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Response Surface Methodology: 1966–l988

a b a
Raymond H. Myers , André I. Khuri & Walter H. Carter
a
Department of Statistics, Virginia Polytechnic Institute and State University, Blacksburg, VA,
24061
b
Department of Statistics, University of Florida, Gainesville, FL, 32611
c
Department of Biostatistics, Medical College of Virginia, Richmond, VA, 23219

To cite this article: Raymond H. Myers , André I. Khuri & Walter H. Carter (1989) Response Surface Methodology: 1966–l988,
Technometrics, 31:2, 137-157, DOI: 10.1080/00401706.1989.10488509

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 TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2

Response Surface Methodology: 1966-l 988

Raymond H. Myers Andr6 I. Khuri Walter H. Carter, Jr.

Department of Statistics Department of Statistics Department of Biostatistics

Virginia Polytechnic Institute University of Florida Medical College of Virginia
and State University Gainesville, FL 32611 Richmond, VA 23219
Blacksburg, VA 24061

Response sarfxe methodology (RSM) is a collection of tools developed in the 1950s for the
purpose of determining optimum operating conditions in applications in the chemical industry.
This artic!e reviews the progrrss of RS;\l m the cwneral arcas of experimental design and
analysis and indicates how its role has been affected by adwnccs in other fields of applied
statistics. Current areas of research in RShI are highli~!ltsd. and areas for future ressJrch
are discussed.

KEY LVORDS: Experimental design: First-order model: Optimum conditions: Second-order

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model; Scquenti:ll strategy

1. INTRODUCTION ers not on finding optimum response but on finding

regions where there is demonstrated improvement in
In the November 1966issue of Techrzometrics, “.A
response over that achieved bq’ current operating
Review of Response Surface Methodolo_gy: A Lit-
conditions. This gives rise to the inev-itable applica-
erature Survey,” by Hill and Hunter appeared. That
tions in the chemical and processing fields and the
particular review emphasized practical applications
historical attraction to the subject by Technometrics
in the chemical and processing fields and featured an
readers. Our intent in this article is to provide a
excellent bibliography. In the December 1975 issue
review of important developments in RSM. with our
of Biometrics. “A Review of Response Surface definition being confined to that of a collection of
MethodologyFrom a Biometric Viewpoint.” by Mead
tools in desigtl or datu analysis that enhnrlce the e-v-
and Pike appeared. Emphasis was on biological ap-
pioration of a region of design variables it1 one or
plications. and a much broader definition of response more resporues. We will emphasize developments in
surface methodology (RSM) was made than that of the statistics literature that have appearedsince 1966
the Hill and Hunter paper. but will make reference to some pre-1966work vvhen
Hill and Hunter stated that RSM began with the
historical perspective is necessary.
work of Box and Wilson (1951).Mead and Pike moved
The experimental strategy and analysis in RSM
back the origin of RSM to include the‘use of “re-
revolves around the assumption that a response 17is
sponsecurves” dating back into the 1930s.In reality.
a function of a set of design variables xi. x2, ..
there are diverse notions as to what is the proper list
xi and that the function can be approximated in some
of topics to be included under the response-surface
region of the x’s by a polynomial model. Prominent
umbrella. This confusion is causedin part by the very
amongthe models considered are the first-order model
general name response surface. It is interesting that
all too many subject-matter scientists, many of whom ty = pi, + P[.x, - .‘. A /JI;.Yk (1.1)
are experienced in the use of statistical tools, are not
aware of the term resporzse surface annlysis or of the and the second-order model
problems it addresses.
There is no question that the motivation for the
work by Box and his coauthors was the general and
perhaps ancient problem of planning and analyzing
experiments in a search for desirable conditions on (1.2)
a set of controllable (or design) variables. *.desira-
ble” often being defined more strictly as those con- Generally, the assumption of common error variance
ditions that give rise to optimum response. In recent CT?is made. sugpestingthe useof ordinary leastsquares
Years,much-emphasishas been placed by pructition- for estimation of coefficients. In certain instances in

137
 138 RAYMOND H. MYERS, ANDRt I. KHURI,
the following, we will deal specifically with nonlinear
models.
We should make the intentions of the article clear.
Technometrics readers include academic as well as
industrial statisticians and engineers. Historical per-
spective is always important when a review is pre-
sented. It provides a link to the past and inspiration
to potential researchers in the field. But an addi-
tional. and perhaps the most important, purpose of
this article is to offer something to users. For expe-
rienced practitioners, we must provide a thorough
review. For those who are less experienced, we must
be convincing that RSM has something to offer.
2. RESPONSE SURFACE DESIGN
In this section, we deal with several aspects of
response surface designs, beginning with the “where
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we were” status of response surface design in the
mid-1960s. Thus some historical perspective is given.
We discuss specific design classes with heavy em-
phasis on composite designs. Due to their historical
importance, the property of rotatability and the con-
cept of protection against model misspecification are
discussedearly in the article. In addition, other items
include less general topics as designs for nonlinear
models, robust designs, designs for estimating the
slope of a responsesurface, and designs for the mix-
ture problem.
2.1 Status of Response Surface Design in the
Mid-1960s
Among the many important works that preceded
Hill and Hunter (1966), three are noteworthy here.
The first was the important article by Box and Wilson
(1951) in which the notion of composite designs was
introduced. The introduction of the “star portion”
to augment a two-level factorial array was done to
allow for efficient estimation of quadratic terms in
the second-order model of Equation (1.2). This class
of designs allows flexibility. This would later prove
very beneficial as more sophisticated properties and
criteria evolved. More details regarding the com-
posite designs are given in Section 2.2.
Sharing the sphere of influence with Box and Wil-
son is the Box and Hunter (1957) article. Emphasis
was placed on judging a design on the basis of pre-
dictiorz variance> var J/o’. This was a vital contri-
bution, since it underscored very early that a single
number may not be enough information when com-
paring designs. The distribution of var J/a? over the
spaceof the design variables was explored. A natural
and easily attainable property was that of rotatahiliry ,
which requires that the variance of a predicted value
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
AND WALTER H. CARTER, JR.
remain constant at points that are equidistant from
the design center. It is rare when a heavy price is
paid to achieve near-rotatability. Rotatability in the
case of first-order models is attainable with standard
orthogonal arrays that have many other important
properties. In the caseof a second-ordermodel. com-
posite designs and other designs can be made to be
rotatable very easily (see Sec. 2.2).
The historical importance of the property evolved
naturally from the need to achieve stability in pre-
diction variance. Too many designs have very un-
stable prediction variance close to the design perim-
eter. Rotatability was a first step. and, unlike many
other criteria, it could be put to use immediately with
standard designs. Obviously, in experiments with
mixtures in which a simplex region is important, ro-
tatability is less appealing. Moreover. in early ex-
ploratory phases of RSM when the learning process
about the design variables is in its infancy, the ro-
tatability property is certainly not important and may
even be compromised in favor of other desirable de-
sign features. Nevertheless. it is always a good idea
to preserve some degreeof rotatability wherever pos-
sible. Recently, two measures of rotatability were
introduced. The first one: introduced by Khuri (1988),
is a quantitative measure expressible as a percentage
with the value 100 attained when the design is ro-
tatable. The second measure, introduced by Draper
and Guttman (19SS),provides information about the
overall shape of the variance contours for symmet-
rical second-order designs.
A third very influential piece of work of the 1950s
and 1960swas by Box and Draper (1939, 1963). It
was an introduction of the notion of robustness of
an RSM design to model misspecification. although
the word “robustness” was not used in this regard
until later. Convincing arguments are made that not
only can bias due to model misspecification not be
ignored but that, if there is even a modest amount
of misspecification, the user must seriously consider
it in choice of design.
The fundamental philosophy of the Box-Draper
work centered around the consideration of the av-
erage weighted mean squared error
w( x)E[j( x) - g(x)]: dx,
where j(s) is the fitted polynomial of order d, and
s(x) is a model of order d, > d, containing unknown
parameters and is regarded as the “true” mean re-
sponse. or at least it can be viewed as the model that
one choosesto protect against. Here, R is the region
of interest in the design variables-that is, a region
in which it is important for Q to predict well. K is the
 reciprocal of the volume of R, h’ is the total number
of observations, W(X) is a weight function. and 0’ is
the error variance. The expression J divides into
the sum of the weighted variance and squared bias.
averaged over the region R. In the formulation
presented here, the minimum J design cannot be
achieved, and evidence was put forth that a robust
strategy of design choice is one that comes close to
minimizing the bias portion of J. Similar work deal-
ing in regions of interest other than spherical was
given by Draper and Lawrence (1965) and Draper
and Guttman (1986).
Although much of the foundation of very funda-
mental work was established by that cited in the fore-
going, the appetite of the practical user of RSM had
beensatisfied by the establishment of families of use-
ful experimental designs for first-order and second-
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order models. In the first-order case, the need for
orthogonal designswas motivated by Box and Wilson
(1951), Box (952), and an excellent book edited by
Davies (1954). Specific design classes, two-level fac-
torial and fractional factorial designs, were made
available by Plackett and Burman (1946) and Box
andHunter (1961a.b).For second-ordermodels, many
subject-matter scientists and engineers have a work-
ing knowledge of the family of central composite
designs (CCD’s) and a class of special three-level
designsby Box and Behnken (1960). Another im-
portant pre-1966 contribution came from Hartley
(1959), who made an effort to create a more eco-
nomical or small composite design.
In the following sections, we provide reviews of
what we feel are important RSM design topics, be-
ginning with the mid-1960s. In addition to historical
chronology, we attempt to provide potential users
with practical advice, as well as reference for further
edification.
2.2 The Central Composite Design and
Alternate Design Plans
The CCD is a special caseof the classof composite
designsin which the construction consists of three
Portions, (a) the 2’ vertices of a cube (or a fraction
Of these vertexes), (bj the 2k vertexes of a cross-
PolYtopeor “star” or axial portion with parameter
(y,and (c) a chosen number, nO,of center runs. The
Points in (b) essentially form an augmentation that
‘ePresentsa one-factor-at-a-time portion designedto
Provideestimation of the B,).the pure quadratic terms
in Equation (1.2). The factorial-design levels are cen-
tered and scaled to design units with rl being the
factorial levels and CYbeing the axial level. In large
Part, the appeal of the CCD is derived from its Aex-
ibility and its utility as a design plan for sequential
experimentation. The factorial portion and center
runs serve as a preliminary phase from which one
may fit a first-order model and yet gain evidence
regarding the importance of pure quadratic contri-
bution. Textbooks in RSM by Box and Draper (1987),
Khuri and Cornell (1987), and Myers (1976) pro-
vided a fundamental look at the CCD.
Much of the flexibility of the CCD is derived from
the user’s choice of (Yand Q. There are many criteria
used for the choice of these parameters.
Choice of (Y. For CY> k”‘. the axial points are
further from the designcenter than the factorial points.
A value cy= (F)l”. where Fis the number of factorial
points. guarantees rotatability. Other criteria, how-
ever, such as robustness to model misspecification
(Sec. 2.1), qualitv estimation of the slope (Sec. 2.8),
robustness to outliers (Sec. 3.6), generalized vari-
ance of model coefficients (Sec. 2.5), and orthogonal
blocking are among the important considerations for
choice of cyconsidered by researchers.
Note that the experimental region often dictates
the value of a. If the region is spherical? a natural
upper bound for (Yis fi. There are many situations.
however, in which the user wishes to explore a region
that is strictly cuboidal. In this case, (Y = 1.0 is an
appropriate choice.
Choice of nO. The choice of the number of center
runs is a vital ingredient for the CCD. An early rec-
ommendation by Box and Hunter (1957)was to choose
12”for which u/ziform irlformation or ufliform preci-
sion is achieved; this property provides approxi-
mately a uniform value of var J(s) inside a sphere
of a specific radius. There has long been confusion
among users about what is gained by this property.
however. The original Box-Hunter definition of uni-
form precision requires IZ”to be chosen such that var
j(x) is approximately constant inside a sphere of
radius 1.0, with the metric of design units requiring
scaling so that the second moment o.f the design t’ari-
ables is unit)l. Unfortunately. this does not seempar-
ticularly pleasing, since it does not exert control or
produce stability in prediction variance at a distance
that approaches the radius at the perimeter of the
design region. The practical user should read Draper
(1982) and Box and Draper (1987) for general dis-
cussions regarding the number of center runs for
composite designs.
2.3 Orthogonal Blocking
The CCD is the second-order family that is rich in
candidate designsthat block orthogorlally. The latter
describes a condition in which regressioncoefficients
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 140 RAYMOND H. MYERS, ANDRi I. KHURI,
are orthogonal to block effects and thus the analysis
can be conducted without ambiguous interpretation.
Box and Hunter (1957, 1961a.h)developed the gen-
eral conditions that give rise to orthogonal blocking
in the second-order case. The Box-Bchnken design
also gives rise to orthogonal blocking in some situ-
ations. The books by Khuri and Cornell (1987). Box
and Draper (1987), and Myers (1976) give the user
real-life examples in which blocking is part of the
design plan.
2.4 Other Second-Order Designs
Although the central composite remains the sec-
ond-order designfamily that is most often used. there
are other second-order design classes that are at-
tractive in various circumstances. We earlier made
reference to the class of Box-Behnken designs. The
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Box-Behnken designs can be very useful in casesin
which it is important that three levels be used. In
addition to the original Box-Behnken reference, Box
and Draper (1987) and Khuri and Cornell (1987) give
illustrations using the Box-Behnken design. In the
paragraphs that follow, we review some of the other
second-order designs that appeared after the mid-
1960s.
Hoke (1974) developed a class of economical sec-
ond-order designs based on irregular fractions of the
3” factorial plan. These fractions are based on sets
of partially balancedarrays and are compared to Box-
Behnken and other competing designs. Roquemore
(1976) developed a family of second-order designs
called Ilq’Drid desigrzsfor k = 3, 4, 6, and 7 that are
either saturated or near-saturated and have some
similarities to the CCD. The design for k variables
is constructed by augmenting a (k - I)-dimensional
CCD with an additional column in the design matrix.
The values for the additional column are chosen to
achieve certain design symmetries.
The Hoke and hybrid designsare by no means the
only choices that are available when one seeks a
saturated or near-saturatedsecond-orderdesign. Notz
(1981) suggested a method of constructing designs
that are very efficient in terms of generalized vari-
ance-that is. D-efficiency (seeSec. 2.5). His designs
are saturated and are constructed from the 3“ lattice.
Box and Draper (1974) produced practical designs
that are saturated and efficient from a generalized
variance standpoint. Similar developmentswere given
by Mitchell and Bayne (197S), Welch (19S2), and
others. During the 1970s and early 1980s. much of
the work that resulted in the development of new
second-order designsrevolved around the concept of
D-optimality and D-eticiency (see Sec. 3.5). From
a historical point of view, these developments served
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
AND WALTER H. CARTER, JR.
to produce usable designs that deserved merit from
the design optimality standpoint. It is important for
the potential user to note the price that one often
pays by using a strictly saturated design, either for a
first-order or second-order model. The major short-
coming of a saturated design is derived from poor
coverage of the region of interest.
2.5 Application of Criteria Dealing With
Optimal-Design Theory
The important development of optimal-design the-
ory in the field of experimental design emerged fol-
lowing World War II. It was motivated by various
authors, including Elfving (1953, 1955, 1959). Cher-
noff (1953), Kiefer (1958, 1959, 1960, 1962a,b), and
Kiefer and Wolfowitz (1959, 1960). Kiefer, in par-
ticular, was instrumental in providing the mathe-
matical groundwork for optimal-design theory. Ac-
tually. the origin of this theory can be traced back
to an article by Smith (1918), who considered dif-
ferent design configurations for polynomial models
up to the sixth degree. Interestingly enough, he ex-
amined cases in which the error variance was not
constant within the experimental region. Some earl!
work in this area was done by Wald (1943) and Mood
(1946).
Optimal-design theory has clearly become an im-
portant component in the general development of
experimental design for the caseof regressionmodels.
Although no one can reasonably deny the contri-
bution and impact of optimal-design theory. there
are some who believe that its application in RShf
design work should be made with extreme caution.
The main characteristics of this theory are the per-
ception of a design as a probability measure with
heavy emphasis on variance reduction with regard to
the fitted model. Bias plays a lesserrole, unlike what
we see in the work of Box and Draper.
The most prominent design criterion is D-opti-
mality, the minimization of the generalized variance
of the model coefficients. This criterion has received
a great deal of attention, as evidenced by the nu-
merous articles written about it. The review articles
by St. John and Draper (1975), Ash and Hedayat
(1978), and Atkinson (1982) contained many refer-
enceson D-optimality. Another design criterion that
is closely related to D-optimality is G-optimality: in
which the maximum prediction variance over the ex-
perimental region is minimum. other variance-re-
lated criteria include A-optimality and E-optimality
[see Pazman (19X6,chap. 4) for a description of these
criteria]. Silvey (lYSO), Bandemer (19SO),and At-
kinson (1952) provided recent surveys of optimal ex-
perimental designs.
The well-known equivalencetheorem of Kiefer and
 RESPONSE SURFACE METHODOLOGY:
Wolfowitz (1960) led to the development of a prac-
tical algorithm for the construction of a D-optimal
design (Fedorov 1972, chap. 2: Wynn 1970). More
attention. however, has been given to the construc-
tion of a D,,-optimal design. This is the traditional
responsesurface design consisting of N experimental
runs, where h! is fixed, for which the determinant of
the information matrix. X’ X. for the fitted model
is maximum. Several algorithms are available for the
construction of D,-optimal designs. The DETMAX
algorithm by Mitchell (1974) and the one by Fedorov
(1972, pp. 160-165) generate a sequence of h:-point
designs vvith nondecreasing values of /X’ X/ for a
given A;. An improvement over Mitchell’s algorithm
was presented by Galil and Kiefer (1980), who de-
veloped a family of computer-search methods for
finding optimum designs. A review of algorithms for
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constructing DN-optimal designswas given by Cook
and Nachtsheim (1980) (seealso Johnson and Nacht-
sheim 1983). Lucas (1974. 1976. 1977) used the D-
and G-efficiencies of a design. as defined by Atwood
(1969). to evaluate the performance of some tradi-
tional response surface designs for second-order
models.
One important criticism of optimal-design theory
is that it is set within a rigid framework governed by
a set of assumptions that may not be very realistic.
This has prompted Box. Hunter, and Hunter (1978)
to state that “in recent years the study of optimal
design has become separated from real esperimen-
tation with the predictable consequencethat its iim-
itations have not been stressed. or, often, even re-
alized” (p. 472).
As we indicated earlier. one traditional approach
in RSM development involves the concentration on
bias suspected of being present in the fitted model.
This is the basis for the Box-Draper criterion dis-
cussedin Section 2.1. The bias criterion, however.
provides protection against a specific form of model
inadequacv according to what we postulate as the
“true mod-el.” Kiefer (1975. pp. 284-286) criticized
certain aspectsof the preoccupation with bias, point-
ing out examples in which the variance criterion is
compromised for the sake of the bias criterion. Both
Kiefer and Box agree that design selection should be
guidedby more than one criterion. “no single simple
Prescription can be expected to yield satisfactory de-
signsin all, or even most, applications” (Kiefer 1975.
P. 256): see also Box (1982, sec. 7).
2.6 RSM Design Robustness
As we indicated in Section 2.1, the first notion of
RSh’ldesign robustness appearedin the \\ork of Box
and Draper (1959, 1Y63) dealing with protection
1966-1988 141
against model underspecification. It formalized. in
an RSM setting. the notion of proper placing of the
design points it7 j’~~rn rhe hozrnria~~~sf the region of
interest when under-specification is a concern. Al-
though specifics in the Box and Draper work dealt
with spherical regions. Draper and Lawrence (1965)
applied the Box and Draper approach to generate
designs that are robust to model inadequacies in the
case of cuboidal regions.
Aside from model misspecification. RSM design
robustness includes the following categories: (a) ro-
bustness to outliers in the data, (b) robustness to
errors in the design levels, and (c) designs for ex-
trapolation under conditions of model misspecifica-
tions.
From a point of view of motivation. the article by
Box and Draper (1975) would appear to have been
very timely. We highly recommend that any serious
practitioner of RSM read it carefully. This work linked
the awareness of outlic~+sto notions of RSM exper-
imental designs. Design properties were sought that
resulted in “minimal impact” of outliers in the re-
sulting data. The reader of the Box and Draper ar-
ticle will be reminded that in many cases an exper-
iment is designed for many different purposes. There
is an implication that optimal designs should not be
sought nearlv as often as designs that are “good” in
many areas; that is, we seek cornp~of?risedesigns.
This same opinion is expressedby many others (e.g..
Atkinson 19S2; Kiefer 1975).
Herzberg and Andrews (1976) dealt with optimal
designsunder nonoptimal conditions such as missing
observations and the presence of outliers. In an ar-
ticle that considered protection against model mis-
specification and outliers simultaneously. Draper and
Herzberg (1979)dealt with an integratedmeansquared
error criterion much like that of Box and Draper
(1959. 1963).
A related notion of robustness deals with errors
in the factor levels. Vuchkov and Boyadjieva (1983)
considered this problem and attempted to determine
design families that are robust. The interested reader
should first read the article by Box (1963) in which
the effect of errors in factor levels was considered in
both first-order and second-order models. Although
no specific design criteria are considered in Box’s
article, it is an excellent account of the extent of the
damage when errors in design variables occur.
Finally, we deal in a type of design property that
somemay not generallyclassifyasl.oblarrzess--nameI!!.
,
designs that are resistmt to errors in extrapolation.
This is particularly important in RSM work. since a
response surface is often used bv necessity for ex-
trapolation purposes. Draper anb Herzberg (lY73.
lY7Y) discussed designs that are robust rn this sense
under the settings of first-order and second-order
I
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 142 RAYMOND H. MYERS, ANDFii I. KHURI,
fitted models. It is assumed that one’s ability to cx-
trapolate is influenced by the esistence of higher-
order terms in the true structure.
One important note of caution should be made to
any user or potential user of RSM. A design may
indeed be nearly optimal in one sense (say D-opti-
mality) but far from optimal with respect to another
criterion. For example. designs that are capable of
protecting the user against model inadequacy due to
higher-order terms are not necessarily going to be
capable of detecting the need for these additional
model terms. Often all that can be expected of an
RSM design is one that enjoys a “steady” perfor-
mance in several criteria that are important to the
user.
2.7 Design of Mixture Experiments
From the early pioneering work in the late 19%
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by Scheffe (1958). techniques in the use of mixture
designs became important to users of RSM. A mix-
ture experiment is one in which the responsedepends
on the relative proportions of the ingredients in the
mixture. These experiments are characterized as fol-
lows: If x, (i = 1, 2, . . , k) represents the pro-
portion of the ith component in a k factor combi-
nation. then for each experimental run 0 5 x:, 5 1
(i = 1.3, . . , k) and cf=, x, = 1. The development
of designs and the analysis of data collected under
these constraints has been the subject of much re-
search. Mixture designs have enjoyed extensive ap-
plication in chemicals, petroleum. foods. tobaccos,
and many other areas. Indeed. the particular area
has been the subject of two reviews by Cornell (1973,
1979), mentioned prominently in two additional re-
views by Mead and Pike (1975) and Steinberg and
Hunter (1984), and the subject of a book by Cornell
(1981). The reader is referred to these works for a
complete bibliography on the subject. Some impor-
tant works not contained in these bibliographies and
those which have appeared since their publication
will be reviewed briefly in this section.
Snee (1981) used the gasoline-blending problem
to illustrate some practical problems that occur when
considering mixture experiments. Attention is fo-
cused on the design of blending studies and appro-
priate models for analysis, as well as the use to which
the fitted model is put. Often constraints apart from
the standard ones are placed on mixture components.
Piepel (1983) used the definition of the centroid
as the center of mass or volume of the region. He de-
veloped an algorithm to calculate centroids of vari-
ous dimensional faces of the constraint region as well
as the centroid of the (k - l)-dimensional simplex.
Crosier (1984) proposed a transformation to pseudo-
components to reduce the ill-conditioning created by
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
AND WALTER H. CARTER, JR.
the constraints. Conditions are given that can be used
to determine when the use of the transformation is
preferable to that of other transformations.
Aitchison and Bacon-Shone (1984) showed that
the constant sum constraint-that is, cf=, -u! = l-
can be removed by a log ratio transformation, i, =
log(x,/xk) (i = 1. 2, . . . . k - 1). When this is done,
the modeled expected response can be expressedas
a polynomial in the z,. Since the 2, can be varied
independently, the polynomial can include all terms
of appropriate degree.
St. John (1984) pointed out that, due to the con-
straints placed on the independent variables, mixture
problems are particularly prone to difficulties caused
by ill-conditioning of the X matrix. Illustrations were
given with several published data sets. In some in-
stances standard remedial techniques were useful,
whereas in other casesit was necessaryto use ridge
regression to improve the conditioning of X’ X.
2.8 Designs for the Slope
In many applications of RSM, good estimation of
the derivatives of the response function may be as
important or perhaps more important than estima-
tion of mean response. Certainly, the computation
of a stationary point in a second-order analysis or
the use of gradient techniques-for example, steep-
est ascent or ridge analysis-depends heavily on the
partial derivatives of the estimated responsefunction
with respect to the design variables. Since designs
that attain certain properties in 9 (estimated re-
sponse) do not enjoy the same properties for the
estimated derivatives (slopes), it is important for the
user to consider experimental designs that are con-
structed with the derivatives in mind.
Atkinson (1970) considered designsfor estimation
of the slope at a fixed point with the responsefunc-
tion being of order 1. The criterion used is the ex-
pected mean squared error for a directional deriva-
tive averaged over all possible directions. Murty and
Studden (1972) considered polynomial-regression
models with the criterion being the variance of an
estimated slope at a fLvedpoint and averaged over
an interval.
Hader and Park (1978) extended the notion of
rotatability to cover the slope for the caseof second-
order models. They cataloged designs that result in
slope rotatability; that is. the variance of the esti-
mated derivatives is constant for all points equidis-
tant from the design center. Myers and Lahoda (1975)
extended the Box-Draper integrated mean squared
error criterion under model misspeciflcation to cover
sets of parametric functions, with the slope being the
primary application.
 RESPONSE SURFACE
Mukerjee and Huda (1985) developed designs as-
sociated with minimum variance of the estimated
slope maximized over all points in the factor space
for second-order and third-order polynomial models
over a spherical region.
2.9 Designs for Special Goals
Designs for Nonhear Models. A nonlinear model
is a model of the form y = f(x. 0) + E, where x =
(Xl. x2. . . 1xk)’ is a vector of design variables. 0
=: (O,, t?‘, . . , 0,)’ is a vector of unknown param-
eters. E is a random error, and f(x. 0) is a known
function nonlinear with respect to at least one ele-
ment of 0. Nonlinear models have not received a
great deal of attention in RSM, even though they
hate many applications in Several areas, particularly,
in biological and chemical sciences.
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The main design criterion for nonlinear models is
the D-optimality criterion. which actually applies to
a linearized form of the nonlinear model (Box and
Lucas 1959). More specifically, if f(x, 0) is approx-
imately linear in 0 in a neighborhood of 0 = Oo,then
a design D is chosen so that the determinant !F’(D,
0,,) F(D, 0,)i is maximum, where F( D, 0,) is an N
x: p matrix whose (i, j)th element is
fi, = ““d;; 0) ) the initial design. Dykstra (1966) and Gaylor and
J R=H,,
i = 1,2 , 1N, j= 1,3,. ,p,
In the preceding, af/aH, denotes the partial deriva-
tive off with respect to 8,, x, is the value of x in the
ith experimental run. and h’ is the number of ex-
perimental runs. An optimal design obtained under
this criterion is more appropriately called a locally
D-optimal design, a terminology used by Chernoff
(1.953).A similar design criterion is available if the
interest is in only a subset of the parameter vector
0 (see Box 19711Hill and Hunter 1973).
Unlike D-optimal designsfor linear models. those
for nonlinear models depend on the unknown values
Of 0. This is an unappealing characteristic of nonlin-
ear models and was most appropriately depicted by
Cochran (1973): “You tell me the value of 0 and I
promise to design the best experiment for estimating
0.” There are several procedures to remedy, or at
least alleviate, the problem of design dependency.
One is a sequential procedure beginning with an in-
itial guess, 0” (see Box and Hunter 1965). Silvey
(1980) discussedthe problem of design dependency
on 0 using several examples of nonlinear models.
An alternative strategy for dealing with design de-
pendency is to adopt a Bayesian approach. Zacks
(1977) considered maximizing the expected value of
the determinant jF’( D, 0) F(D, 0)l with respect to
someprior distribution of 0. Bayes sequential designs
METHODOLOGY: 1966-1988 143
can also be obtained using procedures analogous to
those proposed by Box and Hunter.
The dependency of the optimal nonlinear design
on the parameter vector 0 is less severe if the model
is partially nonlinear. By that we mean that some
elements of 0 appear linearly in the model. but others
appear nonlinearly (see Hill 1980: Khuri 1954).
Design Augmentation. Design augmentation is
an increasingly important component in the pro-
gression of RSM research. It is important for the
potential user of RSM to understand the “sequential
spirit” of RSM. In a large percentage of RShl ap-
plications more than one stage of experimentation
and analysis is required. The notion of moving from
one experimental region to another and planning an
experiment in sequenceoften becomes necessaryin
real RSM situations. Quite often, additional exper-
imental runs are taken after an experiment has been
carried out. This usually occurs when information
obtained in one stage is used to plan the next stage.
Moreover. there might be a need to gain more in-
formation about the response in certain parts of the
region that are not adequately covered by the initial
design.
As a sequential plan evolves, the additonal runs
are chosen in a manner that remedies. or repairs,
Merrill (196s) augmented a nonorthogonal designfor
fitting a first-order model with additional runs to re-
duce multicollinearity effects among the design vari-
ables. Covey-Crump and Silvey (1970) and Mayer
and Hendrickson (1973) adopted the maximization
of jX’ XI criterion for the selection of the additional
experimental runs. where X is the matrix of design
Irariables associated with the linear model for both
the initial design and the augmented runs. In Covey-
Crump and Silvey (1970), the augmented design
points were selectedfrom a spherical region, whereas
in Mayer and Hendrickson (1973), the augmented
design points were constrained by cost considera-
tions. Dykstra (1971) described a method for aug-
menting the initial designwith additional points taken
one at a time. Hebble and Mitchell (1973) follo\vcd
a similar procedure. except that the entire region of
interest, insteadof a set of candidatepoints. is searched
for the next design point. Wynn (1970) showed that
this process leads in the limit to a D-optimal design.
Evans (1979) used the simplex search technique to
add several points simultaneously under the maxi-
mum of 1X’ X1 criterion.
Dcsigtu 10 Itlcrease the Polymerof the Lack-o!-Fit
Test. Checking the adequacy of a fitted model 1san
important consideration in RSM. Draper and Herz-
berg (1971) provided some insight into the nature of
hypotheses that can be tested by the lack-of-fit test
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 144 RAYMOND H. MYERS, ANDRE I. KHURI,
when replicate observations are available at one or
more design points. Equally important is the ability
to detect lack of fit in a model at an early stage of
the experimental process. This necessitates the use
of a design that can induce a certain degree of sen-
sitivity in the lack-of-fit test. To accomplish this, the
designshould be selectedso as to maximize the power
of the associated lack-of-fit test. Unfortunately, de-
signs chosen under this criterion depend on the un-
known parameters of the true model. Several ap-
proacheswere considered to overcome this problem.
Atkinson (1972) used designs that are D-optimal for
the precise estimation of the true model’s parameters
that are not included in the fitted model. These de-
signs, however, may provide poor estimates of the
unknown parameters of the fitted model. Atkinson
and Fedorov (1975) suggested procedures to deal
with this problem. A maximin procedure was adopted
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by Jones and Mitchell (1978) to develop additional
designcriteria to detect model inadequacy. This work
prompted Morris and Mitchell (1953) to obtain de-
signsto detect the presenceof two-factor interactions
among several two-level factors when fitting a first-
order model.
3. RESPONSE SURFACE ANALYSIS
Hill and Hunter (1966) outlined four steps as part
of standard procedure in a responsesurface analysis.
We think they are worth repeating here. They are:
(a) perform a statistically designed experiment, (b)
estimate the coefficients in the responsesurface equa-
tion, (c) check on the adequacy of the equation (via
a lack-of-fit test). and (d) study the response surface
in the region of interest. We plan to consider step d
in this section.
The purpose of an RSM analysis is to answer cer-
tain general questions regarding the nature of the
response function in some region of interest. Deter-
mining whether the system contains a maximum or
minimum or is a saddle system may be very important
to the experimenter. On the other hand, the exis-
tence of a ridge system may indicate the need for
further experimentation in another region. In some
situations. response surface analysis serves as more
than merely an empirical device. It can lead to what
Hill and Hunter (1966) called an “elucidation of an
underlying mechanism” (p. 571) and thus uncover
theoretical information.
A distinction should be made between analyses
whose goals are to esplore the response surface as
indicated previously and that in which the major goal
is estimation of optimum conditions. The method of
steepest ascent remains a viable technique for se-
quentially moving toward the optimum response. See
Davies (19%). Myers (1976), Khuri and Cornell
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
AND WALTER H. CARTER, JR.
(1957), and Box and Draper (19S7) for details and
examples. Brooks and Mickey (1961) and Myers and
Khuri (1979) discussed strategy in steepest ascent.
In Section -C,we produce evidence that the use of
RSM is expanding into many areas. Indeed, data-
analysis procedures in general are expanding. We can
thank, in part at least, Japanesescientists, who have
successfully communicated to us the need for exper-
imental design at the research-and-developmentlevel
as a successful supplement to quality control and
process control. The Japanese industrial engineer
Genichi Taguchi (Taguchi 1986;Taguchi and Wu 19SO)
proposed methodology for product improvement that
has attracted many practitioners in this country. The
Taguchi approachdiffers from RSM in important ways.
Proponents of RSM assume an underlying model (a
local approximation) that can include system cur-
vature and interaction, and they design the experi-
ment accordingly. Taguchi recommended the use of
an orthogonal array (often a Plackett-Burman de-
sign) and benefits from a muin-efSrcts model to de-
termine the treatment combination that is most likely
to produce product improvement. Focus is on i/n-
provement and not optimization. RSM. on the other
hand. affords the user the wealth of model-building
techniques and model-based methods for finding op-
timum conditions or conditions that produce a par-
ticular target response. The Taguchi approach gen-
erally ignores interaction among the factors. Although
many feel as if the goals of the Taguchi work can
better be served through the use of more rigorous
statistical methods. there is much to be learned from
the Taguchi approach. He has made users in this
country aware of the need to include svslein or pro-
cess varinbility as part of the response. As a result,
the inevitable nonconstancy of variance is not ig-
nored. By the very nature of his method. he has
reminded us that sequential experimentation is often
the most effective way to explore an experimental
region.
One useful procedure in a second-order response
surface analysis is ridge analysis. introduced by Hoer1
(1959) and formalized by Draper (1963). The method
is discussed with examples by Khuri and Cornell
(1957), Box and Draper (1987), and Myers (1976).
Hoer1 (1985) gave a historical, almost anecdotal ac-
count of his father’s development of ridge analysis.
It has been our observation that, in practical RSM
problems, occasions in which the stationary point
produces a satisfactorv result are rare. As a result.
some type of constrained optimization like ridge
analysis is often indicated. Most users-for example.
engineers, biologists. and so forth- would certainly
prefer not to draw conclusions from response-con-
tour plots for cases in which k 2 2. Smith (1976)
related situations in which ridge analysis is mislead-
 RESPONSE SLJRFACE METHODOLOGY:
ing. Khuri and h’Iyers (1979) offered modifications
to ridge analysis in casesin which the design is not
nearly rotatable.
3.1 Multiresponse Analysis
In many experimental situations, a number of re-
sponsesare measured for each setting of a group of
design variables. Examples of multiresponse SitUa-
tions are numerous. Ziegel and Gorman (1980) gave
an interesting exposition of the use of multiresponse
data for studying kinetic models in the petroleum
industry. The area of foods and other consumer-
product research also represents a challenge because
of the need almost always to study many responses.
Typical studies require panel-type responses or
‘*scores” on many features of the product. The re-
view by Hill and Hunter (1966) listed several ex-
amples of multiresponse experiments and is perhaps
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the first article in the statistical literature to direct
attention to their important applications.
Subsequentworks on this subject have stressedthe
utility of analyzing multiresponse data by means of
multivariate techniques that take into account inter-
relations among the responses. For example, the
modelsthat represent the responsesmay have several
parameters in common. It would. therefore, make
senseto combine information from all the responses
to estimate these parameters. The method intro-
ducedby Box and Draper (1965) can be convenientIS
used for this purpose. They showed that increased
precision on the parameter estimate can be obtained
by using data from all responses.Certainly a situation
in which multiresponse analysis is desirable is in the
area of simultaneous optimization of several re-
sponses,which will be reviewed later in this section.
Unfortunately, multiresponse analysis is not as de-
veloped as its single-response counterpart. It is still
relatively new, and its utility has yet to be fully ap-
preciated (see Sec. 4j. This is mainly attributed to
the fact that computer software is practically non-
existent in this area.
Multiresponse Estimation. Box and Draper (1965)
developeda method to estimate the parameter vector
P in a general multiresponse model. The responses
were assumedto be normallv distributed and to have
a variance-covariance matrix. 2, considered con-
stant for the various runs within the experimental
regiOn. Box and Draper used a Bavesian argument
bY considering a noninformative prior distribution
for P and 2. Estimates of the elements of p were
then obtained by maximizing the marginal posterior
densitv of p. This method is known as the Box-
Draper estimation criterion. It applies to linear as
“ell as nonlinear models.
Box, Hunter, MacGregor, and Erjavec (1973) cau-
1966-1988 145
tioned that the Box-Draper estimation criterion can
lead to meaningless results when exact linear rela-
tionships exist among the responses. They also pro-
posed an eigenvalueanalysisfor the detection of these
relationships.
Further problems associated with the use of the
Box-Draper estimation criterion were considered by
McLean, Pritchard. Bacon, and Downie (1979). Box.
Draper, and Hunter (1970) and Stewart and Soren-
sen (1981) discussedapplications of the criterion when
some of the observations are missing. More recently,
Bates and Watts (1985) proposed a new computing
method for the determination of the parameter es-
timates using this criterion.
Des@ of Experiments for Multiresponse Situa-
tions. This is an important aspect of multiresponse
analysis, yet it is probably the least developed. In a
multiresponse situation, the choice of design should
be based. on a criterion that involves all the re-
sponses. Draper and Hunter (1966, 1967) obtained
design criteria for parameter estimation for general
multiresponse models. These criteria, however, re-
quire knoaledge of C, the variance-covariance ma-
trix for the I’ responses. Fedorov (1977) introduced
an algorithm for the construction of a D-optimal de-
sign for a linear multiresponse model using a pro-
cedure whereby design points are chosen sequen-
tially. Fedorov’s algorithm also requires knowledge
of 2. Recently, Wijesinha and Khuri (1987) intro-
duced a modification of Fedorov’s algorithm that can
be used when 2; is not known.
Multiresponse Optimization. Any scientist or en-
gineer learning about RSM will realize that in most
processesor scientific systems any experimental op-
timization problem is a multivariate one. Conditions
that are optimal for one response may be far from
optimal or even physically impractical for the other
responses.
Graphical methods were used early in the history
of RSM development. By superimposing response
contours and visually searching for a common region
where the responsesachieve near optimal values (if
such a region exists), a practitioner might be able to
somehow arrive at a location (or locations) of a
“compromised” optimum. Lind, Goldin, and Hick-
man (1960) used this procedure to obtain operating
conditions for maximizing the yield and minimizing
the cost of a certain antibiotic. Obviously, this pro-
cedure is difficult. if not impossible, to apply when
the number of design variables exceedsthree. Myers
and Carter (1973) introduced an algorithm for de-
termining conditions on the design variables that
maximize a prinmr~-response function subject to the
condition that a secondary,-resporlse function not ex-
ceed a certain value. Biles (1975) extended this con-
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 146 RAYMOND H. MYERS, ANDRi
cept of constrained optimization by placing bounds
on the values of sever4 secondary-response func-
tions.
A different optimization approach based on the
concept of utility or desirability was followed by Har-
rington (1965) and Derringer and Suich (19%)). In
this approac:h, each response function undergoes a
certain transformation into a desirability function, 4.
such that 0 514 5 1. The choice of the transformation
depends on a subjective judgment concerning the
importance ((or desirability) of the corresponding re-
sponse values. A measure of the overall desirability
of the responsesis obtained by combining the indi-
vidual desirability functions through the use of a geo-
metric mean More recently. Khuri and Conlon (1981)
introduced a procedure for the simultaneous opti-
mization of responsesthat are represented by linear
multiresponse models. A distance function is chosen
that measures the overall closeness of the response
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functions to achieving their respective optimal values
at the same set of operating conditions. The latter is
referred to as an i&al optimum. Optimum operating
conditions are then derived by minimizing this dis-
tance function over the experimental region.
3.2 Point and Interval Estimation of
Surface Properties
In the typical analysis of a second-degreeresponse
surface, one is interested in (a) the location of the
stationary point, (b) the response at the stationary
point, (c) the characterization of the stationary point
(i.e.. as a point of masimum or minimum response
or a saddle point). and (d) the contours of constant
response. One can write the true second-order re-
sponse equation as ‘1 = /Y,, + x’B + x’Bx. where s
= (x,, X’. . ) xc)‘, j3 = (,h’!, /I,. . . . . /Ii)‘, and
B is a symmetric matrix containing diagonal elements
that are pure second-order coefficients and whose ij
element is /;‘,/2. The nature of the stationary point
can be ascertained by considering the matrix B. If B
is a positive (negative) definite matrix. then the sta-
tionary point is a point of minimum (maximum) re-
sponse. If B is an indefinite matrix. the stationary
point is a saddle point. From this, it follows that the
eigenvalues of B are important to the proper de-
scription of the stationary point.
Many users of RSM allow conc!usions to be drawn
concerning the nature of a response surface and the
location of optimum response without taking into
account the distributional properties of the estimtrterf
attributes of the underlying response surface. Al-
though the distribution of these quantities has not
been considered directly, efforts have been made to
develop interval estimates. Box and Hunter (1954)
used a version of Fieller‘s theorem to develop a lOO(1
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
I. KHURI, AND WALTER H. CARTER, JR
- N)C& confidence region for the location of the
stationary point. The construction of a confidence
interval around the response at the stationary point
of the true surface has only recently been a subject
of interest in the statistical literature. Khuri and Con-
lon (1981) gave an expression for the bounds of such
an interval conditional on the estimated location of
the stationary point. Carter, Chinchilli, Campbell,
and Wampler (1983) report on the development of
a conservative, nonconditional interval for the re-
sponse at the stationary point. Stablein, Carter, and
Wampler (1983) extended the methodology devel-
oped by Box and Hunter (1954) to obtain a confi-
dence region about the location of the stationary
point in the presence of constraints. Carter. Chin-
chilli. Myers, and Campbell (1986) illustrated this
methodology for constructing confidenceintervals for
the eigenvalues of B and considered the implications
of having such an interval contain 0 on the interpre-
tation of the analysis. Interest is often focused on
the estimated contours of constant response. This is
consistent with the notion of learning where in the
design region an improved response is to be found
rather than searching for an optimum. Carter, Chin-
chilli, Wilson, Campbell, Kessler. and Carchman
(1986) and Box and Draper (1987, pp. 134,135) dealt
with the construction of a confidence region around
a contour of a given response.
3.3 Use of Alternate Models
There are many typical RSM situations in which
the user can make use of known information con-
cerning the distribution of the observed response.
Examples of such responsevariates are survival time.
proportion of experimental units assignedto a given
treatment group responding in a predetermined way,
and count data. To the extent that a continuous sym-
metric distribution can be made to adequately ap-
proximate the distribution of such data. the classical
application of RSM has provided satisfactory results.
Once a proper distributional form has been deter-
mined, the usual approach is to express the mean of
the distribution as a function of the experimental
conditions. Most often a second-order polynomial is
used. Mead and Pike (1975. p. 517). however, pro-
vided the algebraic form for a number of different
response functions that have been used. The distri-
butional form of the underlying data has an impact
on the estimation of the model parameters and on
the inferences drawn from an RSM analysis.
In the development of generalized linear models.
McCullagh and Nelder (1983) provided a framework
for handling such problems when the underyling dis-
tribution belongs to the exponential family. Thus this
approach is applicable. for example. when the bino-
 RESPONSE SURFkCE METHODOLOGY:
mial distribution is appropriate for describing quan-
tal data or when it is likely that the frequency of
recorded counts can be adequately described by the
Poissonmassfunction. Survival data also can be made
to yield to analysis through use of generalized linear
model methodology. The use of this approach to data
analysis is facilitated by the availability of well-doc-
umented software (see Payne 1985). Any potential
user of RSM in the biological sciencesshould inves-
tigate this work.
When modeling count data or quanta1 data, it is
sometimes the casethat there is more variability than
can be explained by the Poisson or binomial distri-
butions? respectively. In these situations use of more
general forms of these distributions-for example.
the negative binomial and the beta-binomial-has
been proposed. Solana. Chinchilli, Wilson, Carter:
and Carchman (1986) used negative binomial regres-
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sion in an RSM effort to model the relationship be-
tween the mean number of sister chromatid ex-
changesinduced per cell as a polynomial function of
the concentrations of the ethylnitrosourea and cis-
diaminedichloroplatinum.
4. SUBJECT-MATTER APPLICATIONS
In the two previous RSM reviews, much attention
was given to subject-matter applications. In the Hill
and Hunter (1966) review, chemical and processing
applications were illustrated, with real-life examples
demonstrating canonical analysis and use of multiple
responses.An example in which a canonical analysis
provided some insight (elucidation) into the mech-
anism in question was also given. The Mead and Pike
(1975) review produced examples in the biological
area. From our search. it is clear that standard use
of RSM has accelerated. In this section. we separate
applications that were reported in subject-matter
journals from applications that are finding use in in-
dustry. As expected, many imaginative applications
were found in the chemical and processing areas, but
we were somewhat surprised to find that uses have
spreadrather dramatically into other areas.We choose
to highlight a number of applications here. In this
survey of the subject-matter literature, several in-
teresting facts become apparent.
1. The central composite is used more than any
other family of RSM designs.
2. Although the methods of exploring the re-
sponse surface have become somewhat more so-
phisticated, users, nevertheless, are not close to mak-
ing maximal use of the enormous wealth of analytic
tools that are available. This is caused, in large part.
by the “lag time” that naturally exists between the
time at which a publication appears in the statistics
literature and the point at which it is adopted by
1966-1988 147
subject-matter users. As in the case of many areas
of statistics, however, our communication with the
user remains woefully inadequate. Perhaps the
quickest medium of communication is through effec-
tive computer software, but in the area of RSM,
there has been little planning and leadership in this
area of development. although recently there have
been some rays of hope that are discussed in Sec-
tion 5.
3. Nearly all practical RSM problems are truly
mdtiple response in nature. Sophisticated ways of
solving multiple-response problems are not generally
well known, however.
4.1 Applications in Physical and
Engineering Sciences
In the late 197Os,scientists dealing in the important
area of gas chromatography began using RSM meth-
ods. Scott (1970), Swingle and Rogers (1972), Kam-
bara, Hata, and Ohzeki (1968), and Turina, Trbo-
jevic, and Kastelam-Macan (1974) used variations of
RSM to determine optimum conditions for gas
chromatography. Morgan and Jacques (197X) stud-
ied relationships between flow rate, temperature,
stationary phase loading, and the responses.level of
separation. and analysis time. They indicated how
helpful an understanding of the system can be in
elucidating the nature of the response surface.
Person (1978) used RSM notions to analyze con-
tainment leakage from a sodium fire. “Sensitivity
studies” were conducted in which a study was made
of the influence of sodium mass. containment vol-
ume, radiation-heat-transfer coefficient, and sodium
oxide fraction-on-fraction leakage. Prato and Morris
(1984) studied the effect of detergent concentration,
agitation time, and washing time on the amount of
soil removed from fabric. To underscore the natural
application of RSM and second-order composite de-
signs in human-factors engineering-type experi-
ments, Simon (1970) illustrated with a study involv-
ing three display-panel-type variables and their effect
on target recognition for airline pilots.
Olivi (1980) discussedthe need for use of RSM in
exploring and identifying certain features of systems.
He uses as a *‘typical” application a study involving
five design variables with an orthogonal CCD. The
application involves factors that influence ballooning
time, an important variable in nuclear safety.
Bodden and Edwards (1982) used a Box-Behnken
design in an RSM study in the investigation of the
mechanism involved in the assay of cretinine. Clay-
comb and Sullivan (1976) used a three-factor CCD
and a ridge analysis of the data to illustrate the meth-
odology for selecting a cutting tool for maximization
of profit.
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 148 RAYMOND H. MYERS, ANDRE I. KHURI,
Contour plots of constant responsewithout an un-
alytic method for finding optimum conditions are often
the source of conclusions drawn by RShl analysts.
Such was the case in the work by Bretaudierc ct al.
(19SO)in a study of the analine aminotransferase
kinetic assay. Fujiwara, Hnraguch. and Fuwa (1975)
studied the atomization mechanism in air-acetylene
flames using response contours. Burtis, Bostick,
Overton. and Myocheck (1981) used data from CCD
to produce useful contours of constant response and
a canonical analysis that allowed for optimization of
a kinetic method that applies to the enzymatic mea-
surement of ethanol. Response contours were also
the subject of information obtained from a response
surface analysis in which interest centers on formu-
lation and optimization of vitreous bonds in an article
by Chait and Foltz (1981). The field of nucler engi-
neering has not been without studies involving RSM.
particularly when simulation is involved. Heller.
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Oelkers. and Farnswor (1977) used data from CCD
to study the mechanism involved in thermal-hy-
draulic margin analysis.
4.2 Applications in Food Science
The food industry has been a prime user of RSM
since the early 1970s. This is reflected in a study of
content of journal articles and in industrial usage as
well. We cannot begin to cite all of the work in this
area. Johnson and Zabik (1981) used a mixture de-
sign to build a response surface to study interactions
among proteins in angel food cake. Lah, Cheryan,
and Devor (1980) used a 2:-’ factorial with an im-
pressive application of steepest ascent to optimize
whipping properties of an ultrafiltered soy product.
R. G. Henika began using RSM at Foremost Foods
in the early 1970s. His leadership resulted in usage
by others. even though many of the applications in
this field involve rather precarious or tricky panel
data from sensory evaluations. The articles by Hen-
ika and Palmer (1976) and Henika (1982) are cer-
tainly important contributions. In the latter, he paid
particular attention to applications with sensory data.
Second-order models were used to find the nature
of the system relating gelling properties of a nzent
loaf analog to pH, salt content, cooking time. soil
isolate. and egg white level. Although formal optimi-
zation procedures were not used, the response sur-
face allowed Jao, Larkin, Chen. and Goldstein (1982)
to gain a better understanding of the mechanism.
Desirable gelling properties can be obtained with
reduced egg vvhite usage with proper manipulation
of salt content and cooking time.
The extrusion of starch has important applications
in food and industrial applicatons. El-Dash. Gon-
zales, and Ciol(l983) used responsesurface methods
TECHNOMETRICS, MAY 1989, VOL. 31, NO, 2
AND WALTER H. CARTER, JR.
to find ideal operating conditions in this area of tech-
nology. They discovered that. depending on the ap-
phcation. one can control levels of extrusion tem-
perature, screw speed. and moisture content to
produce the proper level of gelatination.
Daley. Deng. and Cornell (1978) used RSM to de-
termine the optimal combination of soy, sodium tri-
polyphosphate, and water to produce the most ac-
ceptable sausage-type product from minced mullet.
A CCD was used to study the effects of calcium chlo-
ride and cysteine on heat-induced whey-protein gel-
atin by Schmidt, Illingworth. Deng, and Cornell
(1979). After the parameters of a second-order poly-
nomial were estimated, plots of the fitted surface
were generated. Sefa-Dedeh and Stanley (1979)made
use of a CCD to fit the percent of nitrogen extracted
from a type of meal as a complete quadratic in time
of extraction, temperature of extraction. and meal-
to-solvent ratio. The fitted polynomial was explored
to estimate the levels of the independent variables
associated with optimal extraction of protein nitro-
gen. Mixture responsesurface methodology was used
by Huor, Ahmed, Rao, and Cornell (1980) in con-
junction with laboratory sensorv evaluation and
small-scale consumer tests to optimize the propor-
tions of watermelon, pineapple, and orange juice in
a fruit punch. Min and Thomas (1980) used RSM
analytic techniques to determine the relationship be-
tween ingredients and physical characteristicsof dairy
whipped topping and optimize the ingredient con-
centration by the simultaneous analysis of fat. corn-
syrup solids, and stabilizer to produce a dairy whipped
topping that could be frozen for storage and distri-
bution without adverseaffects.Lee and Hoseney(1987)
used RShqto optimize the formulation of single-stage
cake mixes for white layer cakes. RSM techniques
were used by Tseo, Deng. Cornell. Khuri. and Smith
(1983) to determine the optimum combination of lev-
els of washing temperature, washing ratio of water
volume to sample weight. and washing time on the
quality of minced mullet flesh. Tong, Jordan. and
Houghton (1984) used CCD to study the effects of
safflower-oil concentration, emulsifier concentration.
and freezing temperature on maximum overrun and
fat destabilization of ice cream. McLellan, Bernard,
and Queale (1984) used a rotatable experimental de-
sign to generate data for a sensory analysis of car-
bonatedcapple juice as a function of levels of car-
bonation and soluble solids. The fitted surface for
acceptability was described as having a ridge of high
acceptability runnin g through the range of typical
soluble solids and carbonation levels.
4.3 Applications in Social Sciences
Much use has been made of RSM in certain areas
in social sciences. Economics. operations research.
 :.
: RESPONSE SURFACE
and system simulation are but a few fields that have
benefited. Shechter and Heady (1970) used response
surfacetechniques to design and analyze experiments
from a simulation model dealing with the feed-grain
program. Four responses-net farm revenue, net farm
,evenue participants. stock accumulation, and go\-
ernment costs-were considered. Multiple response
analysis was discussed. In this case, the analysis al-
lows for an optimum decision rule regarding trade-
offs between increasing farm income and reducing
government costs. Montgomery and Bettencourt
(1977) produced an excellent account in which the
advantages of RSM methods in simulation studies
were reviewed. They put heavy emphasis on use in
multiple responsestudies. An interesting illustration
was given in which a simulation of a military tank
duel is analyzed to ascertain the values of two design
v-ariables(mean time to fire first round and mean
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time between rounds) that give desirable values of
four responses.They used a nonlinear programming
technique to analyze data taken from a rotatable
CCD.
Montgomery and Evans (1975) discussed the use
of various classes of second-order response surface
designsin simulation work. Two variable equiradial
designs,uniform precision rotatable CCD’s, and other
designswere discussed. They gave an illustration in
which a simulation of a six-intersection street-net-
w,ork system was used. Data was taken using a ro-
tatable CCD with two design variables. Canonical
ana!ysisrevealed a maximum at the stationary point.
The results produced optimum conditions on the se-
lection of traffic-signal settings.
Smith (1975) made an empirical study of various
optimum seeking procedures that are frequently used
in computer-simulation situations. The methods
studied were random search. one-factor-at-a-time
movement, RSM Version I. and RSM Version 11.
Version I involves use of two-level first-order designs
and the method of steepest ascent. and Version II
involves steepest ascent with the use of the simplex
design. RSM Version I appeared to give the best
result. Biles (1981) described a two-phase procedure
in which a complex search procedure is employed.
followed by a second-order analysis of the resulting
data. He gave an illustration of the method from an
inventory sy5tem.
4.4 Applications in the Biological and
Clinical Sciences
The techniques that constitute a response surface
analysis are being used more and more often in the
biological sciences. This is evidenced by the large
number of citations in the references of this article.
In this section, some of the more novel applications
wi!l be highlighted.
METHODOLOGY: 1966-1988 149
RSM techniques have been found useful in the
study of the relationship between the chemical struc-
ture of a compound and its biological activity. Mager
(1983a, 19s3j studied the structure-neurotoxicity re-
lationship of organophosphorous pesticides in this
manner and used a canonical analysis of the fitted
equation to elucidate properties of the responsesur-
face. hlager (19S2b) also studied the activity of ri-
famycin derivatives against a rifamycin-MS-resistant
mutant of Staphylococcus aureus.
Several references in the microbiologic literature
(Cinto, Galvagno. Forghiassin, and Ranalli 1977:
Farrand, Linton, Stephenson. and McCarthy 1983:
Maddox and Richert 1977) indicated the useful ap-
plication of RSM techniques, including the use of
rotatable CCD’s to optimize microbiological media
for the growth of various microorganisms. Cheynier.
Feinberg, Chararas. and Ducauze (i9S3) demon-
strated that a yeast isolated from the digestive tube
of the larva of a parasite of eucalyptus trees was
cap;,ble of bioconverting citronella1 to citronellol.
RSh4 procedures were used to achieve the optimi-
zation of the experimental conditions for that bio-
conversion process.
Various industrial-pollution studies have em-
ployed response surface methodology. Huck, Mur-
phy, Reed, and Leclair.(T977) determined the poly-
mer properties and mixing conditions required to
produce optimal flocculation for mine waters of spec-
ified strengthscontaining iron, zinc, and copper either
singly or in combination. Wallis (197s) reported on
the use of RSM in studies related directly to power-
station cooling systems.
Dincer and Ozdurmus (1977) used the method of
steepestdescent to determine the most suitable com-
bination of four independent formulation and pro-
cess variables for the disintegration time of coated
tablets in simulated intestinal fluid. Shek. Ghani. and
Jones (1980) evaluated the potential of the Nelder-
Mead simplex searchprocedure for optimizing a cap-
sule formulation. At the completion of the search,
these investigators fitted a polynomial model to the
data and plotted the estimated response surface. In
a similar study, Chowhan, Yang. Amara. and Chi
(19S7) studied the effects of moisture and crushing
strength on tablet friability and in vitro dissolution.
They used a complete second-order model in the
independent variables to graduate the responsesur-
face. The fitted model was explored by plotting con-
tours of constant response and estimating the loca-
tion of the stationary point. Fast, Sampson.Whitner.
and Ali (1983) used CCD with five independent vari-
ables in an assayfor creatine kinase. A simplex max-
imization algorithm was used to determine areas of
maximum sensitivity. Belloto et al. (1985) used RSM
to study the solubility of pharmaceutical formula-
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 150 RAYMOND H. MYERS, ANDRt I. KHURI,
tions. They also discussed the optimization of one
response in the presence of constraints due to the
consideration of other response variabies.
There are numerous reports in the clinical-chem-
istry literature on the use of response surface meth-
ods. Rautela, Snee, and Miller (1979) described an
approach that permitted the determination of accu-
rate optima required for the formulation of annlyt-
ically reliable clinical methods. Thompson, Hodges.
Dobler, and Williamson (1981) reported on the use
of simultaneous RSM optimization techniques to op-
timize an assay for alkaline phosphatase. London,
Shaw, Theodorsen, and Stromme (1952) used RShI
to optimize the assayof gamma-glutamyltransferase.
They noted that, although such techniques do not
yield a mechanistic understanding of an enzyme as-
say. they do produce an operational understanding
of how an assayfunctions. In a similar article, Cole-
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man, Perry> and Wehrly (1983) used RSM to opti-
mize assaysfor antithrombin III and plasminogen.
Roush, Petersen, and Arscott (1979) discussedthe
usefulness of an RSM approach in poultry-nutrition
research. Body weight and feed-conversion response
for Japanese quail were optimized as functions of
protein and energy levels. Roush (1953) used a cen-
tral composite experimental design with male broil-
ers to examine quantitatively the protein levels in
starter and finisher rations and the time of ration
changeto optimize body weight, carcassweight, feed
conversion, and net profit.
RSM’s have been used to elucidate the actions and
interactions of cytotoxic drugs in combination and to
estimate the optimal levels of each drug for the treat-
ment of cancer with and without side-effect con-
straints. Carter, Wampler. and Stablein (1953) dis-
cussed the use of logistic and proportional hazards
regression models to this end. They gave software
for the estimation of the stationary point and con-
fidence regions around its location obtained from the
use of these models. The history of the use of RSM
in cancer research was reviewed by Carter and
Wampler (1986). Although the examples used in-
volve data from animal studies. there is interest in
applying these techniques to clinical studies. Cur-
rently the Mid Atlantic Oncology Program, a re-
gional multi-institutional cooperative group. is run-
ning a clinical trial in the study of breast cancer that
is designed as a factorial experiment and will be ana-
lyzed using responsesurface techniques. (For details.
contact the Mid Atlantic Oncology Program Office,
3500 Reservoir Road, N.W., Washington, DC.)
4.5 Industrial Use of RSM
The 19SOsbrought a new urgency in industry in
the United States. an urgency that underscores the
need for quality. As we indicated in Section 3. there
TECHNGMETRICS, MAY 1989, VOL. 31, NO. 2
AND WALTER H. CARTER, JR.
is a new motivation in American history brought about
by the successenjoyed in Japan in the use of quality
control and efficient statistical methods. The areas
of experimental design and, specifically. response
surface methods arc receiving considerably more at-
tention than before. This new and renewed interest
is “fallout” from this searchfor quality and precision,
In our communication with industrial statisticians
and research workers, we found use of RSM among
a wide variety of types of industrial companies. In
most casesthey sought and, of course. were promised
anonymity. Our search did reveal some interesting
but not unexpected information.
1. In addition to the central composite and Box-
Behnken designs,fractions of two-level factorials and
Plackett-Burman designs are used to a large extent,
with the simplex design used in conjunction with di-
rect optimization. There is also a growing usage of
computer-generated RSIM designs.
2. In regard to RSM analysis, some analysts carry
the computations through to an optimization phase,
but others do not. Ridge analysis is used for finding
candidates for optimum operating conditions. ai-
though usageis not as extensive as one might expect.
Some users merely use graphical methods with over-
laid contour plots.
There is no universal software tool for doing RSM
analysis. In particular, some users use International
Mathematical and Statistical Libraries (IMSL) sub-
routines, and some resort to in-house software ver-
sions for finding optimum conditions. Some users in
industry appear frustrated by the lack of software for
finding optimum conditions and resort to two-di-
mensional contours for analysis.
In what follows, a sample is given of RSM sce-
narios that apply to actual RSM users in industry.
We have attempted here to give samplesacrossmany
fields of application.
A tobacco company uses RSM as a primary tool
for elucidating fundamental relationships and search-
ing for optimum conditions in the caseof nearly every
new product considered in a research effort. They
use no software for design construction, but they use
in-house software developed from numerical-analy-
sis algorithms for analysis. The latter allows for op-
timization under various types of constraints on the
design variables. The designsused vary considerably.
For problems in which cost is important. Plackett-
Burman screening designs are used and hybrid and
small composite designs are usedin the second-order
case. Central composite and Box-Behnken designs
are used extensively. Problems are almost always
multiple response in nature. although the responses
are too many in number to often do formal multiple
response optimization.
 RESPONSE SURFACE METHODOLOGY:
A large oil company uses RSM to a moderate ex-
tent. Applications vary from polymer optimization
to the exploration of a detergent system. In some
applications the design variables are of the ~z151~~w
type. Mixture \-ariables and process variables often
occur in the same setting. The computer program
ACED (see Welch 1985) is often used to generate
the design in the mixture situation. Basic two-level
factorials and CCD’s are also used. In some cases,
determination of optimum conditions is important.
The algorithms in GRG2 (see Cornell 1981) and
NSTAT (1984) are generally used to find optimum
conditions. This company also envisions considering
RSM in the future for plant-scale problems dealing
in perhaps more than 1.000variables-that is, allow-
ing the technique to play a role in control theory.
A chemical company finds that RSM design and
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analys,iscan be used to solve two types of problems.
The first is a region-seeking procedure in which one
is seelking the general vicinity of “best” operating
conditions. The method of evolutionary operation
descrilbedby Box (1957) is often used. Some success
has been experienced with the Spendley, Hext, and
Himsworth (1963j simplex algorithm. A computer
program has been developed that makes use of var-
ious types of designs and allows input of experimen-
tal results and calculation of the next experimental
run. It has been found that the most difficult aspect
of this procedure is obtaining from the experimenter
a commitment on combining response values from
the multiple dependent variables so that the simplex
will move. In the second problem encountered b!
the chemical company, they are near the optimum
and wish to locate or confirm its exact location. CCD’s
are used to a large extent. Small composite designs
are often used with no concern for either orthogo-
nalitp or rotatability.
A large food company has used RSM in several
studies. It is usedin product development and in cost-
reducing old products. The responsesare either con-
tinuous variables or consumer acceptability ratings.
RSM is also used in process control and in the e\,al-
uation of ne\v equipment. Generally. for first-order
models, two-level factorial or Plackett-Burman de-
signs are used. In the case of second-order models,
Box-Behnken designsand CCD’s are used. At times,
the CCD is resisted by the experimenter, because
five levels become inconvenient due to difficulty in
adjusting equipment accordingly. Errors in control-
ling factor levels occur quite often.
Another large and Lvcll-diversified chemical com-
pang makes use of RSM on a research level. This
Companvhas a large group of professional statisti-
cians anh an in-depth program to teach basic esper-
imental design to engineers
L. and scientists. They make
“se of :an in-house computer procram that assists
i966-1988 151
nonstatisticians in designing and anal!,zing experi-
ments. The program involves contour plots and op-
timization routines. There is great potential for use
of RShl in this company. and most problems are
multiresponse in nature. Mixture problems are the
rule, and an algorithm has been programmed in-house
to generate mixture designs described by Thompson
and Myers (196s). Extreme-vertexesdesignsare used
as Lvell. In addition. considerable use is made of the
ACED (Welch 1955) algorithm for design construc-
tion.
A large research-and-development organization
makes use of RSM in several topical areas, including
chemical and fermentation optimization and devel-
opment of consumer food products. In addition, it
is also used for optimization of settings associated
with processesin the refining and hydrogenation of
vegetable oils. In almost all cases. “optimization”
requires arriving at the most agreeabie compromise
among various conflicting responses. In the case of
two design variables, the choice of best conditions is
found by use of graphical overlay contour plots. For
more than two variables. a utility function is con-
structed and a Nelder-Mead (1965) simplex opti-
mization routine is used to identify an acceptable
region in the design space. In some instances ridge
analysis is used to either find optimum conditions in
a single responsesituation or to find regions for sub-
sequent experimentation. The class of CCD’s is re-
lied on heavily. Blocking is often required. and CCD’s
that block orthogonally are used.
Researchers at a regulatory agency ha\,e used re-
sponsesurface techniques to evaluate the effect of a
combination of toxic substanceson the hatch rate of
fish embryos. Three-dimensional plot routines of the
fitted surface were used to gain insight into the re-
lationship.
A consulting firm used the results of an RSM study
to develop a generic method for evaluating subma-
rine-tracking algorithms. Simulation experiments
were conducted under common setsof scenarios, and
then algorithm performance was el,aluated according
to the behavior of the response surfaces generated.
RSM is also under consideration for se\~eralsonar-
operator studies to determine the effects on perfor-
mance of various processingschemes.Their analvses
were performed using IA4SL subroutines.
5. FUTURE DIRECTIONS OF RSM
To comment about future directions of RSM. one
must ponder the present status with regard to use
and importance. RSM is being used in industry more
and more, but the use does not reflect recent ad-
vances as much as one might \vish. The “fallout” of
the recent, almost passionate. push for quality and
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
 152 RAYMOND H. MYERS, ANDRE I. KHURI,
experimental design in industrv is bringing RSM to
the attention of many potential users. Usage lags far
behind its potential. however. Several factors may
have contributed to this, the most prominent of which
we believe are explained in the following paragraphs.
There is a severe lack of communication between
academic statisticians in this country and those in
industry. There are some attempts at communication
and few successes. This is true in many arcas. not
merely RSM. One testament to this is the fact that
Japanese statisticians give lectures and short courses
to industrial companies in this country on effective
use of experimental designs that are based, in large
part, on basic concepts developed in the United States
and the United Kingdom years ago. There is no ques-
tion that the historical underpinnings of RShI were
produced with particnlcrr rypliccztiom irz r?zitlti. When
we move away from research that does not have
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particular problem solving as motivation. wt lose our
line of communication. Statisticians in academia bear
much but not all of the burden. They have little
access to what is actually going on in industry as far
as the deployment (or lack of it) of RS&l is con-
cerned. This can be partly attributed to the fact that
“sometimes. those in industry are dissuaded from
publishing for fear of revealing proprietary infor-
mation” (Hahn 1983, p. 114). Even a search of the
literature. statistical or otherwise. in an effort to find
a real data set to use in an example can sometimes
be unwieldy.
There has been a severe software problem. It is
true that data analysts are attracted mostiy to statis-
tical techniques for which software has been bvritten.
Good. efficient, well-documented software is a swift
and sure form of communication. There are practi-
tioners who still believe RSM is “only regression”
and that they should use regression software not RSXl
software. Of course, there are many new packages
available for constructing experimental designs, and
RSM designs are the subjects of some of these pack-
ages. In the area of analysis, there are some recent
rays of hope. The potential user is referred to Nacht-
sheim (1957), who gave a comprehensive review of
the current situation with regard to computer-aided
design of experiments. He included a section on
available packages for ‘*Sequential Experimental
Optimization of Response Surfaces” and pointed out
that there are several packages with RShI analysis
capabilities. including optimization.
Steinberg and Hunter (1984). alon with the dis-
cussion that followed. expressed concern about the
aforementioned communication problems and of-
fered several remedies. Better cooperation and more
formal lines of communication between academia and
industry are needed. Statisticians, scientists. and en-
gineers can learn and benefit from one another. This
TECHNOMETRICS, MAY 1989, VOL. 31, NO. 2
AND WALTER H. CARTER, JR.
fact is certainly not specific to RSM but applies more
broadly to the discipline of statistics.
In what follows, we indicate what. in our opinion.
are proper directions for future research. but let us
emphasize that users are sufficiently far behind in the
use of RSM tools that the need for proper commu-
nication is far moI-e pressing. One of the revie\vers
of this article put it quite well when he indicated that
communication may merely involve formulating
problems objectively with subject-matter scientists.
and that, sadly. may res;ilt in our greatest contri-
bution.
Future Research Directions
Multiple responses. sequential designs and anal-
yses, and designs for the less orthodox RShI appli-
cations are some areas where one may benefit from
immediate research. Both design and analysis in-
volving multiple responses have received precious
little attention in spite of the acute need for them.
Biolo@sts. as well as engineers, are finding appli-
cations of RSXl in which the model is nonlinear-
for example. logistic and other standard growth
models. A fruitful area of research would be the
study of designs for certain specific nonlinear func-
tional forms.
We suggested in Section 3 that the RSM user needs
to learn from the Taguchi approach that system vari-
ability should be a major component in the analysis.
A similar argument can be made for consideration
of the distribution of \,ariance of prediction in as-
sessments of experimental desigs. Often the success
of the RSM endeavor is dependent on the properties
of j at different locations in the design space. hlnny
standard designs hal:e prediction variances which in-
crease dramatically as one gets close to the design
perimeter. As a result. any conclusions drawn (re-
garding choice of optima or improvements in oper-
ating conditions) concerning response near the de-
sign boundary are suspect. Yet we see very little that
deals with this in design assessment or comparisons
among designs. We too often evaluate a design on
the basis of one number (say. D-efficiency) Lvhen the
important aspects of behavior are multidimensional.
Much has been written. of course. about com-
puter-generated design. The comments on the Stein-
berg-Hunter review reflect the general opinion that
computer-generated designs present a very promis-
ing area for the future. This is certainlv true in regard
to the tield of RSM designs. The danger that is pro-
jected by concerned academicians is even more acute
in the RSM area. Many (though not all) methods of
generating experimental designs employ criteria that
do not address robustness notions such as model mis-
specification. anticipation of outliers. errors in con-
 RESPONSE SURFACE
trol. extrapolation. and so forth. All of this suggests
that preparing for the nonideal and the deployment
of very detailed interactil’e properties are high prior-
ities in computer-generated RSM design.
There appears to be some need for the develop-
ment of nonparametric techniques in RSM. Most of
our analytic procedures depend on a model. The use
of model-free techniques would avoid the assump-
tion of model adequacy or low-order polynomia! ap-
proximations and, in particular. the imposed sym-
metry associated with a second-degree polynomial.
The use of nonparametric kernel estimation shows
some promise.
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