PHARMACEUTICAL STATISTICS

Pharmaceut. Statist. 2004; 3: 155–156 (DOI:10.1002/pst.134)

Editorial

Welcome to this issue of Pharmaceutical Statistics.As always, we have a varied and interestingcollection of contributions which we hope youwill find useful.

Carpe diem, quam minimum credula postero

In her Viewpoint article Christy Chuang-Steinmakes clear how expensive and difficult it is tobring a successful drug to market. Some of thestatistics she quotes are quite disturbing: 50%failure rate during Phase III testing, $800 millionto take a new molecular entity from laboratory tomarket. As she says, statisticians have their part toplay in increasing the chances of success andhelping to reduce the costs and should aspire to beequal partners in the drug development process.

LOCF (leaves only complete fiction)?

In days of yore, before statisticians had computersto perform analysis of variance calculations, ittook weeks or months to analyse a large agricul-tural experiment. It was very important then thatthe designs used in trials had useful balanceproperties that simplified the formulae used inthe calculations (and also gave the design someoptimal properties). It was no wonder thattechniques were developed to ‘replace’ missingdata so that the balance properties of the designcould be retained. Now, however, with everincreasing computing power, designs can be moreflexible (lack balance if necessary) and analysesmore sophisticated. Missing data no longer needto be filled in as analyses of non-orthogonaldesigns are straightforward (for statisticians atleast). In pharmaceutical statistics we seem to have

regressed back to the ‘good old days’ of filling inmissing data to avoid a more sophisticatedanalysis. By this we mean the use of the methodof last observation carried forward (LOCF). Thisis used when longitudinal data are collected on apatient at specified clinic visits but the patientdrops out of the trial sometime before the finalvisit, and it is the data from the final visit thatconstitute the primary endpoint. As long as thereis at least one post-baseline data value on a subjectwith such (monotone) missing data, the lastobservation collected is used in place of themissing primary endpoint. In this issue we havetwo contributions from Craig Mallinckrodt andco-workers on the topic of LOCF. In the shorterof these, one conclusion is that ‘Practice shouldshift away from the use of LOCF’. Perhaps, afterreading these papers, you will agree with theauthors. If not, please think of sending in aViewpoint article in defence of LOCF.

Other main papers

Kit Roes writes in defence of the method ofdynamic allocation and discusses the recent CPMPdocument on adjustment for baseline covariates.You may or may not agree with Kit. If you have astrong opinion on this, we would again welcome aViewpoint contribution.

Early stopping in clinical trials, especially inoncology, is an attractive option. Murray Selwynand Susan Fish review some group sequentialmethods that use alpha spending functions andshow that trials based on these compare favour-ably with fixed sample size trials. Ian Bartonconsiders the apparent discrepancies between

Copyright # 2004 John Wiley & Sons, Ltd.

analyses based on individual patient data andsummary statistics that aim to determine therelationship between the risk of osteoporoticfracture and a surrogate measure.

Consultant’s Forum and Teacher’s Corner

We are sure that as an industry statistician youfind that one of your more common tasks is todetermine the sample size for an upcoming trial. Inthis issue we have two contributions on this topic.Steven Julious and Scott Patterson consider thesituation where a preliminary or pilot study isconducted with a view to doing a later definitivestudy. In Teacher’s Corner, Steven also gives ananswer to a question most of us have been askedby our clinical colleagues at some point in ourcareer.

Congratulations

The prize for the best paper written by a PSImember and published in Volume 2 was awardedto John Stevens for his joint paper with AnthonyO’Hagan and Paul Miller on a ‘Case study in theBayesian analysis of a cost-effectiveness trial in the

evaluation of health care technologies: depression’.The paper was chosen because it showed a goodpractical application of statistics in a relativelynew area for statisticians to be involved in. Thepaper covered sufficient theory, included a detailedpractical example and appended programmingcode. It also challenged some of the currentpractice of the application of statistics in this area.

Seize the day (or night)

Don’t forget that submissions to PharmaceuticalStatistics should now be made using our on-linesystem, available 24 hours a day, seven days aweek. The link you will need is http://pst-wiley.manuscriptcentral.com. We welcome ap-plied, short papers that relate to any stage of drugdevelopment and have relevance to statisticians inthe pharmaceutical industry.

We hope you enjoy this issue of PharmaceuticalStatistics.

Byron JonesChristy Chuang-Stein

Larry Furlong

Copyright # 2004 John Wiley & Sons, Ltd. Pharmaceut. Statist. 2004; 3: 155–156

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