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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Reviewing the Mechanistic Evidence Assessors E-Synthesis and EBM+: A Case Study of Amoxicillin and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Author(s): Ahmad Y. Abdin, Daniel Auker-Howlett, Jürgen Landes, Glorjen Mulla, Claus Jacob and Barbara Osimani*

Volume 25, Issue 16, 2019

Page: [1866 - 1880] Pages: 15

DOI: 10.2174/1381612825666190628160603

Price: $65

Abstract

Background: Basic science has delivered unprecedented insights into intricate relationships on the smallest scales within well-controlled environments. Addressing pressing societal decision problems requires an understanding of systems on larger scales in real-world situations.

Objective: To assess how well the evidence assessors E-Synthesis and EBM+ assess basic science findings to support medical decision making.

Methods: We demonstrate the workings of E-Synthesis and EBM+ on a case study: the suspected causal connection between the widely-used drug amoxicillin (AMX) and the putative adverse drug reaction: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Results: We determine an increase in the probability that AMX can cause DRESS within the E-Synthesis approach and using the EBM+ standards assess the basic science findings as supporting the existence of a mechanism linking AMX and DRESS.

Conclusions: While progress is made towards developing methodologies which allow the incorporation of basic science research in the decision making process for pressing societal questions, there is still considerable need for further developments. A continued dialogue between basic science researchers and methodologists, philosophers and statisticians seems to offer the best prospects for developing and evaluating continuously evolving methodologies.

Keywords: Evidence aggregation, E-synthesis, EBM+, amoxicillin, DRESS, drug safety, adverse drug reactions, pharmacovigilance, drug monitoring, pharmacosurveillance, bradford hill guidelines, causal inference.

[1]
Landes J, Osimani B, Poellinger R. Epistemology of causal inference in pharmacology. Eur J Philos Sci 2018; 8: 3-49.
[http://dx.doi.org/10.1007/s13194-017-0169-1]
[2]
Landes J, Osimani B. E-Synthesis: a bayesian framework for causal assessment in pharmacosurveillance. Front Pharmacolunder review 2019.
[3]
Parkkinen VP, Wallmann C, Wilde M, Clarke B, Illari P, Kelly MP, et al. Evaluating evidence of mechanisms in medicine: Principles and procedures. Springer 2018.
[http://dx.doi.org/10.1007/978-3-319-94610-8]
[4]
European Medicines Agency. PRAC recommendations on signals 3-6 July 2017 2017. July 3-6.
[5]
Osimani B, Mignini F. Causal assessment of pharmaceutical treatments: why standards of evidence should not be the same for benefits and harms? Drug Saf 2015; 38(1): 1-11.
[http://dx.doi.org/10.1007/s40264-014-0249-5] [PMID: 25519721]
[6]
Osimani B. Probabilistic information and decision making in the health context: The package leaflet as basis for informed consent Lugano: Università della Svizzera italiana. 2007.
[7]
Osimani B. Hunting side effects and explaining them: Should we reverse evidence hierarchies upside down? Topoi (Dordr) 2014; 33(2): 295-312.
[http://dx.doi.org/10.1007/s11245-013-9194-7]
[8]
Edwards IR. Good pharmacovigilance practice and the curate’s egg. Drug Saf 2012; 35(6): 429-35.
[http://dx.doi.org/10.2165/11634410-000000000-00000] [PMID: 22612849]
[9]
Vandenbroucke JP. Observational research, randomised trials, and two views of medical science. PLoS Med 2008; 5(3)e67
[http://dx.doi.org/10.1371/journal.pmed.0050067] [PMID: 18336067]
[10]
Vandenbroucke JP, Psaty BM. Benefits and risks of drug treatments: how to combine the best evidence on benefits with the best data about adverse effects. JAMA 2008; 300(20): 2417-9.
[http://dx.doi.org/10.1001/jama.2008.723] [PMID: 19033592]
[11]
Cooper N, Coyle D, Abrams K, Mugford M, Sutton A. Use of evidence in decision models: an appraisal of health technology assessments in the UK since 1997. J Health Serv Res Policy 2005; 10(4): 245-50.
[http://dx.doi.org/10.1258/135581905774414187] [PMID: 16259692]
[12]
Herxheimer A. Pharmacovigilance on the turn? Adverse reactions methods in 2012. Br J Gen Pract 2012; 62(601): 400-1.
[http://dx.doi.org/10.3399/bjgp12X653453] [PMID: 22867653]
[13]
Beasley CM, Dellva MA, Tamura RN, et al. Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol. Br J Psychiatry 1999; 174: 23-30.
[http://dx.doi.org/10.1192/bjp.174.1.23] [PMID: 10211147]
[14]
Food and Drug Administration Drug Induced Liver Injury: Premarketing Clinical Evaluation - Guidance for Industry 2009.http://www.fda.gov/downloads/Drugs/Guidance/UCM174090.pdf
[15]
Onakpoya IJ, Heneghan CJ, Aronson JK. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis. Crit Rev Toxicol 2016; 46(6): 477-89.
[http://dx.doi.org/10.3109/10408444.2016.1149452] [PMID: 26941185]
[16]
WHO Model List of Essential Medicines. 20th ed. 2017.
[17]
Kaur SP, Rao R, Nanda S. Amoxicillin: a broad spectrum antibiotic. Int J Pharm Pharm Sci 2011; 3: 30-7.
[18]
Ariza A, Mayorga C, Fernández TD, et al. Hypersensitivity reactions to β-lactams: relevance of hapten-protein conjugates. J Investig Allergol Clin Immunol 2015; 25(1): 12-25.
[PMID: 25898690]
[19]
Pichichero ME, Zagursky R. Penicillin and cephalosporin allergy. Ann Allergy Asthma Immunol 2014; 112(5): 404-12.
[http://dx.doi.org/10.1016/j.anai.2014.02.005] [PMID: 24767695]
[20]
Lafaye P, Lapresle C. Fixation of penicilloyl groups to albumin and appearance of anti-penicilloyl antibodies in penicillin-treated patients. J Clin Invest 1988; 82(1): 7-12.
[http://dx.doi.org/10.1172/JCI113603] [PMID: 3392217]
[21]
Rolinson GN. 6-APA and the development of the beta-lactam antibiotics. J Antimicrob Chemother 1979; 5(1): 7-14.
[http://dx.doi.org/10.1093/jac/5.1.7] [PMID: 216660]
[22]
Prescriptions Dispensed in the Community - Statistics for England, 2002-2012. National Health Service 2013.
[23]
Centres for Disease Control and Prevention Outpatient antibiotic prescriptions - United States 2015.https://www.cdc.gov/antibiotic-use/community/pdfs/Annual-Report-2015.pdf
[24]
Diagnosis and management of acute otitis media. Pediatrics 2004; 113(5): 1451-65.
[http://dx.doi.org/10.1542/peds.113.5.1451] [PMID: 15121972]
[25]
Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology: Elsevier Health Sciences. 2016.
[26]
Criado PR, Avancini J, Santi CG, Medrado ATA, Rodrigues CE, de Carvalho JF. Drug reaction with eosinophilia and systemic symptoms (DRESS): a complex interaction of drugs, viruses and the immune system. Isr Med Assoc J 2012; 14(9): 577-82.
[PMID: 23101424]
[27]
Demoly P, Adkinson NF, Brockow K, et al. International Consensus on drug allergy. Allergy 2014; 69(4): 420-37.
[http://dx.doi.org/10.1111/all.12350] [PMID: 24697291]
[28]
Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 2006; 55(1): 1-8.
[http://dx.doi.org/10.2332/allergolint.55.1] [PMID: 17075280]
[29]
Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol 2013; 169(5): 1071-80.
[http://dx.doi.org/10.1111/bjd.12501] [PMID: 23855313]
[30]
Fang WC, Adler NR, Graudins LV, et al. Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions: experience from two Australian tertiary hospitals. Intern Med J 2018; 48(5): 549-55.
[http://dx.doi.org/10.1111/imj.13734] [PMID: 29316113]
[31]
Britschgi M, von Greyerz S, Burkhart C, Pichler WJ. Molecular aspects of drug recognition by specific T cells. Curr Drug Targets 2003; 4(1): 1-11.
[http://dx.doi.org/10.2174/1389450033347082] [PMID: 12528985]
[32]
Pichler WJ, Adam J, Watkins S, Wuillemin N, Yun J, Yerly D. Drug hypersensitivity: How drugs stimulate t cells via pharmacological interaction with immune receptors. Int Arch Allergy Immunol 2015; 168(1): 13-24.
[http://dx.doi.org/10.1159/000441280] [PMID: 26524432]
[33]
Wuillemin N, Adam J, Fontana S, Krähenbühl S, Pichler WJ, Yerly D. HLA haplotype determines hapten or p-i T cell reactivity to flucloxacillin. J Immunol 2013; 190(10): 4956-64.
[http://dx.doi.org/10.4049/jimmunol.1202949] [PMID: 23596311]
[34]
Carey MA, van Pelt FN. Immunochemical detection of flucloxacillin adduct formation in livers of treated rats. Toxicology 2005; 216(1): 41-8.
[http://dx.doi.org/10.1016/j.tox.2005.07.015] [PMID: 16112790]
[35]
Norcross MA, Luo S, Lu L, et al. Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity. AIDS 2012; 26(11): F21-9.
[http://dx.doi.org/10.1097/QAD.0b013e328355fe8f] [PMID: 22617051]
[36]
Meng X, Lawrenson AS, Berry NG, et al. Abacavir forms novel cross-linking abacavir protein adducts in patients. Chem Res Toxicol 2014; 27(4): 524-35.
[http://dx.doi.org/10.1021/tx400406p] [PMID: 24571427]
[37]
Ariza A, Garzon D, Abánades DR, et al. Protein haptenation by amoxicillin: high resolution mass spectrometry analysis and identification of target proteins in serum. J Proteomics 2012; 77: 504-20.
[http://dx.doi.org/10.1016/j.jprot.2012.09.030] [PMID: 23041134]
[38]
Garzon D, Ariza A, Regazzoni L, et al. Mass spectrometric strategies for the identification and characterization of human serum albumin covalently adducted by amoxicillin: ex vivo studies. Chem Res Toxicol 2014; 27(9): 1566-74.
[http://dx.doi.org/10.1021/tx500210e] [PMID: 25088930]
[39]
Hautekeete ML, Horsmans Y, Van Waeyenberge C, et al. HLA association of amoxicillin-clavulanate--induced hepatitis. Gastroenterology 1999; 117(5): 1181-6.
[http://dx.doi.org/10.1016/S0016-5085(99)70404-X] [PMID: 10535882]
[40]
Hill AB. The Environment and Disease: Association or Causation? Proc R Soc Med 1965; 58: 295-300.
[PMID: 14283879]
[41]
Hawthorne J. Degree-of-Belief and Degree-of-Support: Why Bayesians Need Both Notions. Mind 2005; 114(454): 277-320.
[http://dx.doi.org/10.1093/mind/fzi277]
[42]
Ioannidis JPA. Exposure-wide epidemiology: revisiting Bradford Hill. Stat Med 2016; 35(11): 1749-62.
[http://dx.doi.org/10.1002/sim.6825] [PMID: 26646432]
[43]
Howick J, Glasziou P, Aronson JK. The evolution of evidence hierarchies: what can Bradford Hill’s ‘guidelines for causation’ contribute? J R Soc Med 2009; 102(5): 186-94.
[http://dx.doi.org/10.1258/jrsm.2009.090020] [PMID: 19417051]
[44]
Fedak KM, Bernal A, Capshaw ZA, Gross S. Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology. Emerg Themes Epidemiol 2015; 12: 14.
[http://dx.doi.org/10.1186/s12982-015-0037-4] [PMID: 26425136]
[45]
Höfler M. The Bradford Hill considerations on causality: a counterfactual perspective. Emerg Themes Epidemiol 2005; 2: 11.
[http://dx.doi.org/10.1186/1742-7622-2-11] [PMID: 16269083]
[46]
Perrio M, Voss S, Shakir SAW. Application of the bradford hill criteria to assess the causality of cisapride-induced arrhythmia: a model for assessing causal association in pharmacovigilance. Drug Saf 2007; 30(4): 333-46.
[http://dx.doi.org/10.2165/00002018-200730040-00006] [PMID: 17408310]
[47]
Bovens L, Hartmann S. Bayesian Epistemology. Oxford University Press 2003.
[48]
Talbott W. Bayesian Epistemology. In Zalta EN, editor The Stanford Encyclopedia of Philosophy 2011th ed. 2011.
[49]
Howson C, Urbach P. Scientific Reasoning. 3rd ed. Chicago and La Salle: Open Court;. 2006.
[50]
Gelman A, Hennig C. Beyond subjective and objective in statistics. J R Stat Soc Ser A Stat Soc 2017; 180: 967-1033.
[http://dx.doi.org/10.1111/rssa.12276]
[51]
Sprenger J. The objectivity of Subjective Bayesianism. Eur J Philos Sci 2018.
[http://dx.doi.org/10.1007/s13194-018-0200-1]
[52]
Darwiche A. Modeling and reasoning with Bayesian networks. Cambridge University Press 2009.
[http://dx.doi.org/10.1017/CBO9780511811357]
[53]
Neapolitan RE. Learning Bayesian Networks. Pearson 2003.
[54]
Bogen J, Woodward J. Saving the Phenomena. Philos Rev 1988; 97: 303.
[http://dx.doi.org/10.2307/2185445]
[55]
Pichler WJ. Consequences of drug binding to immune receptors: Immune stimulation following pharmacological interaction with immune receptors (T-cell receptor for antigen or human leukocyte antigen) with altered peptide-human leukocyte antigen or peptide. Zhonghua Pifuke Yixue Zazhi 2013; 31: 181-90.
[http://dx.doi.org/10.1016/j.dsi.2013.09.005]
[56]
Gancheva T, Gancheva D, Troeva Z, Velev V, Hristakieva E, Tsokeva Z, et al. Carbamazepine-induced DRESS syndrome: A case report. J Pharmacol Clin Toxicol 2017; 5.
[57]
Markel A. Allopurinol-induced DRESS syndrome. Isr Med Assoc J 2005; 7(10): 656-60.
[PMID: 16259349]
[58]
Dardashti R, Hartmann S, Thebault KPY, Winsberg E. Hawking Radiation and Analogue Experiments. Studies in History and Philosophy of Modern Physics 2019.
[http://dx.doi.org/10.1016/j.shpsb.2019.04.004]
[59]
Howick J. The Philosophy of Evidence-Based Medicine Wiley-Blackwell. 2011.Studies in History and Philosophy of Modern Physics.
[60]
Russo F, Williamson J. Interpreting Causality in the Health Sciences. Int Stud Philos Sci 2007; 21: 157-70.
[http://dx.doi.org/10.1080/02698590701498084]
[61]
Williamson J. Establishing causal claims in medicine. Int Stud Philos Sci 2019; 1-30.
[http://dx.doi.org/10.1080/02698595.2019.1630927]
[62]
Clarke B, Gillies D, Illari P, Russo F, Williamson J. Mechanisms and the Evidence Hierarchy. Topoi (Dordr) 2014; 33(2): 339-60.
[http://dx.doi.org/10.1007/s11245-013-9220-9]
[63]
Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: A new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol 2011; 64(4): 380-2.
[http://dx.doi.org/10.1016/j.jclinepi.2010.09.011] [PMID: 21185693]
[64]
Ariza A, Collado D, Vida Y, et al. Study of protein haptenation by amoxicillin through the use of a biotinylated antibiotic. PLoS One 2014; 9(3)e90891
[http://dx.doi.org/10.1371/journal.pone.0090891] [PMID: 24595455]
[65]
Elschenbroich S, Kislinger T. Targeted proteomics by selected reaction monitoring mass spectrometry: applications to systems biology and biomarker discovery. Mol Biosyst 2011; 7(2): 292-303.
[http://dx.doi.org/10.1039/C0MB00159G] [PMID: 20976349]
[66]
O’Donohue J, Oien KA, Donaldson P, et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut 2000; 47(5): 717-20.
[http://dx.doi.org/10.1136/gut.47.5.717] [PMID: 11034591]
[67]
Lucena MI, Molokhia M, Shen Y, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology 2011; 141(1): 338-47.
[http://dx.doi.org/10.1053/j.gastro.2011.04.001] [PMID: 21570397]
[68]
Daly AK, Donaldson PT, Bhatnagar P, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009; 41(7): 816-9.
[http://dx.doi.org/10.1038/ng.379] [PMID: 19483685]
[69]
La Caze A. Osimani B Uncertainty in Pharmacology: Epistemology, Methods, and Decisions' to 'in La Caze A, Osimani B (eds.) Uncertainty in Pharmacology: Epistemology, Methods, and Decisions. Amsterdam: Springer 2019; 50-62.
[70]
Laubender RP, Mansmann U. Estimating individual treatment effects from responses and a predictive biomarker in a parallel group RCT. Technical Report Munich: Ludwig-Maximilians Universität, Department of Statistics; 2014. Report No.: 176.
[71]
Colombo M, Gervais R, Sprenger J. Introduction: objectivity in science. Synthese 2017; 194: 4641-2.
[http://dx.doi.org/10.1007/s11229-017-1582-x]
[72]
Tricco AC, Soobiah C, Antony J, et al. A scoping review identifies multiple emerging knowledge synthesis methods, but few studies operationalize the method. J Clin Epidemiol 2016; 73: 19-28.
[http://dx.doi.org/10.1016/j.jclinepi.2015.08.030] [PMID: 26891949]
[73]
Linkov I, Loney D, Cormier S, Satterstrom FK, Bridges T. Weight-of-evidence evaluation in environmental assessment: review of qualitative and quantitative approaches. Sci Total Environ 2009; 407(19): 5199-205.
[http://dx.doi.org/10.1016/j.scitotenv.2009.05.004] [PMID: 19619890]
[74]
Kastner M, Antony J, Soobiah C, Straus SE, Tricco AC. Conceptual recommendations for selecting the most appropriate knowledge synthesis method to answer research questions related to complex evidence. J Clin Epidemiol 2016; 73: 43-9.
[http://dx.doi.org/10.1016/j.jclinepi.2015.11.022] [PMID: 26912124]
[75]
Handbook for conducting a literature-based health assessment 276 using OHAT approach for systemic review and evidence integration. 2015; 1-98.
[76]
Morgan RL, Thayer KA, Bero L, et al. GRADE: Assessing the quality of evidence in environmental and occupational health. Environ Int 2016; 92-93: 611-6.
[http://dx.doi.org/10.1016/j.envint.2016.01.004] [PMID: 26827182]
[77]
Mercuri M, Baigrie B, Upshur REG. Going from evidence to recommendations: Can GRADE get us there? J Eval Clin Pract 2017; 2018: 1-8.
[http://dx.doi.org/10.1111/jep.12857] [PMID: 29314554]
[78]
Vieland VJ, Chang H. No evidence amalgamation without evidence measurement. Synthese 2018.
[http://dx.doi.org/10.1007/s11229-017-1666-7]
[79]
Broadbent A, Vandenbroucke JP, Pearce N. Response: Formalism or pluralism? A reply to commentaries on ‘Causality and causal inference in epidemiology’. Int J Epidemiol 2016; 45(6): 1841-51.
[http://dx.doi.org/10.1093/ije/dyw298] [PMID: 28130316]
[80]
Beisbart C. Are computer simulations experiments? And if not, how are they related to each other? Eur J Philos Sci 2017; 8(2): 171-204.
[http://dx.doi.org/10.1007/s13194-017-0181-5]
[81]
Osimani B, Bertolaso M, Poellinger R, Frontoni E. Real and Virtual Clinical Trials: A Formal Analysis. Topoi (Dordr) 2019.
[http://dx.doi.org/10.1007/s11245-018-9563-3]
[82]
Pearl J. Causality Models, Reasoning and Inference. 2nd ed. Cambridge: Cambridge University Press 2009.
[http://dx.doi.org/10.1017/CBO9780511803161]
[83]
Salmon W. Scientific Explanation and the Causal Structure of the World Princeton. Princeton University Press 1984.
[84]
Glennan S. The New Mechanical Philosophy. Oxford University Press 2017.
[http://dx.doi.org/10.1093/oso/9780198779711.001.0001]

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