Scott Evans

Professor Evans research interests include the design, monitoring, analyses, and reporting of and education in clinical trials and diagnostic studies. As a thought leader in clinical research methodologies, Professor Evans emphasizes the importance of depth of understanding the research questions, with a focus on pragmatic and patient-centric benefit:risk assessment. Professor Evans works closely with his friend and colleague, Professor Toshi Hamasaki, leading a team of researchers and students to advance clinical trial and diagnostic study science.

The desirability of outcome ranking (DOOR) is a patient-centric paradigm for the design, data monitoring, analysis, interpretation, and reporting of clinical trials and other research studies based on benefit-risk evaluation. The DOOR uses outcomes to analyze patients rather than patients to analyze outcomes by comparing the experiences of trial participants in different treatment arms by the desirability of the overall patient outcome. The ALRG is using DOOR in the Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized with Pseudomonas aeruginosa (PHAGE) and Dalbavancin as an Option for Treatment of S. aureus bacteremia (DOTS) clinical trials, and in observational studies such CRACKLE I which compared Colistin vs. Ceftazidime-avibactam in the Treatment of Infections due to Carbapenem-Resistant Enterobacteriaceae. The FDA has implemented a DOOR Fellowship through ORISE. The recommended statistical analysis plan (SAP) for DOOR and a freely-available online application (app: https://methods.bsc.gwu.edu/) implementing the recommended analyses are developed. A study design tool is in development.

The Master Protocol for Evaluating Multiple Infection Diagnostics (MASTERMIND) was developed to evaluate multiple diagnostics simultaneously within a single study, providing efficiencies of specimen collection and characterization. MASTERMIND offers central trial organization, standardization of methods and definitions, and common reference standards.

MASTERMIND was utilized to evaluate simultaneously the performance of nucleic acid amplification tests for the detection of Neisseria gonorrhoeae and Chlamydia trachomatis in extragenital sites. The study resulted in FDA clearance of the first two diagnostic tests for extragenital testing for these pathogens.

Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME) and Average Weighted Accuracy (AWA) provides a systematic and pragmatic approach to evaluate and compare diagnostic alternatives to aid in clinical decision-making based on diagnostic yield i.e., the distribution of true positives, true negatives, false positives, and false negatives. The value of the yield depends on the relative importance of false positive vs. false negative errors as different errors carry different consequences. However, prevalence and relative importance vary geographically and temporally. BED-FRAME and AWA were applied to design the RADICAL study that evaluated the utility of a host response–based diagnostic test in categorizing acute respiratory tract illness into bacterial, viral, or neither etiology, and in the analyses of a study comparing rapid molecular diagnostics platforms for the detection of resistance to imipenem in Acinetobacter species. An online app for implementing BED-FRAME / AWA analyses will be freely available.

Sequential, Multiple-Assignment, Randomized Trials for Comparing Personalized Antibiotic Strategies (SMART COMPASS) is a trial design that compares strategies for antibiotic decision-making. The strategies allow for therapeutic adjustment if resistance or intolerability is observed acknowledging that patient management is a dynamic sequence of decisions e.g., empiric and definitive therapy, with therapeutic adjustments made over time. Adjustments are tailored to the unique circumstances encountered with individual patients as new information e.g., AST results, becomes available. This pragmatic design mirrors clinical antibiotic treatment decision-making and identifies the patient management strategy that optimizes outcomes.

Intention-to-diagnose (ITD) in diagnostic studies is the analog to intention-to-treat (ITT) in clinical trials. Application of ITD carries similar protections for diagnostic studies, i.e., valid statistical inference e.g., error control during hypothesis testing and correct coverage probabilities for confidence interval estimates of sensitivity or specificity, and well-defined populations from which to estimate parameters and to generalize results. In parallel to ITT analyses for clinical trials, ITD analyses provides the most realistic and unbiased answer to the most relevant question for diagnostic tests – that is, how do they perform in clinical practice, by fully capturing the range of consequences associated with test implementation in the intended-use setting, in lieu of a clinical outcome study. Dr. Evans has developed statistical strategies to analyze diagnostic studies in the presence of possible equivocal and missing results. A freely-available online analysis tool is in development.

The Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT) is a framework for assessing and comparing the desirability of the outcomes of antibiotic selection strategies in the presence of drug resistance. It is desirable to select an antibiotic from the narrowest spectrum for which the target infection is susceptible. This minimizes toxicity, cost, and the development of resistance due to selective pressure.

Interviews of Professor Evans and his work can be found here:

1. Internationally Recognized Leader in Clinical Trials, Biostatistics, and Infectious Disease Research Joins the George Washington University.  https://publichealth.gwu.edu/content/internationally-recognized-leader-clinical-trials-biostatistics-and-infectious-disease. 2018.
2. How can Novel Statistical Methods Tackle Antibiotic Resistance? Interview with Scott Evans. Cytel Blog. http://www.cytel.com/blog/novel-statistics-antibiotic-resistance-scott-evans. 2017.
3. Q&A with Scott Evans, CHANCE Executive Editor. American Statistical Association. http://www.amstat.org/ASA/Publications/Q-and-As/Scott-Evans.aspx.
4. Outsmarting Superbugs. Plymouth Magazine. https://www.plymouth.edu/magazine/alumni-green/outsmarting-superbugs/. 2016.
5. Superbugs: An Epidemic Begins. Harvard Magazine. http://harvardmagazine.com/2014/05/superbug. 2014.
6. Stats + Stories on NPR: Superbug Statistics. https://statsandstories.net/health1/superbug-statistics. 2019.
7. Stats + Stories on NPR: Sports Statistics. https://soundcloud.com/statsandstories/sports-stats-in-2019/s-Fidnl. 2019.
    

Sites of Note

JOURNALS

CHANCE
Statistical Communications in Infectious Diseases

BOOKS

Fundamental Concepts for New Clinical Trialists
Sample Size Determination in Clinical Trials with Multiple Endpoints
Group-Sequential Clinical Trials with Multiple Co-Objectives

1. Evans SR, Patel R, Hamasaki T, Howard-Anderson J, Kinamon T, King HA, Collyar D, Cross HR, Chambers HF, Fowler Jr VG, Bouhcer HW. The future ain’t what it used to be…out with the old…in with the better: Antibacterial Resistance Leadership Group (ARLG) innovations. Clin Infect Dis 2023; 77:321–30.
2. Evans SR. Zeng L, Dai W. The DSMB: The Toughest Job in Clinical Trials. Published January 24, 2023. NEJM Evid 2023; 2 (2). DOI: https://doi.org/10.1056/EVIDctw2200220.
3. Evans SR, Hamasaki T. Weighing Evidence: Robustness vs. Quantity. JNCI: Journal of the National Cancer Institute, 115(1), 1–3. https://doi.org/10.1093/jnci/djac186. 2023.
4. Chambers HF, Cross HR, Souli M, Evans SR, Patel R, Fowler VG. The Antibacterial Resistance Leadership Group: Scientific Advancements and Future Directions. Clin Infect Dis 2023;77(S4):S279–87.
5. Evans SR. Independent Oversight of Clinical Trials through Data and Safety Monitoring Boards. NEJM Evid 2022; 1 (1). DOI: 10.1056/EVIDctw2100005
6. Evans SR. Radical Thinking: Scientific Rigor and Pragmatism. Statistics in Biopharmaceutical Research, 14:2, 140-152, 2022. https://doi.org/10.1080/19466315.2022.2026460.
7. Evans SR. Our Most Important Discovery: The Question. Statistics in Biopharmaceutical Research, 14:4, 398-407, 2022. https://doi.org/10.1080/19466315.2021.1972833.
8. Evans SR. Paraoan D, Perlmutter J, Raman SR, Sheehan JJ, Hallinan ZP. Real‑World Data for Planning Eligibility Criteria and Enhancing Recruitment: Recommendations from the Clinical Trials Transformation Initiative. Therapeutic Innovation & Regulatory Science. https://doi.org/10.1007/s43441-020-00248-7. 2021. May;55(3):545-552.
9. Evans SR. Waking up to p: Comment on “The Role of p-Values in Judging the Strength of Evidence and Realistic Replication Expectations”, Statistics in Biopharmaceutical Research, 13:1, 19-21, DOI: 10.1080/19466315.2020.1811151. 2021.
10. Benjamini Y, De Veaux RD, Efron B, Evans S, Glickman M, Graubard BI, He X, Meng XL, Reid NM, Stigler SM, Vardeman SB, Wikle CK, Wright T, Young LJ, Kafadar K. ASA President’s Task Force Statement on Statistical Significance and Replicability. The Annals of Applied Statistics. Vol. 15, No. 3, 1084–1085. https://doi.org/10.1214/21-AOAS1501. © Institute of Mathematical Statistics, 2021.
11. Hamasaki T, Hung HMJ, Hsiao, CF, Evans SR. On selecting the critical boundary functions in group-sequential trials with two time-to-event outcomes. Contemporary Clinical Trials. https://doi.org/10.1016/j.cct.2020.106244. 2021.
12. Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y. Ticagrelor and Aspirin versus Aspirin in Acute Ischemic Stroke or TIA. N Engl J Medicine. 2020.
13. Evans SR, Knutsson M, Amarenco P, Albers GW, Bath PN, Denison H, Ladenvall P, Jonasson J, Easton JD, Minematsu K, Molina CA, Wang Y, Wong KSL, Johnston SC. Methodologies for pragmatic and efficient assessment of benefits and harms: application to the SOCRATES trial. Clinical Trials, Vol. 17(6) 617–626, 2020.
14. Evans SR, Bigelow R, Chuang-Stein C, Ellenberg S, Gallo P, He W, Jiang Q, Rockhold F. Presenting Risks and Benefits: Helping the Data Monitoring Committee Do Its Job. Annals of Internal Medicine. 2020.
15. Liu Y, Tsalik EL, Jiang Y, Ko ER, Woods CW, Henao R, Evans SR. Average Weighted Accuracy (AWA): Pragmatic Analysis for a RADICAL Study. Clin Infect Dis.; 2020.
16. Evans SR, DeGruttola V. Innovations in Design, Education, and Analysis (IDEA) Introduction. Clin Infect Dis.; 2019;68(11):1960.
17. Jiang Y, Follmann D, Evans SR. Superbug Clinical Trials. Wiley StatsRef-Statistics Reference Online. 2019.
18. Evans SR, Follmann D, Liu Y, Holland T, Doernberg SB, Rouphael N, Hamasaki T, Jiang Y, Lok JL, Tran TTT, Harris AD, Fowler, Jr. VG, Boucher H, Kreiswirth BN, Bonomo RA, van Duin D, Paterson DL, Chambers H. Sequential Multiple Assignment Randomized Trials for COMparing Personalized Antibiotic StrategieS (SMART-COMPASS). Clin Infect Dis. 2019;68(11):1961–7. PMID: 30351426 PMC Journal - In Process
19. Evans SR, Tran TTT, Hujer AM, Hill CB, Hujer KM, Mediavilla JR, Manca C, Domitrovic TN, Perez F, Farmer M, Pitzer KM, Wilson BM, Kreiswirth BN, Patel R, Jacobs MR, Chen L, Fowler Jr VG, Chambers HF, Bonomo RA; Antibacterial Resistance Leadership Group (ARLG). Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against Pseudomonas aeruginosa: PRIMERS IV. Clin Infect Dis. 2019;68(11):1961–7. PMID: 30351426 PMC Journal - In Process
20. Evans, SR, Rubin DB, Powers JH, Follmann D. Analysis Populations in Anti-infective Clinical Trials: Whom to Analyze? Stat Commun Infect Dis. 2018; NIHMSID 988165
21. Hamasaki T, Evans SR, Asakura K. Design, data monitoring, and analysis of clinical trials with co-primary endpoints: a review. J Biopharm Stat. 2018; 28(1):28-51. PMID: 29083951 PMCID: PMC6135538
22. Huskins WC, Fowler Jr VG, Evans SR. Adaptive Designs for Clinical Trials:  Application to Healthcare Epidemiology Research. Clin Infect Dis. 2018; 66(7):1140-46. PMID: 29121202 PMCID: PMC6018921
23. Van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler Jr VG, Paterson DL, Bonomo RA, Evans SR. Colistin vs. Ceftazidime-avibactam in the Treatment of Infections due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018; 66(2):163-171. PMID: 29020404 PMCID: PMC5850032
24. Evans SR, Powers J. Evaluating Anti-Infective Drugs in the Resistant Pathogen Setting: Can we Use External Controls? Stat Commun Infect Dis. 2017; 9(1): 20160003. PMID: 28757914 PMCID: PMC5529043 
25. Patel R, Tsalik EL, Petzold E, Fowler Jr. VG, Klausner JD, Evans SR. Antibacterial Resistance Leadership Group (ARLG). MASTERMIND: Bringing Microbial Diagnostics to the Clinic. Clin Infect Dis. 2017; 64(3):355-360. PMID: 27927867 PMCID: PMC5894935
26. Huvane J, Komarow L, Hill C, Tran TT, Pereira C, Rosenkranz S, Finnemeyer M, Earley M, Jiang HJ, Wang R, Lok J, Evans SR; Statistical and Data Management Center of the Antibacterial Resistance Leadership Group (ARLG). Fundamentals and Catalytic Innovation: The Statistical and Data Management Center of the Antibacterial Resistance Leadership Group. Clin Infect Dis. 2017; 64(suppl_1):S18-S23. PMID: 28350899 PMCID: PMC5848245
27. Evans SR, Harris AD. Methods and issues in studies of CRE. Virulence. 2017; 8(4):453-459. PMID: 27470534 PMCID: PMC5477696
28. Asakura K, Hamasaki T, Evans SR. Interim evaluation of efficacy or futility in group-sequential trials with multiple co-primary endpoints. Biom J. 2017; 59(4):703-731. PMID: 27757980 PMCID: PMC6222168
29. Evans SR, Hujer AM, Jiang H, Hill CB, Hujer KM, Mediavilla JR, Manca C, Tran TT, Domitrovic TN, Higgins PG, Seifert H, Kreiswirth BN, Patel R, Jacobs MR, Chen L, Sampath R, Hall T, Marzan C, Fowler Jr VG, Chambers HF, Bonomo RA. Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics to Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III. J Clin Microbiol. 2016; 55(1):134-144. PMID: 27795336 PMCID: PMC5228224
30. Evans SR, Follmann D. Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A Step toward Pragmatism in Benefit:risk Evaluation. Stat Biopharm Res. 2016; 8(4):386-393. PMID: 28435515 PMCID: PMC5394932
31. Evans SR, Pennello G, Pantoja-Galicia N, Jiang H, Hujer AM, Hujer KM, Manca C, Hill C, Jacobs MR, Chen L, Patel R, Kreiswirth BN, Bonomo RA. Benefit-risk Evaluation for Diagnostics: A Framework (BED-FRAME). Clin Infect Dis. 2016; 63(6):812-7. PMID: 27193750 PMCID: PMC4996133
32. Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong L; SOCRATES Steering Committee and Investigators. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Medicine. 2016; 375(1):35-43. PMID: 27160892
33. Pennello G, Pantoja-Galicia N, Evans SR. Comparing diagnostic tests on benefit-risk. J Biopharm Stat. 2016; 26(6):1083-1097. PMID: 27548805 PMCID: PMC5471848
34. Evans SR, Hujer AM, Jiang H, Hujer KM, Hall T, Marzan C, Jacobs MR, Sampath R, Ecker DJ, Manca C, Chavda K, Zhang P, Fernandez H, Chen L, Mediavilla JR, Hill CB, Perez F, Caliendo AM, Fowler Jr. VG, Chambers HF, Kreiswirth BN, and Bonomo RA;  Antibacterial Resistance Leadership Group. Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II. Clin Infect Dis. 2016; 62(2):181-9. PMID: 26409063 PMCID: PMC4690483
35. Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D,  Chuang-Stein C, Cosgrove SE, Fowler Jr. VG, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015; 61(5):800-6. PMID: 26113652 PMCID: PMC4542892
36. Uno H, Wittes J, Fu H, Solomon SD, Claggett B, Tian L, Cai T, Pfeffer MA, Evans SR, Wei LJ. Alternatives to hazard ratios for comparing efficacy or safety of therapies in noninferiority studies. Ann Intern Med. 2015; 163:127-134. PMID: 26054047 PMCID: PMC4510023.
37. Evans SR, Ellis RJ, Chen H, Yeh TM, Lee AJ, Schifitto G, Wu K, Bosch RJ, McArthur JC, Simpson DM, Clifford DB. Peripheral Neuropathy in HIV: Prevalence and Risk Factors. AIDS. 2011; 25(7):919-28. PMID: 21330902 PMCID: PMC3196556
38. Evans SR. Fundamentals of Clinical Trial Design. J Exp Stroke Transl Med. 2010; 3(1):19-27. PMID: 21533012 PMCID: PMC3083073
39. Evans SR. Clinical Trial Structures. J Exp Stroke Transl Med. 2010; 3(1):8-18. PMID: 21423788 PMCID: PMC3059315
40. Evans SR. Common Statistical Concerns in Clinical Trials. J Exp Stroke Transl Med. 2010; 3(1):1-7. PMID: 21423790 PMCID: PMC3059317
41. Evans SR. Estudos Clinicos de Nao-Inferioridade. Revista Brasileira de Medicina. 2010; 3(1):1-7.
42. Evans SR, Li L, Wei LJ. Data Monitoring in Clinical Trials Using Prediction. Drug Inf J. 2007; 41(6):733-742.
43. Evans SR, Fichtenbaum CJ, Aberg JA; A5087 Study Team. Comparison of Direct and Indirect Measurement of LDL-C in HIV Infected Individuals: ACTG 5087. HIV Clin Trials. 2007; 8(1):45-52. PMID: 17434848 PMCID: PMC2288650
44. Evans SR. When and How Can Endpoints Be Changed After Initiation of a Randomized Clinical Trial? PLoS Clin Trials. 2007; 2(4):e18. PMID: 17443237 PMCID: PMC1852589
45. Evans SR, Simpson DM, Kitch DW, King A, Clifford DB, Cohen BA, McArthur JC; Neurologic AIDS Research Consortium; AIDS Clinical Trials Group. A Randomized Trial Evaluating Prosaptide™ for HIV-Associated Sensory Neuropathies: Use of an Electronic Diary to Record Neuropathic Pain. PLoS One. 2007; 2(6):e551. PMID: 17653259 PMCID: PMC1919427
46. Evans SR, Wang R, Yeh TM, J Anderson, Haija R, McBratney-Owen PM, Peeples L,  Sinha S, Xanthakis V, Rajicic N, Zhang J. Evaluation of Distance Learning in an Introduction to Biostatistics Course. Statistical Education Research Journal. 2007; 6(2):59-77.
47. Evans SR, Li L. A Comparison of Goodness of Fit Tests for the Logistic GEE Model. Stat Med. 2005; 24(8):1245-61. PMID: 15580592
48. Evans SR, Hosmer DW. Goodness of Fit Tests for Mixed Effects Logistic Models Characterized by Clustering. Commun Stat Theory Methods. 2004; 33(5):1139-1155.
49. Evans SR, Hosmer DW. Goodness of Fit Tests for Logistic GEE Models: Simulation Results. Commun Stat Simul Comput. 2004; 33(1):247-258.
50. Evans SR, Krown SE, Testa MA, Cooley TP, Von Roenn JH. A Phase II Evaluation of Low-Dose Oral Etoposide for the Treatment of Relapsed or Progressive AIDS-Related Kaposi's Sarcoma: An ACTG Clinical Study. J Clin Oncol. 2002; 20(15):3236-41. PMID: 12149296 

• PUBH 6866: Principles of Clinical Trials
• PUBH 6899: Advanced Topics in Clinical Trials

Dr. Evans has delivered keynote addresses at many conferences such as the Regulatory Industry Statistics Workshop, FDA / AdvaMed Medical Device Statistical Issues Conference, the Applied Statistics Symposium of the International Chinese Statistical Association, the Deming Conference on Applied Statistics, the Graybill Conference, the Japanese Biometric Society, Interfarma and ANVISAs’ Multidisciplinary Symposium on Noninferiority Trials in Brazil,  the University of Maryland Baltimore County (UMBC) Probability and Statistics Day, and the Statistics in Pharmaceuticals (SIP) conference.

Professor Evans has served on more than 100 DSMBs for government and industry-sponsored clinical trials.

Dr. Evans serves on an FDA Advisory Committee.

Professor Evans was the Editor of a Statistical Mini-Series "Independent Oversight of Clinical Trials: Protecting Patients and Scientific Integrity" for the New England Journal of Medicine (NEJM) Evidence.  He is the former Editor-in-Chief of CHANCE, the former Co-Editor of a Special Section of Clinical Infectious Diseases (CID) entitled Innovations in Design, Education, and Analysis (IDEA), and Advisory Editor for Statistics in Biopharmaceutical Research, and the Editor-in-Chief of Statistical Communications in Infectious Diseases (SCID).

Professor Evans is the Past-President of the Boston Chapter of the ASA, the Past-Chair of the Development Committee of ASA, the Past-Chair of the Teaching Statistics in the Health Sciences section of ASA, the Past-Chair of the Medical Devices and Diagnostics section of the ASA, and the Past-Chair of the Statistics in Sports section of ASA. He is the Co-founder of the biennial New England Symposium on Statistics in Sports (NESSIS).

Professor Evans is a former member of the Board of Directors for the American Statistical Association (ASA), the Society for Clinical Trials (SCT), and the Mu Sigma Rho (the National Honorary Society for Statistics). He has been a member of the Steering Committee of the Clinical Trials Transformation Initiative (CTTI), the Executive Committee for the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, and Networks (ACTTION), and served as the Chair of the Trial of the Year Committee of the SCT.