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Preface vii
Computing
To take advantage of the computer, one needs a good statistical package. We use Stata,
which is available from the Stata Corporation in College Station, Texas. We find this
statistical package to be one of the best on the market today; it is user-friendly, accu-
rate, powerful, reasonably priced, and works on a number of different platforms, in-
cluding Windows, Unix, and Macintosh. Furthermore, the output from this package is
acceptable to the Federal Drug Administration in New Drug Approval submissions.
Other packages are available, and this book can be supplemented by any one of them.
In this second edition, we also present output from SAS and Minitab in the Further Ap-
plications section of each chapter. We strongly recommend that some statistical pack-
age be used.
Some of the review exercises in the text require the use of the computer. To help
the reader, we have included the data sets used in these exercises both in Appendix B
and on a CD at the back of the book. The CD contains each data set in two different for-
mats: an ASCII file (the "raw" suffix) and a Stata file (the "dta" suffix). There are also
many exercises that do not require the computer. As always, active learning yields bet-
ter results than passive observation. To this end, we cannot stress enough the importance
of the review exercises, and urge the reader to attempt as many as time permits.
Acknowledgements
A debt of gratitude is owed a number of people: Harvard University President Derek
Bok for providing the support which got this book off the ground, Dr. Michael K. Martin
for calculating Tables A.3 through A.8 in Appendix A, and John-Paul Pagano for
viii Preface
assisting in the editing of the first edition. We thank the individuals who reviewed the
manuscript: Rick Chappell, University of Wisconsin; Dr. Todd G. Nick, University of
Mississippi Medical Center; Al Bartolucci, University of Alabama at Birmingham;
Bruce E. Trumbo, California State University, Hayward; James Godbold, The Mount
Sinai School of Medicine of New York University; and Maureen Lahiff, University of
California, Berkeley. Our thanks to the teaching assistants who have helped us teach the
course and who have made many valuable suggestions. Probably the most deserving of
thanks are the students who have taken the course over the years and who have toler-
ated us as we learned how to teach it. We are still learning.
Marcello Pagano
Kimberlee Gauvreau
Boston, Massachusetts
Contents
l Introduction
1. 1 Overview of the Text 2
1.2 Review Exercises 5
Bibliography 6
2 Data Presentation 7
2.1 Types of Numerical Data 7
2.1.1 Nominal Data 7
2.1.2 Ordinal Data 9
2.1 .3 Ranked Data 10
2.1.4 Discrete Data 10
2.1.5 Continuous Data 11
2.2 Tables 11
2.2.1 Frequency Distributions 12
2.2.2 Relative Frequency 13
2.3 Graphs 15
2.3.1 Bar Charts 15
2.3.2 Histograms 16
2.3.3 Frequency Polygons 18
2.3.4 One-Way Scatter Plots 20
2.3.5 Box Plots 21
2.3 .6 Two-Way Scatter Plots 22
2.3.7 Line Graphs 22
2.4 Further Applications 24
2.5 Review Exercises 30
Bibliography 36
ix
x Contents
5 Life Tables 97
5. 7 Computation of the Life Table 97
5.1.1 Column 1 97
5.1.2 Column 2 99
Contents xi
6 Probability 125
6. 7 Operations on Events and Probability 125
6.2 Conditional Probability 129
6.3 Bayes' Theorem 1 131
6.4 Diagnostic Tests 135
6.4.1 Sensitivity and Specificity 136
6.4.2 Applications of Bayes' Theorem 136
6.4.3 ROC Curves 140
6.4.4 Calculation of Prevalence 141
6.5 The Relative Risk and the Odds Ratio 144
6.6 Further Applications 149
6.7 Review Exercises 155
Bibliography 160
J7 Correlation 398
17. 1 The Two-Way Scatter Plot 398
17.2 Pearson's Correlation Coefficient 400
17.3 Spearman's Rank Correlation Coefficient 404
17.4 Further Applications 407
17.5 Review Exercises 412
Bibliography 414
Appendix A
Tables A-1
Appendix B
Data Sets B-1
Index 1-1
Introduction
In 1903, H. G. Wells hypothesized that statistical thinking would one day be as neces-
sary for good citizenship as the ability to read and write. Statistics do play an important
role in many decision-making processes. Before a new drug can be marketed, for in-
stance, the United States Food and Drug Administration requires that it be subjected to
a clinical trial, an experimental study involving human subjects. The data from this
study must be compiled and analyzed to determine whether the drug is not only effec-
tive, but safe. In addition, the U.S. government's decisions regarding Social Security
and public health programs rely in part on predictions about the longevity of the na-
tion's population; consequently, it must be able to predict the number of years that each
individual will live. Many other issues need to be addressed as well. Where should a
government invest its resources if it wishes to reduce infant mortality? Does the use of
a seat belt or an air bag decrease the chance of death in a motor vehicle accident? Should
a mastectomy always be recommended to a patient with breast cancer? What factors in-
crease the risk that an individual will develop coronary heart disease? To answer these
questions and others, we rely on the methods of biostatistics.
The study of statistics explores the collection, organization, analysis, and inter-
pretation of numerical data. The concepts of statistics may be applied to a number of
fields that include business, psychology, and agriculture. When the focus is on the bio-
logical and health sciences, we use the term biostatistics.
Historically, statistics have been used to tell a story with numbers. Numbers often
communicate ideas more succinctly than do words. The message carried by the follow-
ing data is quite clear, for instance. In 1979, 48 persons in Japan, 34 in Switzerland, 52
in Canada, 58 in Israel, 21 in Sweden, 42 in Germany, 8 in England, and 10,728 in the
United States were killed by handguns [1]. The power of these numbers is obvious; the
point would be made even if we were to correct for differences in population size.
As a second example, consider the following quotation, taken from an editorial in
The Boston Globe [2]:
In this case, a great deal of information is contained in only three numbers: 120, 20, and
40. The statistics provide some insight into the consequences of differing attitudes to-
ward family planning.
In both these examples, the numbers provide a concise summary of certain as-
pects of the situation being studied. Surely the numerical explanation of the handgun
data is more illuminating than if we had been told that some people got killed in Japan,
fewer in Switzerland, more in Canada, still more in Israel, but far fewer in Sweden, and
so forth. Both examples deal with very complex situations, yet the numbers convey the
essential information. Of course, no matter how powerful, no statistic will convince
everyone that a given conclusion is true. The handgun data are often brushed away with
the aphorism "Guns don't kill people, people do." This should not be surprising; after
all, there are still members in the Flat Earth Society. The aim of a biostatistical study is
to provide the numbers that contain information about a certain situation and to present
them in such a way that valid interpretations are possible.
If we wish to study the effects of a new diet, we might begin by measuring the changes
in body mass over time for all individuals who have been placed on the diet. Similarly,
if we wanted to investigate the success of a certain therapy for treating prostate can-
cer, we would record the lengths of time that men treated with this therapy survive be-
yond diagnosis with the disease. These collections of numbers, however, can display a
great deal of variability and are generally not very informative until we start combin-
ing them in some way. Descriptive statistics are methods for organizing and summa-
rizing a set of data that help us to describe the attributes of a group or population. In
Chapter 2, we examine tabular and graphical descriptive techniques. The graphical ca-
pabilities of computers have made this type of summarization more feasible than in the
past, and a whole new mode of presentation is available for even the most modest
analyses.
Chapter 3 goes beyond the graphical techniques presented in Chapter 2 and in-
troduces numerical summary measures. By definition, a summary captures only a par-
ticular aspect of the data being studied; consequently, it is important to have an idea of
how well the summary represents the set of measurements as a whole. For example, we
might wish to know how long AIDS patients survive after diagnosis with one of the op-
portunistic infections that characterize the disease. If we calculate an average survival
time, is this average then representative of all patients? Furthermore, how useful would
the measure be for planning future health service needs? Chapter 3 investigates de-
scriptive techniques that help us to answer questions such as these.
I.I Overview of the Text 3
Data that take on only two distinct values require special attention. In the health
sciences, one of the most common examples of this type of data is the categorization of
being either alive or dead. If we denote the former state by 0 and the latter by 1, we are
able to classify a group of individuals using these numbers and then to average the re-
sults. In this way, we can summarize the mortality associated with the group. Chapter
4 deals exclusively with measurements that assume only two values. The notion of di-
viding a group into smaller subgroups or classes based on a characteristic such as age
or gender is introduced as well. We might wish to study the mortality of females sepa-
rately from that of males, for example. Finally, this chapter investigates techniques that
allow us to make valid comparisons among groups that may differ substantially in com-
position.
Chapter 5 introduces the life table, one of the most important techniques available
for study in the health sciences. Life tables are used by public health professionals to
characterize the well-being of a population, and by insurance companies to predict how
long a particular individual will live. In this chapter, the study of mortality begun in
Chapter 4 is extended to incorporate the actual time to death for each individual; this
results in a more refined analysis. Knowing these times to death also provides a basis
for calculating the survival curve for a population. This measure of longevity is used
frequently in clinical trials designed to study the effects of various drugs and surgical
treatments on survival time.
In summary, the first five chapters of the text demonstrate that the extraction of
important information from a collection of numbers is not precluded by the variability
among them. Despite this variability, the data often exhibit a certain regularity as well.
For example, if we look at the annual mortality rates of teenagers in the United States
for each of the last ten years, we do not see much variation in the numbers. Is this just
a coincidence, or is it indicative of a natural underlying stability in the mortality rate?
To answer questions such as this, we need to study the principles of probability.
Probability theory resides within what is known as an axiomatic system: we start
with some basic truths and then build up a logical system around them. In its purest
form, the system has no practical value. Its practicality comes from knowing how to use
the theory to yield useful approximations. An analogy can be drawn with geometry, a
subject that most students are exposed to relatively early in their schooling. Although it
is impossible for an ideal straight line to exist other than in our imaginations, that has
not stopped us from constructing some wonderful buildings based on geometric calcu-
lations. The same is true of probability theory: although it is not practical in its pure
form, its basic principles-which we investigate in Chapter 6---can be applied to pro-
vide a means of quantifying uncertainty.
One important application of probability theory arises in diagnostic testing. Un-
certainty is present because, despite their manufacturers' claims, no available tests are
perfect. Consequently, there are a number of important questions that must be answered.
For instance, can we conclude that every blood sample that tests positive for HIV actu-
ally harbors the virus? Furthermore, all the units in the Red Cross blood supply have
tested negative for HIV; does this mean that there are no contaminated samples? If there
are contaminated samples, how many might there be? To address questions such as
these, we must rely on the average or long-term behavior of the diagnostic tests; prob-
ability theory allows us to quantify this behavior.
4 Chapter I Introduction
Chapter 7 extends the notion of probability and introduces some common proba-
bility distributions. These mathematical models are useful as a basis for the methods
studied in the remainder of the text.
The early chapters of this book focus on the variability that exists in a collection
of numbers. Subsequent chapters move on to another form of variability-the variabil-
ity that arises when we draw a sample of observations from a much larger population.
Suppose that we would like to know whether a new drug is effective in treating high
blood pressure. Since the population of all people in the world who have high blood
pressure is very large, it is extremely implausible that we would have either the time or
the resources necessary to examine every person. In other situations, the population may
include future patients; we might want to know how individuals who will ultimately de-
velop a certain disease as well as those who currently have it will react to a new treat-
ment. To answer these types of questions, it is common to select a sample from the
population of interest and, on the basis of this sample, infer what would happen to the
group as a whole.
If we choose two different samples, it is unlikely that we will end up with pre-
cisely the same sets of numbers. Similarly, if we study a group of children with con-
genital heart disease in Boston, we will get different results than if we study a group of
children in Rome. Despite this difference, we would like to be able to use one or both
of the samples to draw some conclusion about the entire population of children with
congenital heart disease. The remainder of the text is concerned with the topic of sta-
tistical inference.
Chapter 8 investigates the properties of the sample mean or average when re-
peated samples are drawn from a population, thus introducing an important concept
known as the central limit theorem. This theorem provides a foundation for quantifying
the uncertainty associated with the inferences being made.
For a study to be of any practical value, we must be able to extrapolate its find-
ings to a larger group or population. To this end, confidence intervals and hypothesis
testing are introduced in Chapters 9 and 10. These techniques are essentially methods
for drawing a conclusion about the population we have sampled, while at the same time
having some knowledge of the likelihood that the conclusion is incorrect. These ideas
are first applied to the mean of a single population. For instance, we might wish to es-
timate the mean concentration of a certain pollutant in a reservoir supplying water to
the surrounding area, and then determine whether the true mean level is higher than the
maximum concentration allowed by the Environmental Protection Agency. In Chapter
11, the theory is extended to the comparison of two population means; it is further gen-
eralized to the comparison of three or more means in Chapter 12. Chapter 13 continues
the development of hypothesis testing concepts, but introduces techniques that allow the
relaxation of some of the assumptions necessary to carry out the tests. Chapters 14, 15,
and 16 develop inferential methods that can be applied to enumerated data or counts-
such as the numbers of cases of sudden infant death syndrome among children put to
sleep in various positions-rather than continuous measurements.
Inference can also be used to explore the relationships among a number of different
attributes. If a full-term baby whose gestational age is 39 weeks is born weighing 4 kilo-
grams, or 8.8 pounds, no one will be surprised. If the baby's gestational age is only 22
Discovering Diverse Content Through
Random Scribd Documents
Lieve, oude Lieveling,
Je Judy.
25 September.
J. Abbott.
17 October.
Wanneer het heele zwembassin met citroenvla gevuld zou zijn, zou
dan iemand die zwemmen kan, zich boven de vla kunnen houden of
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Wij hadden vanavond aan tafel citroenvla als dessert en kwamen er
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Nog twee andere kwesties werden aan tafel besproken.
A. Hoe moeten de kamers in
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beweerden dat ze vierkant
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Geloof je ook niet?
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is en iemand daar middenin
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en waar zal het glas beginnen
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Hoe meer je er over
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je het.
Nu zie je eens, wat een diepzinnige onderwerpen er bij ons bij net
eten behandeld worden en dan zeggen ze nog: als de katjes muizen,
mauwen ze niet.
Heb ik je al over de verkiezingen gesproken? Het is al drie weken
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ketelmuziek gaven.
Wij zijn nu heel gewichtige personages in No. „258”. Een groot deel
van Sallie's glorie straalt ook op Julia's onwaardig hoofd en op het
mijne: het is een heele eer met de Presidente samen te wonen!
Bonne nuit, cher ami!
Acceptez mes compliments.
Très respectueux
Je suis
Votre Judy.
12 November.
Je J. A.
Zaterdag.
Wil je niet eens weten hoe ik er uitzie? Hier heb je een kiek van ons
drietjes, die Leonora Fenton genomen heeft.
Dat meisje in het wit, dat lacht, is Sallie, en de lange met haar neus
in de lucht is Julia en dat kleintje met hangend haar is Judy. Ze ziet er
in werkelijkheid beter uit, maar de zon scheen net in haar gezicht.
„Stone Gate”
Worcester, Mass.
31 December.
Je Judy Abbott.
P.S. Zou je het heel, heel erg vinden, mijn liefste lieveling, wanneer
ik geen Groote Schrijfster werd, maar alleen een heel gewoon meisje
bleef?
6.30 Zaterdag.
Liefste Vadertje.
We waren eigenlijk vandaag van plan naar de stad te gaan, maar
we hadden geen rekening met het weer gehouden: het stortregent
nu. Ik houd van den winter wanneer hij ook werkelijk winter is met
sneeuw en ijs, maar niet wanneer het regent. Julia's model-oom
kwam haar vanmiddag opzoeken. Hij bracht vijf pond bonbons mee!!
Je ziet, er is ook wel eens een voordeeltje aan verbonden, om met
Julia samen te wonen. Ons gebabbel scheen hem te amuseeren en hij
besloot een lateren trein te nemen en eerst met ons samen thee te
drinken. Het was vreeselijk lastig voor ons om daartoe verlof te
krijgen. Het is al heel moeilijk om een vader of grootvader bij ons te
mogen hebben en een oom—nu, dat is weer een graadje erger. Broers
en neven zijn heelemaal contrabande! Julia moest voor een notaris
den eed afleggen, dat hij werkelijk haar oom was en toen heeft een
klerk daarvan dadelijk een certificaat opgemaakt. (Weet ik niet een
heeleboel van rechtsgeleerdheid af?) En dan betwijfel ik nog hard, of
we Oom Jervie wel bij ons hadden mogen houden, als die lieve
menschen gezien hadden, hoe jong en knap hij er uitziet.
Lieve deugd,
wat regent het!
Als we vanavond
naar de kapel
willen, zullen we
er heen moeten
zwemmen!
Dag
lieveling
,
Je Judy.
20 Januari.
P.S. Iets weet ik toch heel beslist: ik kom niet uit China!
4 Februari.
Je Judy.
5 Maart.
Nacht Lieveling!
Je Judy.
P.S. Ik keek net op de kalender. Het is de 28ste.
Nog eens P.S. Ik zag vandaag een tramconducteur met één blauw
en één bruin oog. Zou dat geen prachtig kenteeken zijn voor een
schurk in een detective roman?
7 April.
Judy.
10 April.
Judy.
11 April.
Liefste lieveling.
Zeg, wil je me vergeven, dat ik je gisteren zoo'n naren brief
schreef? Toen ik hem op de bus had gedaan, had ik er al weer spijt
van en ik vroeg hem terug, maar die vervelende brievenbesteller
wilde hem er niet meer uithalen.
Het is nu middernacht. Ik lig uren lang wakker door die ellendige
gedachte, dat ik zoo'n wurm, zoo'n duizendpootig wurm ben. (Dat is
het ergste scheldwoord, dat ik voor me zelf bedenken kan). Ik heb
heel voorzichtig de deur van onze werkkamer dicht gemaakt om
Sallie en Julia niet te wekken en zit nu op een vel papier, dat ik uit
mijn geschiedenis-dictaatcahier heb gescheurd, aan jou te schrijven.
Ik wou je zeggen dat ik het zoo naar vind, dat ik je dien chèque
zoo plompweg heb teruggestuurd. Ik weet dat je het heel lief hebt
bedoeld en je bent een schat, dat je je zoo'n moeite geeft voor zoo'n
dom kind als ik ben. Ik had hem je natuurlijk wel terug moeten
sturen, maar heel anders dan ik het deed.
Maar in elk geval moest ik hem terugsturen. Het is bij mij zoo iets
heel anders dan bij de andere meisjes. Die hebben vaders en
moeders en tantes en ooms, maar ik heb heelemaal geen familie, ik
heb niemand, niets. Ik stel me wel graag voor, dat jij zoo'n beetje
familie van me bent, omdat ik dat zoo'n prettig gevoel vind, maar ik
weet natuurlijk heel goed, dat dat maar onzin is. Ik sta heelemaal
alleen op de wereld, en ik moet me schrap zetten, om den strijd met
het leven te aanvaarden. O, ik word koud als ik daaraan denk. Ik
durf er dikwijls niet aan denken en daarom fantaseer ik zooveel,
maar je begrijpt ook wel, dat ik niet meer mag aannemen dan ik al
doe, omdat ik je later alles wil terugbetalen en zelfs als ik werkelijk
nog eens een groote schrijfster word, zal het toch moeilijk zijn om
zoo'n vreeselijk groote schuld af te lossen.
Ik hou heel veel van mooie kleeren en hoeden, maar ik mag mijn
toekomst niet verpanden door ze nu te koopen.
Wees er niet boos over, dat ik daar zoo ruw over spreek. Ik heb de
afschuwelijke gewoonte om alles impulsief neer te schrijven,
wanneer ik het denk, om er dan later berouw over te hebben als de
brief al weg is en ik hem niet meer kan verscheuren. Maar al lijk ik
soms ook ruw en ondankbaar, ik meen het toch nooit. In mijn hart
dank ik je altijd voor het vrije leven, waarin je me geplaatst hebt en
de onafhankelijkheid, die ik door jou zal verkrijgen. Mijn jeugd was
één lange sleur, die ik met al mijn oproerige gedachten niet kon
verbreken en nu voel ik me elken dag zoo gelukkig, dat ik nu, na dat
heele jaar op College, soms nog niet kan gelooven dat ik niet droom.
Ik voel me als een heldin in een verhaaltje!
Het is nu kwart over twee. Ik ga op mijn teenen naar de bus om
dezen brief nog even te posten. Je zult hem dus precies een post na
dien anderen krijgen en je kan dus gelukkig niet lang boos op me
zijn.
Nacht lieveling!
Judy.
4 Mei.
Dat is eerst eens roem! Toen ben ik naar het tentje gegaan en heb
me daar heelemaal met spiritus afgewreven en een citroenkwast
gedronken. Je ziet, dat we altijd aan onze gezondheid denken. Het is
heel verdienstelijk, als je een spel voor je klas wint, want de klas, die
de meeste spelen wint, krijgt dat jaar den wisselbeker. Dit jaar
kregen de Juniores hem met zeven spelen in hun voordeel. Het
comité bood alle winners in het gymnastieklokaal een diner aan. We
kregen kreeft, en chocolade-ijs in den vorm van korfballen.
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