Synthetic certainization in medical controversy: Evidence synthesis, NICE recommendations and the drug-device complex in stroke prevention
DOI:
https://doi.org/10.55016/08mb7908Keywords:
atrial fibrillation, controversy, coagulometer, evidence synthesis, synthetic certainizationAbstract
The National Institute for Health and Care Excellence (NICE) recommends rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation in England. While not a directive to practitioners, that advice is widely regarded as authoritative and intended to guide practice. Yet a medical device, INRatio2-PT for monitoring coagulation/blood-clotting and producing crucial data on rivaroxaban in its key clinical trial, was defective. Following discovery of the defective device, a medical controversy about the therapeutic value of rivaroxaban ensued. Drawing on social science theories of medical controversies, such as ‘chronic contestation’, ‘closure’, ‘corporate bias’, and ‘countervailing powers’, this article describes the unfolding of the INRatio2-PT/rivaroxaban controversy and seeks to explain it. We explore the role of key protagonists based on documentary and interview data. Our findings about the media partly support ‘countervailing powers’ theory, while those regarding industry and regulators support ‘corporate bias’ theory. We found little evidence of chronic contestation of medical knowledge-claims. Rather, we contend that a sociological process of closure through synthetic certainization of knowledge-claims that rivaroxaban is efficacious and cost-effective evolved via the combined political power and interests of the medical-industrial complex, capitalist industry, and the regulatory state. Synthetic certainization, together with a regulatory ideological commitment to innovation, curtailed contestation and discouraged the medical profession from facing troubling uncertainties.
References
Abraham, J. (1994) Bias in science and medical knowledge: the Opren controversy. Sociology, 28(3), 717-736. https://doi.org/10.1177/0038038594028003005
Abraham, J. (1995) Science, politics and the pharmaceutical industry. UCL Press.
Abraham, J. (2009) Partial progress: Governing the pharmaceutical industry and the NHS, 1948-2008. Journal of Health Politics, Policy and Law, 34(6), 931–977. https://doi.org/10.1215/03616878-2009-032
Abraham, J. (2010) Pharmaceuticalization of society in context. Sociology, 44(4), 603-622. https://doi.org/10.1177/0038038510369368
Abraham, J., & Balendran, G. (2025) The political sociology of NICE: Investigating pharmaceutical cost-effectiveness regulation in the UK. Sociology of Health & Illness, 47:e13878 https://doi.org/10.1111/1467-9566.13878
Abraham, J., & Lewis, G. (2000) Regulating medicines in Europe. Routledge.
Abraham, J., & Sheppard, J. (1998) International comparative analysis and explanation in medical sociology: De-mystifying the Halcion anomaly. Sociology, 32(1), 141-162. https://doi.org/10.1177/0038038598032001009
Alere (2016) Letter to healthcare professionals dated 26th July 2016 regarding urgent medical-device recall (Alere INRatio/INRatio2 PT/INR Monitoring System). US Department of Health and Human Services. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm?id=148141
AstraZeneca (2003, Dec 23rd) Exanta (Ximelagatran) receives first approval. Press Release. AstraZeneca. https://news.cision.com/astrazeneca/r/exanta--ximelagatran--receives-first-approval,c91226
Bayer (2016, Sept 29th) Bayer comments on article in BMJ regarding Xarelto. News Release. https://www.investor.bayer.de/en/nc/news/archive/investor-news-2016/investor-news-2016/?tx_news_pi1%5Bnews%5D=1933&cHash=2055ce97671c63a63797c45d2a2315cc (Accessed 14 July 2018)
Bertotti, A. M., & Miner, S. A. (2019) Constructing contentious and non-contentious facts: How gynecology textbooks create certainty around pharma-contraceptive safety. Social Studies of Science, 49(2), 245-263. https://doi.org/10.1177/0306312719834676
Boehringer Ingelheim (2009) NICE Single-Technology-Appraisal specification for manufacturer/sponsor submission of evidence.
Boehringer Ingelheim (2025) 2024 highlights. https://www.boehringer-ingelheim.com/about-us/sustainable-development/sustainability-hub/files/common/BOE_Highlights_2024_EN.pdf
Brante, T., & Elzinga, A. (1990) Towards a theory of scientific controversies. Science & Technology Studies, 3(2), 33-46. https://doi.org/10.23987/sts.55012
Busfield, J. (2010) ‘A pill for every ill’: Explaining the expansion in medicine use. Social Science & Medicine, 70 (6), 934-41. https://doi.org/10.1016/j.socscimed.2009.10.068
Charlton, V. (2025) Innovation, values and NICE’s changing societal role. In P. Littlejohns & K. Syrett (Eds.), NICE at 25: A quarter century of evidence, values and innovation in health (pp. 67-89). Routledge.
Cohen, D. (2016) Manufacturer failed to disclose faulty device in rivaroxaban trial. BMJ 354, i5131. https://doi.org/10.1136/bmj.i5131
Coppock, K. (2019, March 26th) Litigation resolved with $775M settlement for patients prescribed blood-thinner. Pharmacy Times. https://www.pharmacytimes.com/view/litigation-resolved-with-775m-settlement-for-patients-prescribed-blood-thinner (Accessed 25 August 2025)
Daiichi-Sankyo (2024) Value report 2024. https://www.daiichisankyo.com/files/investors/library/annual_report/index/pdf/VR2024/VR2024_EN_full.pdf (Accessed 2 March 2026)
Davis, J. (2012, Jan 10th) Xarelto and Pradaxa stumble at high UK reimbursement hurdles. Pink Sheet. https://insights.citeline.com/PS073243/Xarelto-And-Pradaxa-Stumble-At-High-UK-Reimbursement-Hurdles/
Davis, C., & Abraham, J. (2013) Unhealthy pharmaceutical regulation: Innovation, politics and promissory science. Palgrave.
Dyer, O. (2019) Bayer and Janssen pay 775m to settle Xarelto misinformation claims. BMJ, 364, 1413. https://doi.org/10.1136/bmj.l1413
EMA (2016a, Feb 5th) CHMP Assessment report, Xarelto (rivaroxaban), Procedure No. EMEA/H/C/000944/LEG-037.
EMA (2016b, Sept 16th) CHMP Meeting minutes for 18-21 July 2016, EMA/CHMP/623490/2016.
Faulkner, A. (2009) Medical technology into healthcare and society: A sociology of devices, innovation and governance. Palgrave Macmillan.
FDA (2002) Premarket notification: 510(k) summary (K020679). Submitted by Hemo-Sense Inc. Available at http://inratiorecall.com/wp-content/uploads/2015/02/INRatio-510k-FDA-K020679.pdf (Accessed 17 July 2018)
FDA (2005, Oct 4th) Warning letter, INRatio and clinically significant erroneous INR values, to James D, Merselis, President-CEO, HemoSense Corporation. Available at https://www.sec.gov/Archives/edgar/data/1127393/000119312505200443/dex991.htm
FDA (2006, Nov 29th) Warning letter, INRatio and failure to investigate complaints involving discrepant results between INRatio INR and LAB INR, to James D, Merselis, President-CEO, HemoSense Corporation.
FDA (2014a) Recalls, market withdrawal, & safety alerts; industry guidance for recalls; recalls background and definitions. https://www.fda.gov/Safety/Recalls/IndustryGuidance/ucm129337.htm
FDA (2014b, Dec 5th) Alere San Diego Inc., Alere INRatio and INRatio2 PT/INR Monitor System (professional and prescription home use) falsely low INR test results, Class I Recall.
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRes/res.cfm?id=132045
FDA (2016) ROCKET-AF Re-Analysis reviews (Clinical, Statistical, Clinical Pharmacology Reviews). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202439Orig1s000RocketAFReanalysis.pdf (Accessed 15th June 2018)
Freidson, E. (1970) Profession of medicine: A study in the sociology of applied knowledge. Dodd Mead.
Gabe, J., & Bury, M. (1996) Halcion nights: A sociological account of a medical controversy. Sociology, 30(3), 447-469. https://doi.org/10.1177/0038038596030003003
Gabe, J., Chamberlain, K., Norris, P., Dew, K., Madden, H., & Hodgetts, D. (2012) The debate about the funding of Herceptin: A case study of ‘countervailing powers’. Social Science & Medicine, 75(12), 2353-2561. https://doi.org/10.1016/j.socscimed.2012.09.009
Gardner, J. (2016, March 17th) Johnson & Johnson, Bayer caught hiding data from product study — Leading to hundreds of deaths. The Free Thought Project Website. https://www.bibliotecapleyades.net/ciencia/ciencia_industrybigpharma183.htm (Accessed 2 March 2026)
Harris, L. F., Castro-Lopez, V., & Killard, A. J. (2013) Coagulation monitoring devices: Past, present and future at the point of care. TrAC Trends in Analytical Chemistry, 50, 85-95. https://doi.org/10.1016/j.trac.2013.05.009
Hogarth, S., & Martin, P. (2021) The ratio of vision to data: Promoting emergent science and technologies through promissory regulation, the case of FDA and personalized medicine. Regulation & Governance, 15(3) , 969-986. https://doi.org/10.1111/rego.12360
Hogarth, S., Miller, F. A., & Sturdy, S. (2022) Multidisciplinary perspectives on regulation of diagnostic technologies. Social Science & Medicine, 304, 115059. https://doi.org/10.1016/j.socscimed.2022.115059
Johnson & Johnson (2025) 2024 annual report. https://www.jnj.com/download/johnson-johnson-2024-annual-report
Kingori, P. (2015) The ‘empty choice’: A sociological examination of choosing medical research participation in resource-limited Sub-Saharan Africa. Current Sociology, 63(5), 763-778. https://doi.org/10.1177/0011392115590093
Larson, M. S. (1977) The rise of professionalism: A sociological analysis. University of California Press.
Light, D. W. (1991) Professionalism as a countervailing power. Journal of Health Politics, Policy and Law, 16(3), 499-506. https://doi.org/10.1215/03616878-16-3-499
Light, D. W. (2010) Health-care professions, markets and countervailing powers. In C. E. Bird et al. (Eds.), Handbook of medical sociology (pp. 270-89). Vanderbilt University Press.
Maggetti, M., Ewert, C., & Trein, P. (2017) Not quite the same: Regulatory intermediaries in the governance of pharmaceuticals and medical devices. The ANNALS of the American Academy of Political and Social Science, 670(1), 152-169. https://doi.org/10.1177/0002716217691240
Mahase, E. (2023) NHS England drive sees almost half a million people started on anticoagulant drugs. BMJ, 383, 2567. https://doi.org/10.1136/bmj.p2567
Main, B., & Ozieranski, P. (2021) Divergent spender: State-societal and meso-organisational mechanisms in the containment of public spending on pharmaceuticals in a liberal capitalist democracy. Sociology of Health & Illness, 43(6),1518-1539. https://doi.org/10.1111/1467-9566.13343
Mbroh, J., Birschmann, I., Ebner, M., Kremer Hovinga J. A., Lindhoff-Last, E., Purrucker, J., …& Poli, S. (2025) Rapid assessment of direct oral anticoagulants in acute stroke — An educational systematic review. European Stroke Journal. 10 (1_suppl), 24-34. doi:10.1177/23969873241310359
McKinlay, J. B. (1981) From promising report to standard procedure: Seven stages in the career of a medical innovation. Milbank Memorial Fund Quarterly, 59(3), 374-411. https://www.milbank.org/wp-content/uploads/mq/volume-59/issue-03/59-3-Promising-Report-to-Standard-Procedure.pdf
McLaren, L., Green, J., & Labonte, R. (2025) New directions in critical public health: Health in turbulent times. Routledge. https://doi.org/10.4324/9781003654650
McNulty, R. (2024, Sept 12th) New estimates suggest atrial fibrillation 3 times more common than thought. AJMC. https://www.ajmc.com/view/new-estimates-suggest-atrial-fibrillation-3-times-more-common-than-thought (Accessed 2 March 2026)e
Meier, B. (2011, Feb 14th) Recalled devices mostly untested, new study says. The New York Times. https://stopcancerfund.org/in-the-news/were-in-the-news/news-stories-editorials/recalled-devices-mostly-untested-new-study-says/ (Accessed 26 July 2016)
MHRA (2026a) Total report file for rivaroxaban. Reports by year. https://yellowcard.mhra.gov.uk/idaps/RIVAROXABAN (Accessed 3 March 2026)
MHRA (2026b) Total report file for warfarin. Reports by year. https://yellowcard.mhra.gov.uk/idaps/WARFARIN (Accessed 3 March 2026)
Molteni, M., Friz, H. P., Primitz, L., Marano, G., Boracchi, P., & Cimminiello, C. (2014) The definition of valvular and non-valvular atrial fibrillation: Results of a physicians’ survey. EP Europace. 16(12), 1720-1725. https://doi.org/10.1093/europace/euu178
Moore, D., Fraser, S., Farrugia, A., Fomiatti, R., Edwards, M., Birbilis, E., & Treloar, C. (2024) Countering ‘the moral science of biopolitics’: Understanding hepatitis C treatment ‘non-compliance’ in the antiviral era. Sociology of Health & Illness, 46(3), 399-417. https://doi.org/10.1111/1467-9566.13712
NHS England (2019) Prescription cost analysis - England 2018 [PAS]. ONS. https://digital.nhs.uk/data-and-information/publications/statistical/prescription-cost-analysis/2018
NICE (2004) Guide to the methods of technology appraisal. NICE. https://assets.publishing.service.gov.uk/media/5a7a5acee5274a34770e6144/NICE_guide_to_the_methods_of_technology_appraisal.pdf (Accessed 15 June 2020)
NICE (2012) Technology-appraisal guidance TA256; Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation. NICE. https://www.nice.org.uk/guidance/ta256/resources/rivaroxaban-for-the-prevention-of-stroke-and-systemic-embolism-in-people-with-atrial-fibrillation-pdf-82600494885061
NICE (2014a, Sept 24th) Diagnostics Guidance DG14: Atrial fibrillation and heart valve disease: self-monitoring coagulation status using point-of-care coagulometers (CoaguChek XS system and INRatio2 PT/INR monitor). NICE.
NICE (2014b) Atrial fibrillation: The management of atrial fibrillation (the full guideline), clinical guideline methods, evidence and recommendations. National Clinical Guideline Centre, https://webarchive.nationalarchives.gov.uk/ukgwa/20150505092248mp_/http://www.nice.org.uk/guidance/cg180/evidence/cg180-atrial-fibrillation-update-full-guideline3
NICE (2014c, June 18th) Clinical Guideline CG180 (short version). The management of atrial fibrillation: The Guideline Development Group, National Clinical Guideline Centre and NICE Project Team. https://www.nice.org.uk/Guidance/Cg180/Chapter/4-The-Guideline-Development-Group-National-Clinical-Guideline-Centre-And-Nice-Project-Team
NICE (2018) Updated Diagnostic Guidance DG14: Atrial fibrillation and heart valve disease: Self-monitoring coagulation status using point-of-care coagulometers (CoaguChek XS system). [September 2014]. Last updated: December 2017. https://www.nice.org.uk/guidance/dg14 (Accessed 6 July 2020)
NICE (2025) Making decisions using NICE guidelines. NICE. https://www.nice.org.uk/what-nice-does/our-guidance/about-nice-guidelines/making-decisions-using-nice-guidelines (Accessed 2 March 2026)
Office of Public Affairs (2021, July 8th) Medical device companies Alere Inc. and Alere San Diego Inc. agree to pay $38.75 million to settle False Claims Act allegations. Press Release. US Department of Justice. https://www.justice.gov/archives/opa/pr/medical-device-companies-alere-inc-and-alere-san-diego-inc-agree-pay-3875-million-settle (Accessed 24 August 2025)
Orlowski, A., Gale, C. P., Ashton, R., Petrungaro, B., Slater, R., Nadarajah, R., ... & Wu, J. (2021) Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation. Heart, 107(1), 47-53. https://doi.org/10.1136/heartjnl-2020-317006
Ozieranski, P., Pitter, J., Rickard, E. Mulinari, S., & Csanadi, M. (2022) A ‘patient-industry complex’: Investigating financial dependency of UK patient organizations on drug company funding. Sociology of Health & Illness, 44(1), 188–210. https://doi.org/10.1111/1467-9566.13409
Patel, M. R., Mahaffey, K. W., Garg, J., Pan, G., Singer, D. E., Hacke, W., ... & AF Steering Committee (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New England Journal of Medicine, 365(10), 883-891. doi:10.1056/NEJMoa1009638
Patel, M. R., Hellkamp, A. S., & Fox, K. A. A. (2016a) Point-of-care warfarin monitoring in the ROCKET AF trial. New England Journal of Medicine, 374(8), 785-788. doi: 10.1056/NEJMc1515842
Patel, M. R., Hellkamp, A. S., & Fox, K. A. A. (2016b) Point-of-care warfarin monitoring in the ROCKET AF trial - Reply to Powell New England Journal of Medicine, 375(4), 390-91. doi: 10.1056/NEJMc1604020
Pfizer (2024) Annual review 2024. https://annualreview.pfizer.com (Accessed 3 March 2026)
Powell, R. (2016) Point-of-care warfarin monitoring in the ROCKET AF trial. New England Journal of Medicine, 375(4): 390-391. doi: 10.1056/NEJMc1604020
Rosengarten, M., & Savransky, M. (2019) A careful biomedicine? Generalization and abstraction in RCTs. Critical Public Health, 29(2), 181-191. https://doi.org/10.1080/09581596.2018.1431387
Ross, S., Robert, M., & Ducey, A. (2015) The short life-cycle of a surgical device. Health Policy and Technology, 4(2), 168-188. https://doi.org/10.1016/j.hlpt.2015.02.008
Sandberg, B. (2018, April 28th) Strong Xarelto label warnings lead to another jury win for Bayer and Janssen. Pink Sheet. https://insights.citeline.com/PS122996/Strong-Xarelto-Label-Warnings-Lead-To-Another-Jury-Win-For-Bayer-And-Janssen/ (Accessed 25 August 2025)
Sandberg, B. (2019, March 26th) After five-year winning streak, Xarelto-makers settle personal injury suits. Pink Sheet. https://insights.citeline.com/PS124988/After-5Year-Winning-Streak-Xarelto-Makers-Settle-Personal-Injury-Suits/ (Accessed 25 August 2025)
Shoveller, J., Viehbeck, S., Di Ruggiero, E., Greyson, D., Thomson, K., & Knight, R. (2016) A critical examination of representations of context within research on population health interventions. Critical Public Health, 26(5), 487-500. https://doi.org/10.1080/09581596.2015.1117577
Stovall, S. (2015, Dec 11th) Bayer brushes off Xarelto study device defect worries. Scrip: Commercial News & Insights. https://insights.citeline.com/SC063947/Bayer-Brushes-Off-Xarelto-Study-Device-Defect-Worries/ (Accessed 25 August 2025)
Stroke Association (2024) Atrial fibrillation (AF) and stroke. https://www.stroke.org.uk/atrial_fibrillation_and_stroke_guide.pdf (Accessed 2nd March 2026)
Sutter, S. (2016, Oct 11th) FDA lifts clouds over J&J’s Xarelto with ROCKET-AF re-analysis. Pink Sheet. https://insights.citeline.com/PS119301/FDA-Lifts-Cloud-Over-JampJs-Xarelto-With-ROCKETAF-ReAnalysis/ (Accessed 25 August 2025)
Thomas, K. (2016, March 2nd) Document claims drug-makers deceived a top medical journal. The New York Times. https://www.nytimes.com/2016/03/02/business/document-claims-drug-makers-deceived-a-top-medical-journal.html (Accessed 26 July 2016)
Verified Market Research (2026) Point-of-care coagulation testing devices market. https://www.verifiedmarketresearch.com/product/point-of-care-coagulation-testing-devices-market/ (Accessed 2 March 2026)
Wall, L. L., & Brown, D. (2010) The perils of commercially-driven surgical innovation. American Journal of Obstetrics & Gynecology, 202, e1-e30. https://doi.org/10.1016/j.ajog.2009.05.031
Woolcock, M. (2013) Using case studies to explore the external validity of ‘complex’ development interventions. Evaluation, 19(3), 229-248. https://doi.org/10.1177/1356389013495210
Zuckerman, D. M., Brown, P., & Nissen, S.E. (2011) Medical device recalls and the FDA Approval process. Archives of Internal Medicine, 171(11), 1006-1011.
Published
Issue
Section
License
Copyright (c) 2025 Gowree Balendran, John Abraham
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
All articles in the Journal of Critical Public Health are published under a CC-BY-NC-ND license, or a CC-BY license if authors or their funders require this. The default CC-BY-NC-ND license means that authors and users may copy and distribute the material in any medium or format in un-adapted form only, for non-commercial purposes only, and only so long as proper credit is given (as is customary in academic work). Authors retain copyright of their work published in Journal of Critical Public Health and full publishing rights without restrictions
