Biopharmaceutical Applied Statistics Symposium: Volume 2 Biostatistical Analysis of Clinical Trials

251 Pages·2018·5.52 MB·English

by  Karl E. Peace

ICSA Book Series in Statistics
Series Editors:
Jiahua Chen · Ding-Geng (Din) Chen
Karl E. Peace
Ding-Geng Chen
Editors
Sandeep Menon
Biopharmaceutical
Applied Statistics
Symposium
Volume 2 Biostatistical Analysis of
Clinical Trials
ICSA Book Series in Statistics
Series editors
JiahuaChen,DepartmentofStatistics,UniversityofBritishColumbia,Vancouver,
Canada
Ding-Geng (Din) Chen, University of North Carolina, Chapel Hill, NC, USA
More information about this series at http://www.springer.com/series/13402
Karl E. Peace Ding-Geng Chen
(cid:129)
Sandeep Menon
Editors
Biopharmaceutical Applied
Statistics Symposium
Volume 2 Biostatistical Analysis of Clinical
Trials
123
Editors
KarlE. Peace Sandeep Menon
Jiann-Ping HsuCollege of Public Health BostonUniversity
Georgia SouthernUniversity Cambridge, MA, USA
Statesboro, GA,USA
Ding-GengChen
SchoolofSocialWork&GillingsSchoolof
GlobalPublic Health
University of NorthCarolina
ChapelHill, NC,USA
and
University of Pretoria
Pretoria, SouthAfrica
ISSN 2199-0980 ISSN 2199-0999 (electronic)
ICSABookSeries inStatistics
ISBN978-981-10-7825-5 ISBN978-981-10-7826-2 (eBook)
https://doi.org/10.1007/978-981-10-7826-2
LibraryofCongressControlNumber:2017964432
©SpringerNatureSingaporePteLtd.2018
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Preface
Currently,therearethreeVolumesoftheBASSBookSeries,spanning45chapters.
Chapters in this book are contributed by invited speakers at the annual meetings
of the Biopharmaceutical Applied Statistics Symposium (BASS). Volume 1 is
titled: Design of Clinical Trials and consists of 15 chapters; Volume 2 is titled
BiostatisticalAnalysisofClinicalTrialsandconsistsof12chapters;andVolume3
istitledPharmaceuticalApplicationsandconsistsof18chapters.Thethreevolumes
include the works of seventy authors or co-authors.
HistoryofBASS:BASSwasfoundedin1994,byDr.KarlE.Peace.Dr.Peace
is the Georgia Cancer Coalition Distinguished Scholar/Scientist, Professor of
Biostatistics,FoundingDirectoroftheCenterforBiostatistics,andSeniorResearch
ScientistintheJiann-PingCollegeofPublicHealthatGeorgiaSouthernUniversity.
Originally, there were three objectives of BASS. Since the first editor founded
the Journal of Biopharmaceutical Statistics (JBS) 3 years before founding BASS,
one of the original objectives was to invite BASS Speakers to create papers from
their BASS presentations and submit to JBS for review and publication. Ergo,
BASS wastobe asource ofpapers submitted toJBStoassistinthegrowth ofthe
new journal JBS. The additional two objectives were:
(cid:129) toprovideaforumforpharmaceuticalandmedicalresearchersandregulatorsto
sharetimelyandpertinentinformationconcerningtheapplicationofbiostatistics
in pharmaceutical environments; and most importantly,
(cid:129) to provide revenues to support graduate fellowships in biostatistics at the
MedicalCollegeofVirginia(MCV)andattheJiann-PingHsuCollegeofPublic
Health at Georgia Southern University (GSU).
After the JBS was on firm footing, the first objective was formally dropped. In
addition, the third objective was expanded to include potentially any graduate
program in biostatistics in the USA.
v
vi Preface
BASSI(1994)washeldattheHyattRegencyinOrlando,FL;BASSII–IIIwere
held at the Hilton Beach Resort, Inner Harbor, in San Diego, CA; BASS IV–VII
were held at the Hilton Oceanfront Resort Hotel, Palmetto Dunes, in Hilton Head
Island, SC; BASS VIII–XII were held at the Desoto Hilton; and BASS XIII–XVI
were held at the Mulberry Inn, both located in the Historic District of Savannah,
GA. BASS XVII was held at the Hilton Resort Hotel at Palmetto Dunes, Hilton
HeadIsland,SC.BASSXVIII–XIXwereheldattheMulberryInninSavannah.To
mark thetwentieth Anniversary BASS meeting, BASSXX was held in Orlando at
the Hilton Downtown Orlando Hotel. BASS XXI was held at the Holiday Inn
Crowne Plaza in Rockville, MD, whereas BASS XXII and XXIII were held at the
Radisson Hotel in Rockville, Maryland.
BASS XXIV (www.bassconference.org) was held at the Hotel Indigo in the
charminghistoricGeorgiacityofSavannah.Morethan360tutorialsand571-dayor
2-dayshortcourseshavebeenpresentedatBASS,bytheworld’sleadingauthorities
onapplicationsofbiostatisticalmethodsattendanttotheresearch,clinicaldevelop-
ment, and regulation of biopharmaceutical products. Presenters represent the bio-
pharmaceuticalindustry,academia,andgovernment,particularlytheNIHandFDA.
BASS is regarded as one of the premier conferences in the world. It has served
thestatistical,biopharmaceutical,andmedicalresearchcommunitiesforthepast24
yearsbyprovidingaforumfordistinguishedresearchersandscholarsinacademia,
governmentagencies,andindustriestoconductknowledgesharing,ideaexchange,
andcreativediscussionsofthemostup-to-dateinnovativeresearchandapplications
to medical and health care to enhance the health of general public, in addition to
providing support for graduate students in their biostatistics studies. Toward this
latterend,BASShasprovidedfinancialsupportfor75studentsincompletingtheir
Master or Doctorate degree in Biostatistics. In addition, BASS has provided
numerous travel grants to Doctorate-seeking students in Biostatistics to attend the
annual BASS meeting. This provides a unique opportunity for students to broaden
their education, particularly in the application of biostatistical design and analysis
methods, as well as networking opportunities with biostatisticians from Academia,
the Pharmaceutical Industry, and governmental agencies such as the FDA.
Volume II of the BASS Book Series, entitled Biostatistical Analysis of
Clinical Trials, consists of 12 chapters. Chapter 1 presents collaborative targeted
maximum likelihood estimation methods to assess causal effects in observational
studies.Chapter2discussestheuseofgeneralizedtestsinclinicaltrials.Chapter3
presents discrete time-to-event and score-based methods with application to a
composite endpoint for assessing evidence of disease activity-free. Chapter 4 dis-
cussesmethodsforimputingmissingdatausingasurrogatebiomarkerandpresents
an analysis of the incidence of endometrial hyperplasia. Chapter 5 deals with
advancing the interpretation of patient-reported outcomes. Chapter 6 provides a
primer on network meta-analysis with an example.
Chapter 7 presents methods for detecting safety signals among adverse events
reported in clinical trials. Chapter 8 provides methods for meta-analysis for rare
events reported in clinical trials. Chapter 9 provides a treatise on missing data.
Preface vii
Chapter 10 discusses Bayesian subgroup analysis using hierarchical models.
Chapter 11 presents a question-based approach to the analysis of safety data.
Finally,inChap.12,theanalysisoftwo-stageadaptiveseamlessclinicaltrialdesign
is presented.
We are indebted to all the presenters, program committee, attendees, and vol-
unteers who have contributed to the phenomenal success of BASS over its first 24
years, and to the publisher for expressing interest in and publishing the Series.
Statesboro, USA Karl E. Peace, Ph.D.
Jiann-Ping Hsu College of Public Health
Georgia Southern Univesity
Chapel Hill, USA/Pretoria, South Africa Ding-Geng Chen, Ph.D.
Professor, University of North Carolina
Extraordinary Professor, University of Pretoria
Cambridge, USA Sandeep Menon
Vice President and Head of Early
Clinical Development, Biostatistics
Contents
1 Collaborative Targeted Maximum Likelihood Estimation
to Assess Causal Effects in Observational Studies. . . . . . . . . . . . . . 1
Susan Gruber and Mark van der Laan
2 Generalized Tests in Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . 25
Stephan Ogenstad
3 Discrete Time-to-Event and Rank-Based Methods
with Application to Composite Endpoint for Assessing
Evidence of Disease Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Macaulay Okwuokenye
4 Imputing Missing Data Using a Surrogate Biomarker:
Analyzing the Incidence of Endometrial Hyperplasia . . . . . . . . . . . 57
P. Lim and H. Jiang
5 Advancing Interpretation of Patient-Reported Outcomes . . . . . . . . 69
Joseph C. Cappelleri and Andrew G. Bushmakin
6 Network Meta-analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Joseph C. Cappelleri and William L. Baker
7 Detecting Safety Signals Among Adverse Events
in Clinical Trials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Richard C. Zink
8 Meta-analysis for Rare Events in Clinical Trials. . . . . . . . . . . . . . . 127
Ding-Geng Chen and Karl E. Peace
9 Missing Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Steven A. Gilbert and Jared C. Christensen
ix
x Contents
10 Bayesian Subgroup Analysis with Hierarchical Models. . . . . . . . . . 175
Gene Pennello and Mark Rothmann
11 A Question-Based Approach to the Analysis of Safety Data . . . . . . 193
Melvin S. Munsaka
12 Analysis of Two-Stage Adaptive Trial Designs . . . . . . . . . . . . . . . . 217
Shein-Chung Chow and Min Lin
Index .... .... .... .... .... ..... .... .... .... .... .... ..... .... 243