–416.CrossRefGoogle Scholar
  76. Okwaro, F.M., C.I.R. Chandler, E. Hutchinson, C. Nabirye, L. Taaka, M. Kayendeke, et al. 2015. Challenging logics of complex intervention trials: Community perspectives of a health care improvement intervention in rural Uganda. Social Science and Medicine 131: 10–17.CrossRefGoogle Scholar
  77. Ophir, A., and S. Shapin. 1991. The place of knowledge. A methodological survey. Science in Context 4: 3–22.Google Scholar
  78. Oudshoorn, N. 2008. Diagnosis at a distance: The invisible work of patients and healthcare professionals in cardiac telemonitoring technology. Sociology of Health & Illness 30: 272–288.CrossRefGoogle Scholar
  79. Reynolds, J., D. DiLiberto, L. Mangham-Jefferies, E.K. Ansah, S. Lal, H. Mbakilwa, et al. 2014. The practice of ‘doing’ evaluation: Lessons learned from nine complex intervention trials in action. Implementation Science 9: 75.CrossRefGoogle Scholar
  80. Rip, A. 2016. The clothes of the emperor. An essay on RRI in and around Brussels. Journal of Responsible Innovation 3: 290–304.CrossRefGoogle Scholar
  81. Rushforth, A. 2015. Meeting pragmatism halfway: Making a pragmatic clinical trial protocol. Sociology of Health & Illness 37: 1285–1298.CrossRefGoogle Scholar
  82. Savransky, M., and M. Rosengarten. 2016. What is nature capable of? Evidence, ontology and speculative medical humanities. Medical Humanities 42: 166–172.CrossRefGoogle Scholar
  83. Seale, C. 2004. Researching society and culture. London: Sage.Google Scholar
  84. Shapin, S. 1989. The invisible technician. American Scientist 77 (6): 554–563.Google Scholar
  85. Shapin, S., S. Schaffer, and T. Hobbes. 1985. Leviathan and the air-pump. Princeton: Princeton University Press.Google Scholar
  86. Smith, K.E. 2013. Beyond evidence-based policy in public health: The interplay of ideas. Basingstoke: Palgrave.CrossRefGoogle Scholar
  87. Squires, A. 2009. Methodological challenges in cross-language qualitative research: A research review. International Journal of Nursing Studies 46: 277–287.CrossRefGoogle Scholar
  88. Stanley, J.P. 1978. Forced inference: Uses and abuses of the passive. Paper in Linguistics 10: 299–311.CrossRefGoogle Scholar
  89. Star, S.L. 1995. Ecologies of knowledge: Work and politics in science and technology. Albany: State University of New York Press.Google Scholar
  90. Star, S.L., and A. Strauss. 1999. Layers of silence, arenas of voice: The ecology of visible and invisible work. Computer Supported Cooperative Work (CSCW) 8 (1–2): 9–30.CrossRefGoogle Scholar
  91. Stilgoe, J., R. Owen, and P. Macnaghten. 2013. Developing a framework for responsible innovation. Research Policy 42: 1568–1580.CrossRefGoogle Scholar
  92. Suchman, L. 2000. Making a case: ‘Knowledge’ and ‘routine’ work in document production. In Workplace studies, ed. P. Luff, J. Hindmarch, and C. Heath, 29–45. Cambridge: CUP.CrossRefGoogle Scholar
  93. Taebi, B., A. Correljé, E. Cuppen, M. Dignum, and U. Pesch. 2014. Responsible innovation as an endorsement of public values: The need for interdisciplinary research. Journal of Responsible Innovation 1: 118–124.CrossRefGoogle Scholar
  94. Timmermans, S. 2011. The joy of science: Finding success in a ‘failed’ randomized clinical trial. Science, Technology and Human Values 36: 549–572.CrossRefGoogle Scholar
  95. Timmermans, S., and M. Berg. 1997. Standardization in action: Achieving local universality through medical protocols. Social Studies of Science 27: 273–305.CrossRefGoogle Scholar
  96. Tointon, A. 2016. The Pulse on Patient Recruitment. The issue of patient retention in clinical trials. Boston: CenterWatch.Google Scholar
  97. Tonstad, S., E. Heggen, H. Giljam, P.-Å. Lagerbäck, P. Tønnesen, L.D. Wikingsson, et al. 2013. Niccine®, a nicotine vaccine, for relapse prevention. Nicotine & Tobacco Research 15: 1492–1501.CrossRefGoogle Scholar
  98. van Schayck, C.P. 2006. Grant application: A new vaccine for the treatment and prevention of nicotine addiction. Efficacy, mechanism and ethical implications. Netherlands: ZonMw, the Netherlands Organisation for Health Research and Development.Google Scholar
  99. Viney, W., F. Callard, and A. Woods. 2015. Critical medical humanities: Embracing entanglement, taking risks. Medical Humanities 41: 2–7.CrossRefGoogle Scholar
  100. Vocci, F., and C. Chiang. 2001. Vaccines against nicotine. CNS Drugs 15: 505–514.CrossRefGoogle Scholar
  101. Visser, S.S., I. Hutter, and H. Haisma. 2016. Building a framework for theory-based ethnographies for studying intergenerational family food practices. Appetite 97: 49–57.CrossRefGoogle Scholar
  102. Vogel, E., and A. Mol. 2014. Enjoy your food: On losing weight and taking pleasure. Sociology of Health & Illness 36: 305–317.CrossRefGoogle Scholar
  103. von Schomberg, R. 2013. A vision of responsible research and innovation. In Responsible innovation, ed. R. Owen, J. Bessant, and M. Heintz, 51–74. London: Wiley.CrossRefGoogle Scholar
  104. Wahlberg, A., and L. McGoey. 2007. An elusive evidence base: The construction and governance of randomized controlled trials. Biosocieties (special issue on RCTs) 2: 1–10.Google Scholar
  105. Wajcman, J. 1995. Feminist theories of technology. In Handbook of science and technology studies, ed. S. Jasanoff, G.E. Markle, J.C. Petersen, and T.J. Pinch, 189–204. Thousand Oaks: SAGE.Google Scholar
  106. Wajcman, J. 2010. Feminist theories of technology. Cambridge Journal of Economics 34 (1): 143–152.CrossRefGoogle Scholar
  107. Weaver, R.R., M. Lemonde, N. Payman, and W.M. Goodman. 2014. Health capabilities and diabetes self-management: The impact of economic, social, and cultural resources. Social Science and Medicine 102: 58–68.CrossRefGoogle Scholar
  108. Webster, A., C. Haddad, and C. Waldby. 2011. Experimental heterogeneity and standardisation: Stem cell products and the clinical trial process. Biosocieties 6: 401–419.CrossRefGoogle Scholar
  109. Wilkes, L., D. Jackson, C. Miranda, and R. Watson. 2012. The role of clinical trial nurses: An Australian perspective. Collegian 19: 239–246.CrossRefGoogle Scholar
  110. Will, C. 2007. The alchemy of clinical trials. Biosocieties 2: 85–99.CrossRefGoogle Scholar
  111. Will, C., and T. Moreira (eds.). 2010. Medical proofs, social experiments: Clinical trials in shifting contexts. Farnham: Ashgate.Google Scholar
  112. Will, C., and K. Weiner. 2014. Sustained multiplicity in everyday cholesterol reduction: Repertoires and practices in talk about ‘healthy living’. Sociology of Health & Illness 36: 291–304.CrossRefGoogle Scholar
  113. ZonMW. n.d. Project: A new vaccine for the treatment and prevention of nicotine addiction. Scholar

Copyright information

© Springer Nature Limited 2018

Authors and Affiliations

  • Anna Wolters
    • 1
  • Guido de Wert
    • 1
  • Onno C. P. van Schayck
    • 2
  • Klasien Horstman
    • 1
  1. 1.CAPHRI School for Public Health and Primary Care, Department of Health, Ethics, and SocietyMaastricht UniversityMaastrichtThe Netherlands
  2. 2.CAPHRI School for Public Health and Primary Care, Department of General PracticeMaastricht UniversityMaastrichtThe Netherlands

Personalised recommendations