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In these cases, active controlled studies are conducted, and may be planned to demonstrate either superiority or equivalence\/non\u2010inferiority of the new drug over the standard therapy (active control). In the non\u2010inferiority study, an important aspect is the ability to detect an inferior drug (assay sensitivity). It has been suggested that assay sensitivity for a non\u2010inferiority study should be deduced from historical data, specifically placebo controlled studies with the standard therapy. The assessment of assay sensitivity may also be important in a superiority trial that fails to demonstrate a statistically significant difference between treatments, and the sponsor attempts to determine whether there is lack of inferiority as an alternative hypothesis for regulatory approval. This paper describes two methods of putative placebo analysis for assessing assay sensitivity in active controlled trials. One approach imputes a point estimate for the odds ratio (95 per cent confidence interval) for a new drug (T) compared to a placebo control (P). A Bayesian approach calculates the posterior probability that T is superior to P, or, that T is at least k per cent as good as the active control (A) and A is more effective than P. These methods are applied in two clinical\/regulatory settings: a phase III trial comparing docetaxel (Taxotere) to doxorubicin in metastatic breast cancer patients, and a phase III programme with two trials comparing enoxaparin (Lovenox) plus aspirin to unfractionated heparin plus aspirin in patients with unstable angina or non\u2010Q\u2010wave myocardial infarction. The methodologies presented in this paper were used in securing regulatory approval for docetaxel in the treatment of locally advanced or metastatic breast cancer after failure of prior chemotherapy, and for enoxaparin in the treatment of acute coronary syndrome. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/sim.1454","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T23:14:30Z","timestamp":1048029270000},"page":"941-952","source":"Crossref","is-referenced-by-count":34,"title":["The use of putative placebo in active control trials: two applications in a regulatory setting"],"prefix":"10.1002","volume":"22","author":[{"given":"Sylvain","family":"Durrleman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Chaikin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,2,21]]},"reference":[{"issue":"7","key":"e_1_2_1_2_2","first-page":"1037","article-title":"Sample size requirements for evaluating a conservative therapy","volume":"62","author":"Makuch R","year":"1978","journal-title":"Cancer Treatment Reports"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.2307\/2531438"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(82)90024-1"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.313.7048.36"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980815\/30)17:15\/16<1703::AID-SIM972>3.0.CO;2-G"},{"issue":"11","key":"e_1_2_1_7_2","first-page":"1061","article-title":"Treatment evaluation in active control studies","volume":"71","author":"Fleming TR","year":"1987","journal-title":"Cancer Treatment Reports"},{"key":"e_1_2_1_8_2","unstructured":"International Conference on Harmonisation.E10: Choice of control group in clinical trials. 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