Methods to Compare Adverse Events in Twitter to FAERS, Drug Information Databases, and Systematic Reviews: Proof of Concept with Adalimumab

IntroductionAdverse drug reactions (ADRs) are associated with significant health-related and financial burden, and multiple sources are currently utilized to actively discover them. Social media has been proposed as a potential resource for monitoring ADRs, but drug-specific analytical studies comparing social media with other sources are scarce.ObjectivesOur objective was to develop methods to compare ADRs mentioned in social media with those in traditional sources: the US FDA Adverse Event Reporting System (FAERS), drug information databases (DIDs), and systematic reviews.MethodsA total of 10,188 tweets mentioning adalimumab collected between June 2014 and August 2016 were included. ADRs in the corpus were extracted semi-automatically and manually mapped to standardized concepts in the Unified Medical Language System. ADRs were grouped into 16 biologic categories for comparisons. Frequencies, relative frequencies, disproportionality analyses, and rank ordering were used as metrics.ResultsThere was moderate agreement between ADRs in social media and traditional sources. “Local and injection site reactions” was the top ADR in Twitter, DIDs, and systematic reviews by frequency, ranked frequency, and index ranking. The next highest ADR in Twitter—fatigue—ranked fifth and seventh in FAERS and DIDs.ConclusionSocial media posts often express mild and symptomatic ADRs, but rates are measured differently in scientific sources. ADRs in FAERS are reported as absolute numbers, in DIDs as percentages, and in systematic reviews as percentages, risk ratios, or other metrics, which makes comparisons challenging; however, overlap is substantial. Social media analysis facilitates open-ended investigation of patient perspectives and may reveal concepts (e.g. anxiety) not available in traditional sources.

[1]  David W. Bates,et al.  The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group , 1997 .

[2]  Jonathan M. Teich,et al.  Identifying hospital admissions due to adverse drug events using a computer‐based monitor , 2001, AMIA.

[3]  D. Classen,et al.  Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. , 1997, JAMA.

[4]  D. Bates,et al.  The Costs of Adverse Drug Events in Hospitalized Patients , 1997 .

[5]  P. Corey,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 2012 .

[6]  M. Lindquist,et al.  A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions , 2002, Pharmacoepidemiology and drug safety.

[7]  M. Lindquist,et al.  A Data Mining Approach for Signal Detection and Analysis , 2002, Drug safety.

[8]  L. Leape.  Reporting of adverse events. , 2002, The New England journal of medicine.

[9]  Syed Rizwanuddin Ahmad,et al.  Adverse drug event monitoring at the food and drug administration , 2003, Journal of general internal medicine.

[10]  M. Hochberg,et al.  Comparison of the efficacy of the tumour necrosis factor α blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis , 2003, Annals of the rheumatic diseases.

[11]  J. Aronson,et al.  A comparison of three different sources of data in assessing the frequencies of adverse reactions to amiodarone. , 2004, British journal of clinical pharmacology.

[12]  M. Pirmohamed,et al.  Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients , 2004, BMJ : British Medical Journal.

[13]  N. Scheinfeld.  Adalimumab: a review of side effects , 2005, Expert opinion on drug safety.

[14]  C. Chiou,et al.  Review of Eight Pharmacoeconomic Studies of the Value of Biologic DMARDs Adalimumab, Etanercept, and Infliximab) in the Management of Rheumatoid Arthritis , 2006, Journal of managed care pharmacy : JMCP.

[15]  L. Hazell,et al.  Under-Reporting of Adverse Drug Reactions , 2006, Drug safety.

[16]  D. Pollock,et al.  National surveillance of emergency department visits for outpatient adverse drug events. , 2006, JAMA.

[17]  B. Hernández-Cruz,et al.  Adalimumab for treating rheumatoid arthritis. , 2005, The Journal of rheumatology.

[18]  C. Raehl,et al.  Adverse Drug Reactions in United States Hospitals , 2006, Pharmacotherapy.

[19]  P Barton,et al.  A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. , 2006, Health technology assessment.

[20]  H. Bliddal,et al.  The number needed to treat for adalimumab, etanercept, and infliximab based on ACR50 response in three randomized controlled trials on established rheumatoid arthritis: a systematic literature review , 2007, Scandinavian journal of rheumatology.

[21]  D. Vidt,et al.  Safety of Rosuvastatin: Update on 16,876 Rosuvastatin-Treated Patients in a Multinational Clinical Trial Program , 2007, Cardiology.

[22]  M. Kulldorff,et al.  Early detection of adverse drug events within population‐based health networks: application of sequential testing methods , 2007, Pharmacoepidemiology and drug safety.

[23]  T. J. Moore,et al.  Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. , 2007, Archives of internal medicine.

[24]  Tracy A. Lieu,et al.  Application of Information Technology: Using Electronic Medical Records to Enhance Detection and Reporting of Vaccine Adverse Events , 2007, J. Am. Medical Informatics Assoc..

[25]  T. Walley,et al.  Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. , 2007, Health technology assessment.

[26]  P. Noyce,et al.  Hospital Admissions Associated with Adverse Drug Reactions: A Systematic Review of Prospective Observational Studies , 2008, The Annals of pharmacotherapy.

[27]  P. Pillans.  Clinical perspectives in drug safety and adverse drug reactions , 2008, Expert review of clinical pharmacology.

[28]  D. Pollock,et al.  National surveillance of emergency department visits for outpatient adverse drug events in children and adolescents. , 2008, The Journal of pediatrics.

[29]  G. Kaplan,et al.  Systematic review: the short‐term and long‐term efficacy of adalimumab following discontinuation of infliximab , 2009, Alimentary pharmacology & therapeutics.

[30]  B. Dijkmans,et al.  Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases , 2009, Annals of the rheumatic diseases.

[31]  T. Einarson,et al.  The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events , 2008, Annals of the rheumatic diseases.

[32]  R. Pontarolo,et al.  A systematic review and meta-analysis of the efficacy and safety of adalimumab for treating rheumatoid arthritis , 2010, Rheumatology International.

[33]  Shivani Tanna,et al.  Improving reporting of adverse drug reactions: Systematic review , 2009, Clinical epidemiology.

[34]  R. Bell,et al.  Development of an online morbidity, mortality, and near-miss reporting system to identify patterns of adverse events in surgical patients. , 2009, Archives of surgery.

[35]  A. Bate,et al.  Quantitative signal detection using spontaneous ADR reporting , 2009, Pharmacoepidemiology and drug safety.

[36]  M. Ramos-Casals,et al.  Revisión sistemática del uso de adalimumab en enfermedades autoinmunes. Eficacia y seguridad en 54 pacientes , 2010 .

[37]  M. Ramos-Casals,et al.  Systematic review on the use of adalimumab in autoinmune. Efficacy and safety in 54 patients , 2010 .

[38]  Florence T. Bourgeois,et al.  Adverse drug events in the outpatient setting: an 11‐year national analysis , 2010, Pharmacoepidemiology and drug safety.

[39]  M. Connock,et al.  A systematic review and economic evaluation of the use of tumour necrosis factor-alpha (TNF-α) inhibitors, adalimumab and infliximab, for Crohn's disease. , 2011, Health technology assessment.

[40]  L. Peyrin-Biroulet,et al.  Loss of Response and Need for Adalimumab Dose Intensification in Crohn's Disease: A Systematic Review , 2011, The American Journal of Gastroenterology.

[41]  D. Symmons,et al.  Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta‐analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data , 2011, Pharmacoepidemiology and drug safety.

[42]  Xiao Bo Li,et al.  Efficacy and safety of adalimumab in Crohn's disease: Meta‐analysis of placebo‐controlled trials , 2011, Journal of digestive diseases.

[43]  B. Strober,et al.  The Long-Term Safety of Adalimumab Treatment in Moderate to Severe Psoriasis , 2011, American journal of clinical dermatology.

[44]  D. Spiegelhalter,et al.  Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis: a systematic review and economic evaluation. , 2011, Health technology assessment.

[45]  Janet Woodcock,et al.  Role of postmarketing surveillance in contemporary medicine. , 2011, Annual review of medicine.

[46]  P Barton,et al.  Adalimumab, etanercept, infliximab, rituximab and abatacept for the treatment of rheumatoid arthritis after the failure of a tumour necrosis factor inhibitor: a systematic review and economic evaluation. , 2011, Health technology assessment.

[47]  Susan J. Forray,et al.  National burden of preventable adverse drug events associated with inpatient injectable medications: healthcare and medical professional liability costs. , 2012, American health & drug benefits.

[48]  H. Bliddal,et al.  Efficacy of treatment intensification with adalimumab, etanercept and infliximab in rheumatoid arthritis: a systematic review of cohort studies with focus on dose. , 2013, Seminars in arthritis and rheumatism.

[49]  Clinical and Epidemiological Research , .

[50]  Jinshui Zhu,et al.  Adalimumab for Crohn’s disease after infliximab treatment failure: a systematic review , 2013, European journal of gastroenterology & hepatology.

[51]  Guidance for Industry and FDA Staff Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data , 2013 .

[52]  N. Shah,et al.  Performance of Pharmacovigilance Signal‐Detection Algorithms for the FDA Adverse Event Reporting System , 2013, Clinical pharmacology and therapeutics.

[53]  P. Kawalec,et al.  Tumor necrosis factor-α antibodies (infliximab, adalimumab and certolizumab) in Crohn's disease: systematic review and meta-analysis , 2013, Archives of medical science : AMS.

[54]  Juliana de Oliveira Costa,et al.  Adalimumab in rheumatoid arthritis treatment: a systematic review and meta-analysis of randomized clinical trials. , 2013, Revista brasileira de reumatologia.

[55]  S. Fénix-Caballero,et al.  Direct and indirect comparison of the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in psoriatic arthritis , 2013, Journal of clinical pharmacy and therapeutics.

[56]  A. Bitton,et al.  Adalimumab monotherapy versus combination therapy with immunomodulators in patients with Crohn's disease: a systematic review and meta-analysis. , 2014, Journal of Crohn's & colitis.

[57]  Junhua Xiao,et al.  Efficacy and safety of adalimumab for the Crohn’s disease: a systematic review and meta-analysis of published randomized placebo-controlled trials , 2014, European Journal of Clinical Pharmacology.

[58]  Taha A. Kass-Hout,et al.  Digital Drug Safety Surveillance: Monitoring Pharmaceutical Products in Twitter , 2014, Drug Safety.

[59]  K. Thorlund,et al.  Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naïve to anti-TNF therapy: an indirect treatment comparison meta-analysis. , 2014, Journal of Crohn's & colitis.

[60]  L. Peyrin-Biroulet,et al.  Pharmacokinetics of Adalimumab in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis , 2014, Inflammatory bowel diseases.

[61]  D. Zuo,et al.  Randomized, placebo controlled and double‐blind trials of efficacy and safety of adalimumab for treating ankylosing spondylitis: a meta‐analysis , 2014, International journal of rheumatic diseases.

[62]  Graciela Gonzalez-Hernandez,et al.  Pharmacovigilance on Twitter? Mining Tweets for Adverse Drug Reactions , 2014, AMIA.

[63]  Rolf Wynn,et al.  The clinical case report: a review of its merits and limitations , 2014, BMC Research Notes.

[64]  Graciela Gonzalez,et al.  Phonetic Spelling Filter for Keyword Selection in Drug Mention Mining from Social Media , 2014, AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science.

[65]  J. Montastruc,et al.  Undesirable Effects Related to Oral Antineoplastic Drugs: Comparison Between Patients’ Internet Narratives and a National Pharmacovigilance Database , 2014, Drug Safety.

[66]  Abeed Sarker,et al.  Portable automatic text classification for adverse drug reaction detection via multi-corpus training , 2015, J. Biomed. Informatics.

[67]  A. Burgun,et al.  Adverse Drug Reaction Identification and Extraction in Social Media: A Scoping Review , 2015, Journal of medical Internet research.

[68]  Graciela Gonzalez-Hernandez,et al.  Utilizing social media data for pharmacovigilance: A review , 2015, J. Biomed. Informatics.

[69]  S. Golder,et al.  Systematic review on the prevalence, frequency and comparative value of adverse events data in social media. , 2015, British journal of clinical pharmacology.

[70]  K. Thorlund,et al.  Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs , 2015, Expert review of gastroenterology & hepatology.

[71]  Ying Zou,et al.  Short-term effect and adverse events of adalimumab versus placebo in inducing remission for moderate-to-severe ulcerative colitis: a meta-analysis. , 2015, International journal of clinical and experimental medicine.

[72]  Abeed Sarker,et al.  Pharmacovigilance from social media: mining adverse drug reaction mentions using sequence labeling with word embedding cluster features , 2015, J. Am. Medical Informatics Assoc..

[73]  J. Shepherd,et al.  The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation. , 2016, Health technology assessment.

[74]  G. Perkins,et al.  Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi - a systematic review and economic evaluation. , 2016, Health technology assessment.

[75]  F. Magro,et al.  A Systematic Review on Infliximab and Adalimumab Drug Monitoring: Levels, Clinical Outcomes and Assays , 2016, Inflammatory bowel diseases.

[76]  J. Kierkuś,et al.  Efficacy and Safety of Adalimumab for Paediatric Crohn's Disease: A Systematic Review. , 2016, Journal of Crohn's & colitis.

[77]  K. Getz,et al.  A Survey of Adverse Event Reporting Practices Among US Healthcare Professionals , 2016, Drug Safety.

[78]  Zheng-Yi Zhou,et al.  An indirect comparison and cost per responder analysis of adalimumab, methotrexate and apremilast in the treatment of methotrexate-naïve patients with psoriatic arthritis , 2016, Current medical research and opinion.

[79]  C. Carroll,et al.  Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model. , 2016, Health technology assessment.

[80]  C. Downey.  Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arthritis: A literature review , 2016, International journal of rheumatic diseases.

[81]  S. Paisley,et al.  Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review , 2016, Health technology assessment.

[82]  Xinlin Chen,et al.  Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis , 2016, BioDrugs.

[83]  G Savova,et al.  Capturing the Patient’s Perspective: a Review of Advances in Natural Language Processing of Health-Related Text , 2017, Yearbook of Medical Informatics.

[84]  Afonso Cavaco,et al.  The value of patient reporting to the pharmacovigilance system: a systematic review , 2017, British journal of clinical pharmacology.

[85]  J. Brownstein,et al.  Evaluation of Facebook and Twitter Monitoring to Detect Safety Signals for Medical Products: An Analysis of Recent FDA Safety Alerts , 2017, Drug Safety.

[86]  Abeed Sarker,et al.  Hybrid Semantic Analysis for Mapping Adverse Drug Reaction Mentions in Tweets to Medical Terminology , 2017, AMIA.

[87]  R. Merchant,et al.  Health‐related Google searches performed by parents of pediatric oncology patients , 2019, Pediatric blood & cancer.

[88]  Amy B Stein,et al.  Adverse Events Due to Insomnia Drugs Reported in a Regulatory Database and Online Patient Reviews: Comparative Study , 2019, Journal of medical Internet research.

[89]  Jianpin Liu,et al.  Comparison of drug safety data obtained from the monitoring system, literature, and social media: An empirical proof from a Chinese patent medicine , 2019, PloS one.