Improving the analysis of adverse event data in randomized controlled trials

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592 · see citing works

Developing core outcome sets for clinical trials: issues to consider

Williamson, P. R., Altman, D. G., Blazeby, J. M., Clarke, M., Devane, D., Gargon, E., & Tugwell, P. (2012) · Trials · doi:10.1186/1745-6215-13-132 · Cited by 1,661 · see citing works

Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement

Ioannidis, J. P. A., Evans, S. J. W., Gøtzsche, P. C., O'Neill, R. T., Altman, D. G., Schulz, K., Moher, D., & for the CONSORT Group* (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-141-10-200411160-00009 · Cited by 1,593 · see citing works

Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease

Kröger, N. M., Solano, C., Wolschke, C., Bandini, G., Patriarca, F. F., Pini, M., Nagler, A., Selleri, C., Risitano, A. M., Messina, G., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1506002 · Cited by 574 · see citing works

Harmonisation in Pharmacovigilance

Edwards, I. R., & Biriell, C. (1994) · Drug Safety · doi:10.2165/00002018-199410020-00001 · Cited by 396 · see citing works

Consequences of dichotomization

Fedorov, V., Mannino, F., & Zhang, R. (2009) · Pharmaceutical Statistics · doi:10.1002/pst.331 · Cited by 303 · see citing works

Reporting of Safety Results in Published Reports of Randomized Controlled Trials

(2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2009.306 · Cited by 287 · see citing works

Drug safety assessment in clinical trials: methodological challenges and opportunities

Singh, S., & Loke, Y. K. (2012) · Trials · doi:10.1186/1745-6215-13-138 · Cited by 228 · see citing works

Analysis and reporting of adverse events in randomised controlled trials: a review

Phillips, R., Hazell, L., Sauzet, O., & Cornelius, V. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-024537 · Cited by 228 · see citing works

Brief Communication: Better Ways To Question Patients about Adverse Medical Events: A Randomized, Controlled Trial

Bent, S., Padula, A., & Avins, A. L. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-144-4-200602210-00007 · Cited by 177 · see citing works

Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial

Lincoff, A. M., Mehran, R., Povsic, T. J., Zelenkofske, S. L., Huang, Z., Armstrong, P. W., Steg, P. G., Bode, C., Cohen, M. G., Buller, C. E. H., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00515-2 · Cited by 161 · see citing works

Adherence to therapy and adverse drug reactions: is there a link?

Leporini, C., Sarro, G. D., & Russo, E. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2014.947260 · Cited by 150 · see citing works

Inadequate statistical power to detect clinically significant differences in adverse event rates in randomized controlled trials

Tsang, R., Colley, L., & Lynd, L. D. (2008) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2008.08.005 · Cited by 139 · see citing works

Recommendations for safety planning, data collection, evaluation and reporting during drug, biologic and vaccine development: a report of the safety planning, evaluation, and reporting team

Crowe, B. J., Xia, H. A., Berlin, J. A., Watson, D. J., Shi, H., Lin, S. L., Kuebler, J., Schriver, R. C., Santanello, N. C., Rochester, G., et al. (2009) · Clinical Trials · doi:10.1177/1740774509344101 · Cited by 118 · see citing works

Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective

Lineberry, N. B., Berlin, J. A., Mansi, B. A., Glasser, S. C., Berkwits, M., Klem, C., Bhattacharya, A., Citrome, L., Enck, R. E., Fletcher, J., et al. (2016) · BMJ · doi:10.1136/bmj.i5078 · Cited by 115 · see citing works

Gold Standards in Pharmacovigilance

Hauben, M., & Aronson, J. K. (2007) · Drug Safety · doi:10.2165/00002018-200730080-00001 · Cited by 86 · see citing works

Embracing model-based designs for dose-finding trials

Love, S., Brown, S., Weir, C. J., Harbron, C. G., Yap, C., Gaschler‐Markefski, B., Matcham, J., Caffrey, L., McKevitt, C., Clive, S., et al. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.186 · Cited by 65 · see citing works

On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies

Unkel, S., Amiri, M., Benda, N., Beyersmann, J., Knoerzer, D., Kupas, K., Langer, F., Leverkus, F., Loos, A. H., Ose, C., et al. (2018) · Pharmaceutical Statistics · doi:10.1002/pst.1915 · Cited by 65 · see citing works

Time to improve the reporting of harms in randomized controlled trials

Junqueira, D. R., Phillips, R., Zorzela, L., Golder, S., Loke, Y. K., Moher, D., Ioannidis, J. P. A., & Vohra, S. (2021) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2021.04.020 · Cited by 65 · see citing works

Bayesian Hierarchical Modeling for Detecting Safety Signals in Clinical Trials

Xia, H. A., Ma, H., & Carlin, B. P. (2011) · Journal of Biopharmaceutical Statistics · doi:10.1080/10543406.2010.520181 · Cited by 64 · see citing works

Adverse event reporting in randomised controlled trials of neuropathic pain: Considerations for future practice

Cornelius, V. R., Sauzet, O., Williams, J. E., Ayis, S., Farquhar-Smith, P., Ross, J. R., Branford, R. A., & Peacock, J. L. (2013) · Pain · doi:10.1016/j.pain.2012.08.012 · Cited by 49 · see citing works

Secondary use of randomized controlled trials to evaluate drug safety: a review of methodological considerations

Hammad, T. A., Pinheiro, S. P., & Neyarapally, G. A. (2011) · Clinical Trials · doi:10.1177/1740774511419165 · Cited by 47 · see citing works

Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for non-systematic adverse events

Mayo‐Wilson, E., Fusco, N., Hong, H., Li, T., Canner, J. K., & Dickersin, K. (2019) · Trials · doi:10.1186/s13063-019-3581-3 · Cited by 37 · see citing works

Statistical methods for the analysis of adverse event data in randomised controlled trials: a scoping review and taxonomy

Phillips, R., Sauzet, O., & Cornelius, V. R. (2020) · BMC Medical Research Methodology · doi:10.1186/s12874-020-01167-9 · Cited by 36 · see citing works

Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials

Dimairo, M., Julious, S. A., Todd, S., Nicholl, J. P., & Boote, J. D. (2015) · Trials · doi:10.1186/s13063-015-1119-x · Cited by 32 · see citing works

Survival analysis for AdVerse events with VarYing follow‐up times (SAVVY): Rationale and statistical concept of a meta‐analytic study

Stegherr, R., Beyersmann, J., Jehl, V., Rufibach, K., Leverkus, F., Schmoor, C., & Friede, T. (2020) · Biometrical Journal · doi:10.1002/bimj.201900347 · Cited by 24 · see citing works

Advantages of visualisations to evaluate and communicate adverse event information in randomised controlled trials

Cornelius, V. R., Cro, S., & Phillips, R. (2020) · Trials · doi:10.1186/s13063-020-04903-0 · Cited by 24 · see citing works

Understanding current practice, identifying barriers and exploring priorities for adverse event analysis in randomised controlled trials: an online, cross-sectional survey of statisticians from academia and industry

Phillips, R., & Cornelius, V. R. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-036875 · Cited by 23 · see citing works

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

Patson, N., Mukaka, M., Otwombe, K. N., Kazembe, L. N., Mathanga, D. P., Mwapasa, V., Kabaghe, A. N., Eijkemans, M. J. C., Laufer, M. K., & Chirwa, T. F. (2020) · Malaria Journal · doi:10.1186/s12936-020-03190-z · Cited by 22 · see citing works

Statistical Monitoring of Safety in Clinical Trials

Zhu, L., Yao, B., Xia, H. A., & Jiang, Q. (2015) · Statistics in Biopharmaceutical Research · doi:10.1080/19466315.2015.1117017 · Cited by 20 · see citing works

The reporting of harms in publications on randomized controlled trials funded by the “Programme Hospitalier de Recherche Clinique,” a French academic funding scheme

Favier, R., & Crépin, S. (2018) · Clinical Trials · doi:10.1177/1740774518760565 · Cited by 19 · see citing works

A Framework for Safety Evaluation Throughout the Product Development Life-Cycle

Ball, G., Reblin, T., Buchanan, J. R., Hendrickson, B. A., Lewis, E., Schnell, P., & Rockhold, F. W. (2019) · Therapeutic Innovation & Regulatory Science · doi:10.1007/s43441-019-00021-5 · Cited by 17 · see citing works

Statistical Practices of Safety Monitoring: An Industry Survey

Colopy, M. W., Gordon, R. M., Ahmad, F., Wang, W. W., Duke, S. P., & Ball, G. (2018) · Therapeutic Innovation & Regulatory Science · doi:10.1177/2168479018779973 · Cited by 6 · see citing works

Improving analysis practice of continuous adverse event outcomes in randomised controlled trials - a distributional approach

Ster, A. C., Phillips, R., Sauzet, O., & Cornelius, V. R. (2021) · Trials · doi:10.1186/s13063-021-05343-0 · Cited by 5 · see citing works

Interdisciplinary Safety Evaluation and Quantitative Safety Monitoring: Introduction to a Series of Papers

Seltzer, J. H., Li, J., & Wang, W. Y. (2019) · Therapeutic Innovation & Regulatory Science · doi:10.1177/2168479018793130 · Cited by 4 · see citing works

SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials

Hróbjartsson, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · BMJ · doi:10.1136/bmj-2024-081660 · Cited by 171 · see citing works

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms

Yepes-Núñez, J. J., Guyatt, G. H., Gómez-Escobar, L. G., Pérez-Herrera, L. C., Chu, A. W. L., Ceccacci, R., Acosta, A. S., Wen, A., Moreno, S., MacDonald, M., et al. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.09.020 · Cited by 100 · see citing works

Topical corticosteroids for hives and itch (urticaria): Systematic review and Bayesian meta-analysis of randomized trials

Chu, A. W. L., Rayner, D. G., Chu, X., Chen, L., Dong, A., Waserman, S., Baker, D. R., Sheikh, J. K., Moellman, J. J., Lang, D. M., et al. (2024) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2024.06.003 · Cited by 15 · see citing works

First, do no harm: a call to action to improve the evaluation of harms in clinical exercise research

Thomsen, S. N., Lucía, A., Spence, R. R., Benatti, F. B., Joyner, M. J., Berg, R. M. G., Ried‐Larsen, M., & Simonsen, C. (2024) · British Journal of Sports Medicine · doi:10.1136/bjsports-2023-107579 · Cited by 9 · see citing works

Comparing the Value of Data Visualization Methods for Communicating Harms in Clinical Trials

Qureshı, R., Chen, X., Goerg, C., Mayo‐Wilson, E., Dickinson, S., Golzarri‐Arroyo, L., Hong, H., Phillips, R., Cornelius, V. R., McAdams‐DeMarco, M., et al. (2022) · Epidemiologic Reviews · doi:10.1093/epirev/mxac005 · Cited by 8 · see citing works

Inclusion of harm outcomes in core outcome sets requires careful consideration

Tay, J., Robinson, C., Blazeby, J. M., Loke, Y. K., Lowery, A., Alkhaffaf, B. H., & Kirkham, J. J. (2024) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2024.111474 · Cited by 8 · see citing works

The Safety of Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer: An Individual-Participant Data Meta-Analysis Based on 14 Randomized Clinical Trials

Shaver, A. L., Nikita, N., Sharma, S., Keith, S. W., Zarrabi, K. K., Kelly, W. K., & Lu-Yao, G. L. (2025) · Cancers · doi:10.3390/cancers17172747 · Cited by 7 · see citing works

Antidepressants for low back pain and spine-related leg pain

Ferraro, M. C., Urquhart, D. M., Ferreira, G. E., Wewege, M. A., Shaheed, C. A., Traeger, A. C., Hoving, J. L., Visser, E., McAuley, J. H., & Cashin, A. G. (2025) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001703.pub4 · Cited by 7 · see citing works

Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century

Janani, L., Phillips, R., Vogt, E. V., Liu, X., Waddington, C. S., & Cro, S. (2024) · Clinical & Experimental Immunology · doi:10.1093/cei/uxae104 · Cited by 8 · see citing works

Inadequate Reporting of Harm From Randomized Clinical Trials in Top Medical Publications

Zheng, R., Tao, L., Sun, Y., Shang, H., & Levine, M. (2025) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.70006 · Cited by 6 · see citing works

Statistical methods leveraging the hierarchical structure of adverse events for signal detection in clinical trials: a scoping review of the methodological literature

Nunes, L. D. A., Hooper, R., McGettigan, P., & Phillips, R. (2024) · BMC Medical Research Methodology · doi:10.1186/s12874-024-02369-1 · Cited by 4 · see citing works

Future directions of research into harms in randomised controlled trials

Phillips, R., & Cornelius, V. R. (2023) · BMJ · doi:10.1136/bmj.p926 · Cited by 3 · see citing works

Evaluating Adverse Event Reporting in Parallel-Group Randomized Trials Published in Dermatology-Specific Journals: A Methodological Systematic Review

Song, Z., Pymento, J., Bortoluzzi, T., Vyas, M. V., Uleryk, E. M., & Chan, A. (2025) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.02.144 · Cited by 2 · see citing works

How Can We Quantify and Compare Harm in Surgical Trials?

Protasio, J. N., King, A. J., Pasquale, L. R., Barton, K., Bonnar, J., Qureshı, R., Virgili, G., & Azuara‐Blanco, A. (2022) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2022.04.020 · Cited by 2 · see citing works

Clinical utility of overviews on adverse events of pharmacological interventions

Sachse, T., Kanji, S., Thabet, P., Schmiedl, S., Thürmann, P., Guirguis, F., Sajwani, S., Gauthier, M.-F., Lunny, C., Mathes, T., et al. (2023) · Systematic Reviews · doi:10.1186/s13643-023-02289-z · Cited by 2 · see citing works

Protocol for a novel approach to developing a single pan-specialty ‘meta-core outcome set’: An example from the field of surgical oncology

Tay, J., Blazeby, J. M., O’Neill, A., Loke, Y. K., Lowery, A., Robinson, C., Alkhaffaf, B. H., & Kirkham, J. J. (2025) · HRB Open Research · doi:10.12688/hrbopenres.14058.1 · Cited by 1 · see citing works

A multicenter trial-based economic evaluation of a mobile health intervention for individuals with chronic non-specific low back pain: randomized controlled trial protocol

Mota, M. A. D. A., Landolfi, T. B., Silva, M. C. D. M., Santana, B. D. M., Ben, Â. J., van Dongen, J. M., Bosmans, J. E., Ostelo, R., Burke, T. N., Pasinato, F., et al. (2025) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-025-09118-5 · Cited by 1 · see citing works

Potassium-competitive acid blockers versus proton pump inhibitors: redefining the standards of care in reflux esophagitis

Scarpignato, C., & Gatta, L. (2025) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000003052 · Cited by 1 · see citing works

Harm outcomes applicable for most meta-analyses of randomized trials of biomedical interventions: a key concept in clinical epidemiology

Christensen, R., Berthelsen, D. B., Tugwell, P., Golder, S., Qureshi, R., Mayo‐Wilson, E., Simon, L. S., Kwong, J. S., Williamson, P. R., & Vohra, S. (2026) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2026.112218 · Cited by 1 · see citing works

A proposal for using benefit-risk methods to improve the prominence of adverse event results when reporting trials

Totton, N., Waddingham, E., Owen, R., Julious, S. A., Hughes, D. A., & Cook, J. A. (2024) · Trials · doi:10.1186/s13063-024-08228-0 · Cited by 1 · see citing works

Trials special series - the collection, analysis and reporting of adverse events in randomised controlled trials

Phillips, R., & Cornelius, V. R. (2025) · Trials · doi:10.1186/s13063-025-08861-3 · Cited by 1 · see citing works

Good Data Science Practice: Moving toward a Code of Practice for Drug Development (Rejoinder)

Baillie, M., Moloney, C., Mueller, C. P., Dorn, J. F., Branson, J., & Ohlssen, D. I. (2023) · Statistics in Biopharmaceutical Research · doi:10.1080/19466315.2022.2128402

Additional file 2 of Clinical utility of overviews on adverse events of pharmacological interventions

Sachse, T., Kanji, S., Thabet, P., Schmiedl, S., Thürmann, P., Guirguis, F., Sajwani, S., Gauthier, M.-F., Lunny, C., Mathes, T., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607562

Additional file 5 of Clinical utility of overviews on adverse events of pharmacological interventions

Sachse, T., Kanji, S., Thabet, P., Schmiedl, S., Thürmann, P., Guirguis, F., Sajwani, S., Gauthier, M.-F., Lunny, C., Mathes, T., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607571

Additional file 4 of Clinical utility of overviews on adverse events of pharmacological interventions

Sachse, T., Kanji, S., Thabet, P., Schmiedl, S., Thürmann, P., Guirguis, F., Sajwani, S., Gauthier, M.-F., Lunny, C., Mathes, T., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607568

Additional file 1 of Clinical utility of overviews on adverse events of pharmacological interventions

Sachse, T., Kanji, S., Thabet, P., Schmiedl, S., Thürmann, P., Guirguis, F., Sajwani, S., Gauthier, M.-F., Lunny, C., Mathes, T., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607559

Additional file 3 of Clinical utility of overviews on adverse events of pharmacological interventions

Sachse, T., Kanji, S., Thabet, P., Schmiedl, S., Thürmann, P., Guirguis, F., Sajwani, S., Gauthier, M.-F., Lunny, C., Mathes, T., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26607565

Reporting of the harms from randomized controlled trials for psoriasis: a cross-sectional meta-epidemiological study

Yang, Z., Xiong, Y., Shen, Y., Cheng, Z., Dai, Y., Hao, P., & Hu, Z. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1734221

A four-year retrospective surgical case series examining postoperative complications following Removal of Silicone Oil (ROSO) scored using the Complications of Retinal Detachment Surgery (CORDS) severity classification tool

Scantling‐Birch, Y., Relwani, S., Mckechnie, C. J., & Zambarakji, H. (2026) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-026-07463-2

Analysis and reporting of adverse events in randomised controlled trials: a review

Phillips, R., Hazell, L., Sauzet, O., & Cornelius, V. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-024537 · Cited by 228 · see citing works

Statistical methods for the analysis of adverse event data in randomised controlled trials: a scoping review and taxonomy

Phillips, R., Sauzet, O., & Cornelius, V. R. (2020) · BMC Medical Research Methodology · doi:10.1186/s12874-020-01167-9 · Cited by 36 · see citing works

Understanding current practice, identifying barriers and exploring priorities for adverse event analysis in randomised controlled trials: an online, cross-sectional survey of statisticians from academia and industry

Phillips, R., & Cornelius, V. R. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-036875 · Cited by 23 · see citing works

Examining current practice for the analysis and reporting of harm outcomes in phase II and III pharmacology trials: exploring methods to facilitate improved detection of adverse drug reactions

Phillips, R. (2021) · doi:10.25560/100776

Assessment of Harm

Papanikolaou, P. N. (2012) · Chapman & Hall/CRC eBooks · doi:10.1201/b11349-9