Guidance on interim analysis methods in clinical trials

Power failure: why small sample size undermines the reliability of neuroscience

Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò, M. R. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3475 · Cited by 7,641 · cited 1× · see citing works

A Multiple Testing Procedure for Clinical Trials

O'Brien, P. C., & Fleming, T. R. (1979) · Biometrics · doi:10.2307/2530245 · Cited by 3,311 · see citing works

Discrete sequential boundaries for clinical trials

GORDON LAN, K. K., & DEMETS, D. L. (1983) · Biometrika · doi:10.1093/biomet/70.3.659 · Cited by 2,310 · see citing works

Fundamentals of Clinical Trials

Friedman, L. M., Furberg, C. D., DeMets, D. L., Reboussin, D. M., & Granger, C. B. (2015) · doi:10.1007/978-3-319-18539-2 · Cited by 2,237 · see citing works

Group sequential methods in the design and analysis of clinical trials

POCOCK, S. J. (1977) · Biometrika · doi:10.1093/biomet/64.2.191 · Cited by 1,831 · see citing works

Group Sequential Methods with Applications to Clinical Trials

Jennison, C., & Turnbull, B. W. (1999) · Chapman & Hall/CRC eBooks · doi:10.1201/9780367805326 · Cited by 1,361 · see citing works

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

Campbell, B. C. V., Mitchell, P. J., Churilov, L. P., Yassi, N., Kleinig, T. J., Dowling, R., Yan, B., Bush, S. J., Dewey, H. M., Thijs, V., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716405 · Cited by 899 · see citing works

Randomized versus historical controls for clinical trials

Sacks, H., Chalmers, T. C., & Smith, H. (1982) · The American Journal of Medicine · doi:10.1016/0002-9343(82)90815-4 · Cited by 834 · see citing works

Interim analysis: The alpha spending function approach

DeMets, D. L., & Lan, K. K. G. (1994) · Statistics in Medicine · doi:10.1002/sim.4780131308 · Cited by 565 · see citing works

Designed Extension of Studies Based on Conditional Power

Proschan, M. A., & Hunsberger, S. (1995) · Biometrics · doi:10.2307/2533262 · Cited by 536 · see citing works

The role of internal pilot studies in increasing the efficiency of clinical trials

Wittes, J. T., & Brittain, E. (1990) · Statistics in Medicine · doi:10.1002/sim.4780090113 · Cited by 440 · see citing works

Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke

Johnston, K. C., Bruno, A., Pauls, Q., Hall, C. E., Barrett, K. M., Barsan, W. G., Fansler, A. C., van de Bruinhorst, K., Janis, S., Durkalski‐Mauldin, V. L., et al. (2019) · JAMA · doi:10.1001/jama.2019.9346 · Cited by 416 · see citing works

Interim Analyses for Randomized Clinical Trials: The Group Sequential Approach

Pocock, S. (1982) · Biometrics · doi:10.2307/2530298 · Cited by 265 · see citing works

Thrombectomy for Stroke in the Public Health Care System of Brazil

Martins, S. C. O., Montalverne, F. J., Rebello, L. C., Abud, D. G., Silva, G. S., Lima, F. O., Parente, B. S. M., Nakiri, G. S., Faria, M. B., Frudit, M. E., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2000120 · Cited by 233 · see citing works

Goodness-of-fit statistics for age-specific reference intervals

Royston, P. J., & Wright, E. M. (2000) · Statistics in Medicine · doi:10.1002/1097-0258(20001115)19:21 · Cited by 208 · see citing works

Statistical Monitoring of Clinical Trials: a Unified Approach

Chernick, M. R. (2007) · Technometrics · doi:10.1198/tech.2007.s479 · Cited by 190 · see citing works

Sample size re‐estimation in clinical trials

Proschan, M. A. (2009) · Biometrical Journal · doi:10.1002/bimj.200800266 · Cited by 132 · see citing works

Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease

Sperling, R. A., Henley, D. B., Aisen, P. S. S., Raman, R., Donohue, M., Ernstrom, K. B., Rafii, M. S., Streffer, J. R., Shi, Y., Karcher, K., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4857 · Cited by 114 · see citing works

Safety Monitoring in Clinical Trials

Yao, B., Zhu, L., Jiang, Q., et al. (2013) · Pharmaceutics · doi:10.3390/pharmaceutics5010094 · Cited by 113 · see citing works

A statistical approach to central monitoring of data quality in clinical trials

Venet, D., Doffagne, E., Burzykowski, T., Beckers, F., Tellier, Y., Genevois-Marlin, E., Becker, U., Bée, V., Wilson, V., Legrand, C., et al. (2012) · Clinical Trials · doi:10.1177/1740774512447898 · Cited by 108 · see citing works

Practical aspects of decision making in clinical trials: The coronary drug project as a case study

The Coronary Drug Project Research Group (1981) · Controlled Clinical Trials · doi:10.1016/0197-2456(81)90041-6 · Cited by 98 · see citing works

Introduction to Statistical Methods for Clinical Trials

Cook, T. D., & DeMets, D. L. (2007) · Chapman & Hall/CRC eBooks · doi:10.1201/9781420009965 · Cited by 96 · see citing works

Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study

Campbell, B. C. V., Mitchell, P. J., Churilov, L. P., et al. (2017) · International Journal of Stroke · doi:10.1177/1747493017733935 · Cited by 86 · see citing works

Data monitoring committees: Promoting best practices to address emerging challenges

Fleming, T. R., DeMets, D. L., Roe, M. T., Wittes, J. T., Calis, K. A., Vora, A. N., Meisel, A., Bain, R. P., Konstam, M. A., Pencina, M. J., et al. (2017) · Clinical Trials · doi:10.1177/1740774516688915 · Cited by 84 · see citing works

The New FDA Real-World Evidence Program to Support Development of Drugs and Biologics

Klonoff, D. C. (2019) · Journal of Diabetes Science and Technology · doi:10.1177/1932296819832661 · Cited by 77 · see citing works

Application of methods for central statistical monitoring in clinical trials

Kirkwood, A. A., Cox, T., & Hackshaw, A. (2013) · Clinical Trials · doi:10.1177/1740774513494504 · Cited by 75 · see citing works

Special population considerations and regulatory affairs for clinical research

Grimsrud, K., Sherwin, C. M. T., Constance, J. E., Tak, C. R., Zuppa, A. F., Spigarelli, M. G., & Mihalopoulos, N. L. (2015) · Clinical Research and Regulatory Affairs · doi:10.3109/10601333.2015.1001900 · Cited by 66 · see citing works

The impact of clinical trial monitoring approaches on data integrity and cost—a review of current literature

Olsen, R. H., Bihlet, A. R., Kalakou, F., et al. (2016) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-015-2004-y · Cited by 59 · see citing works

Data Monitoring Committees in Clinical Trials

Ellenberg, S. S., Fleming, T. R., & DeMets, D. L. (2019) · Wiley eBooks · doi:10.1002/9781119512684 · Cited by 52 · see citing works

Futility approaches to interim monitoring by data monitoring committees

DeMets, D. L. (2006) · Clinical Trials · doi:10.1177/1740774506073115 · Cited by 50 · see citing works

On Stopping a Randomized Clinical Trial for Futility

Herson, J., Buyse, M. E., & Wittes, J. T. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0140-7_5 · Cited by 46 · see citing works

Blinded Sample Size Reestimation with Negative Binomial Counts in Superiority and Non-inferiority Trials

Schmidli, H., & Friede, T. (2010) · Methods of Information in Medicine · doi:10.3414/me09-02-0060 · Cited by 46 · see citing works

Blinded sample size re‐estimation in superiority and noninferiority trials: bias versus variance in variance estimation

Friede, T., & Kieser, M. (2013) · Pharmaceutical Statistics · doi:10.1002/pst.1564 · Cited by 40 · see citing works

Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility

Walter, S. D., Han, H., Briel, M., & Guyatt, G. H. (2017) · Statistics in Medicine · doi:10.1002/sim.7242 · Cited by 33 · see citing works

Pro/con clinical debate: It is acceptable to stop large multicentre randomized controlled trials at interim analysis for futility. Pro: Futility stopping can speed up the development of effective treatments.

Schoenfeld, D., & Meade, M. O. (2004) · Critical Care · doi:10.1186/cc3013 · Cited by 32 · see citing works

Monitoring versus interim analysis of clinical trials: A perspective from the pharmaceutical industry

Enas, G. G., Dornseif, B. E., Sampson, C. B., et al. (1989) · Controlled Clinical Trials · doi:10.1016/0197-2456(89)90018-4 · Cited by 28 · see citing works

Sample Size Reestimation by Bayesian Prediction

Wang, M. (2007) · Biometrical Journal · doi:10.1002/bimj.200310273 · Cited by 28 · see citing works

Interim Analyses During Group Sequential Clinical Trials

Meurer, W. J., & Tolles, J. (2021) · JAMA · doi:10.1001/jama.2021.10174 · Cited by 26 · see citing works

Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial

MacDonald, T. M., Reginster, J., Littlejohn, T. W., Richard, D., Lheritier, K., Krammer, G., & Rebuli, R. (2008) · Journal of Hypertension · doi:10.1097/hjh.0b013e328302c9fe · Cited by 23 · see citing works

Blinded sample size reestimation in event‐driven clinical trials: Methods and an application in multiple sclerosis

Friede, T., Pohlmann, H., & Schmidli, H. (2019) · Pharmaceutical Statistics · doi:10.1002/pst.1927 · Cited by 19 · see citing works

Statistical design considerations for trials that study multiple indications

Kaizer, A. M., Koopmeiners, J. S., Chen, N., & Hobbs, B. P. (2020) · Statistical Methods in Medical Research · doi:10.1177/0962280220975187 · Cited by 18 · see citing works

Continuous covariate imbalance and conditional power for clinical trial interim analyses

Ciolino, J. D., Martin, R. H., Zhao, W., Jauch, E. C., Hill, M. D., & Palesch, Y. Y. (2014) · Contemporary Clinical Trials · doi:10.1016/j.cct.2014.02.007 · Cited by 16 · see citing works

Sample size re‐estimation in clinical trials

Wang, P., & Chow, S. (2021) · Statistics in Medicine · doi:10.1002/sim.9175 · Cited by 15 · see citing works

Participants’ perspectives on safety monitoring in clinical trials

Flynn, K. E., Kramer, J. M., Dombeck, C., & Weinfurt, K. P. (2013) · Clinical Trials · doi:10.1177/1740774513484394 · Cited by 12 · see citing works

Blinded and unblinded sample size reestimation in crossover trials balanced for period

Grayling, M. J., Mander, A., & Wason, J. M. S. (2018) · Biometrical Journal · doi:10.1002/bimj.201700092 · Cited by 11 · see citing works

Challenges of Decision Making Regarding Futility in a Randomized Trial

Yeatts, S. D., Martin, R., Coffey, C. S., et al. (2014) · Stroke · doi:10.1161/strokeaha.113.003925 · Cited by 9 · see citing works

Sample size re-estimation for pivotal clinical trials

Liu, Y., & Xu, H. (2020) · Contemporary Clinical Trials · doi:10.1016/j.cct.2020.106215 · Cited by 7 · see citing works

Bayesian and frequentist approaches to sequential monitoring for futility in oncology basket trials: A comparison of Simon’s two-stage design and Bayesian predictive probability monitoring with information sharing across baskets

Kaizer, A. M., Zabor, E. C., Nie, L., & Hobbs, B. P. (2022) · PLoS ONE · doi:10.1371/journal.pone.0272367 · Cited by 7 · see citing works

Sharing interim trial results by the Data Safety Monitoring Board with those responsible for the trial’s conduct and progress: a narrative review

Debono, V. B., Mbuagbaw, L. C. E., & Thabane, L. (2017) · Trials · doi:10.1186/s13063-017-1858-y · Cited by 6 · see citing works

Sample Size Reestimation by Bayesian Prediction

Wang, M. (2006) · Biometrical Journal · doi:10.1002/bimj.200510273 · 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

Interim decisions in oncology trials.

Yao, B., Zhang, K., Jemiai, Y., & Chang, D. D. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.e12530

Interim Analysis

Cleophas, T. J., & Zwinderman, A. H. (2016) · Springer eBooks · doi:10.1007/978-3-319-39586-9_8

Interim Analysis and Data Monitoring

Evansd, S. R., & Barry, W. T. (2018) · Springer Publishing Company eBooks · doi:10.1891/9780826168733.0031 · Cited by 1 · see citing works

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

Fernandes, R. M. F., van der Lee, J. H., & Offringa, M. (2009) · BMC Pediatrics · doi:10.1186/1471-2431-9-77 · Cited by 107 · see citing works

Should statisticians reporting to data monitoring committees be independent of the trial sponsor and leadership?

Ellenberg, S. S., & George, S. L. (2004) · Statistics in Medicine · doi:10.1002/sim.1784 · Cited by 33 · see citing works