Abstract
Internal pilot studies used for establishing the required sample size for a clinical trial part way through that trial are attractive when one is faced with difficulties in determining underlying variances or underlying event rates. By extrapolating a known curio of post-hoc sample size calculations, it is demonstrated how a sample size calculation may be obtained from a blind internal pilot that increases the study size even though, had a decision been made to stop the study and unblind it, enough information existed to reject the null hypothesis.
The questions of whether to continue recruiting and how much further to recruit may be considered. This will be influenced by the determination of the final (relative to the initial) study size determined from the internal pilot and the current perceived interest in the research question. If a study is stopped at the point of the recalculation, the reasons for the early stopping need to be carefully considered to decide if any bias may result. The decision to stop may be unconditional or conditional on the data. The two cases are distinguished through a variety of examples and their possible biases are considered.
Similar content being viewed by others
References
Wittes J, Brittain E. The role of internal pilot studies in increasing the efficiency of clinical trials. Stat Med. 1990;9:65–72.
Gould AL. Interim analyses for monitoring clinical trials that do not materially affect the Type I error rate. Stat Med. 1992;11:55–66.
Birkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. 1990;13:2455–2463.
Sandvik L, Erikssen J, Mowinckel P, Rødland EA. A method for determining the size of internal pilot studies. Stat Med. 1996;15:1587–1590.
Denne JS, Jennison C. Estimating the sample size for a t-test using an internal pilot. Stat Med. 1999;18:1575–1585.
Wittes J, Schabenberger O, Zucker D, Brittain E, Proschan M. Internal pilot studies I: type I error rate of the naive t-test. Stat Med. 1999;18:3481–3491.
Zucker DM, Wittes JT, Schabenberger O, Brittain E. Internal pilot studies II: comparison of various procedures. Stat Med. 1999;18:3493–3509.
Proschan MA, Hunsberger SA. Designed extension of studies based on conditional power. Biometrics. 1995;51:1315–1324.
Xamoterol in Severe Heart Failure Study Group. Xamoterol in severe heart failure. The Lancet. 1990;336:1–6.
Lehr R. Sixteen 5-squared over D-squared: a relation for crude sample size estimates. Stat Med. 1992;11:1099–1102.
Pocock SJ. Group sequential methods in the design and analysis of clinical trials. Biometrika. 1977;64:191–199.
Pocock SJ. Interim analyses for randomized clinical trials: the group sequential approach. Biometrics. 1982;38:153–162.
Smith R, Roberts I. An amnesty for unpublished trials. Br Med J. 1997;315:622.
Day S. Practical issues with internal pilot studies. Proceedings of the 15th meeting of the International Society for Clinical Biostatistics. Basle, 1994.
Day S. Optimal placebo response rates for comparing two binomial proportions. Stat Med. 1988;7:1187–1194.
Wiles A, Atkinson G, Huson L, Morse P, Struthers L. Good statistical practice in clinical research: guideline standard operating procedures. Drug Inf J. 1994;28:615–628.
North PM. Ensuring good statistical practice in clinical research: guidelines for standard operating procedures (an update). Drug Inf J. 1998;32:665–682.
Ellenberg S, Geller N, Simon R, Yusuf S (Eds.) Proceeding of the meeting on practical issues in data monitoring of clinical trials. Stat Med. 1993;12:415–616.
Peace KE, (Ed). Biopharmaceutical Sequential Statistical Applications. New York: Marcel Dekker; 1992.
Day S. Book review. Stat Med. 1993;12:2059.
Whitehead J. On being a statistician on a data and safety monitoring board. Stat Med. 1999;18:3425–3433.
Peace KE. Discussion for interim analysis and sample size reestimation. Drug Inf J. 1993;27:765–769.
Herson J, Wittes J. The use of interim analysis for sample size adjustment. Drug Inf J. 1993;27:753–760.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Day, S. Operational Difficulties with Internal Pilot Studies to Update Sample Size. Ther Innov Regul Sci 34, 461–468 (2000). https://doi.org/10.1177/009286150003400215
Published:
Issue Date:
DOI: https://doi.org/10.1177/009286150003400215