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Development of the ORBIT model was a collaboration between multidisciplinary
academic researchers and program ofcers at the National Institutes of Health (NIH).
(See Appendix at the end of this chapter.) The rationale for this collaboration was
that issues in behavioral treatment development are fundamentally multidisciplinary,
requiring infrastructure support that is typically provided at the federal level.
Recognizing the importance of behavioral treatment development, the NIH Ofce of
Behavioral and Social Sciences Research (OBSSR), in collaboration with the
National Heart, Lung, and Blood Institute (NHLBI), the National Cancer Institute
(NCI), the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK),
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), and investigators from the U01 ORBIT consortium orga-
nized, in 2010, a cross-disciplinary conference of experts in elds related to the
development and early testing of behavioral treatments for chronic diseases. An
important goal of this conference was to propose guidelines for developing behav-
ioral treatments to prevent or manage chronic diseases. Areas of emphasis included
the identication of innovative approaches to solving important clinical problems
based on basic behavioral science theory and research, the design and preliminary
testing of promising treatments, and readiness to conduct a Phase III behavioral ef-
cacy trial. Conference participants included members of the ORBIT consortium,
NIH program ofcers, and experts in discoveries, designs, methodologies, and infra-
structures needed to develop and test innovative, health-related behavioral treatments
(Conference information can be found at http://www.nihorbit.org/ORBIT%20
Content/Workshops%20and%20Conferences.aspx?PageView=Shared).
Overview
Figure 3.1 presents the revised ORBIT model for behavioral treatment develop-
ment. It is a progressive approach characterized by purpose-guided phases. The
intent is to guide the collection of a chain of evidence needed to support the case
that a behavioral treatment could improve a chronic disease endpoint.
The purpose-guided phases are modeled after the widely-accepted phases of drug
development [6]. The Discovery phase encourages creative insights about signi-
cant questions, and strong treatments through multidisciplinary crosstalk among
medical clinicians, basic scientists, applied scientists, and theoreticians. The Design
phase is characterized by a focus on the dimensions of a treatment. It features a
uid, exploratory dene phase where tinkering (i.e., ddling or playing with a treat-
ment) during the course of systematic observation is at a premium, followed by a
rene phase where the goal is to maximize the efciency with which a treatment is
delivered without losing efcacy. The milestone for completion of the Design phase
is a xed treatment ready to begin efcacy testing accompanied by a quantied
pathway by which the treatment is hypothesized to translate into a chronic disease
outcome. The Preliminary Testing phase features progressive testing, moving from
small and inexpensive early tests to larger, more expensive, and conclusive later tests.
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Fig. 3.1 The revised ORBIT model for development of behavioral treatments for chronic diseases
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This model is progressive but not linear or proscriptive. A natural progression of
questions evolve from a focus on exploration, to dening the basic elements of treat-
ment, and then to evaluating the impact of treatment. This evolution of questions,
and a convenient time to answer them, is presented in Table3.3. But this is not neces-
sarily a linear process. Many treatments do not need answers to all of these questions
because much is already known about them. Nor does the model restrict the timing
for asking specic questions. For example, a treatment could be rened and opti-
mized before progressing to an efcacy trial or after a successful efcacy trial. The
former “building” approach maximizes efciency, economy, and scalability, while
the latter “dismantling” approach maximizes efcacy. Since both approaches are
sound, the ORBIT model leaves such timing decisions to the investigative team.
Table 3.3 Progressive questions of interest in the design and preliminary testing of a
behavioral treatment and a convenient time to answer them
Timing Questions
Exploratory
studies
Phase Ia
– What is the impact of a treatment, or potential treatment compo-
nents or strategies, on a variety of behavioral, biomedical, and/or
surrogate endpoints?
Renement studies
Phase Ib
– Can a treatment be optimized for efciency, without losing
efcacy, by modifying elements such as number of components,
mode of administration, duration, or intensity?
– Is treatment effectiveness moderated by diverse subgroups?
– Does a treatment or component affect hypothesized behavioral
and/or biomedical mechanisms?
– Can a treatment or component be implemented with delity?.
Proof-of-concept
studies
Phase IIa
– Is it plausible that a treatment can produce a clinically signicant
benet on a behavioral risk factor?
– Is it plausible that a treatment can produce a clinically signicant
benet on a chronic disease or surrogate endpoint?.
Feasibility and Pilot
studies
Phase IIb
– Can a treatment and/or trial protocol be implemented with delity
in different settings or at different collaborating sites?
Phase II efcacy
trials
Phase IIc
– Does a treatment produce a clinically signicant benet on a
behavioral risk factor?
– Does a treatment improve a behavioral risk factor better than
chance alone, non-specic attention, passage of time, and/or
current behavioral or biomedical treatments?
– Does a treatment improve a relevant biomedical risk factor or
surrogate endpoint?.
Phase III efcacy
trials
Phase III
– Does a treatment produce a clinically signicant benet on a
chronic disease endpoint?
– Does a treatment work better than a clinically important compara-
tor such as the standard of care, an enhanced standard of care, a
placebo, or no treatment?
Effectiveness trials
Phase IV
– Can a treatment be implemented with efcacy and delity in
diverse clinic or community settings?.
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This model encourages continuous renement and the freedom to fail. The bidirec-
tional arrows between all phases are intended to expand investigator options, in light of
results, from only “progress” or “abandon” to include the third option of “rene.” In
many cases, renement in the face of failure is the seedbed for innovation rather than a
cause for abandonment. Regardless of the stage of development, each new study pro-
vides an opportunity to rene. The existence of a hypothesized pathway shows where
in the pathway goals might not have been met and renement might be needed.
The ORBIT model has been rened to include Phase II efcacy trials among the
activities of Preliminary Testing (Fig. 3.1). In the previous version of this model
[15], Phase II efcacy trials were subsumed under the category of Phase III efcacy
trials. This revision distinguishes Phase II trials, those with behavioral, biomedical,
or surrogate outcomes, from Phase III trials which have a chronic disease outcome.
This is an important and intentional distinction. The majority of trials that have been
conducted on behavioral treatments are Phase II trials, but the standard of evidence
that is required to incorporate a treatment into clinical practice is Phase III trials. It
is hoped that this distinction will provide a rationale for encouraging progression to
Phase III trials.
Details of the questions and methods that are characteristic of each of the purpose-
guided phases follow and serve as an extension and elaboration of the original pre-
sentation of the ORBIT model [15].
Discovery
At its earliest stages, behavioral
treatment development begins
with the discovery that a behav-
ioral strategy might solve an
important clinical problem.
Unexpected creative insights and
recognition of potential are right-
brain processes. This is different
from the left-brain mindset of
attention, focus, concentration,
and linear development within
which most academics live.
Discovery is propelled by the drive
for exploration, the thrill of the
chase, and an openness to experi-
ence. In Proust’s words,
“The real voyage of discovery is not in traveling to new lands, but in seeing old lands with
new eyes.”
Creative Discovery and
the Birth of Behavioral Medicine
Meyer Friedman, a respected San
Francisco cardiologist practicing in the
1960s, noticed that the fabric on the seats
of the chairs in his waiting room was worn
out only at the front. Why? After ponder-
ing this for some time, he made the cre-
ative leap that this was a sign of time
urgency. The patients were literally dget-
ing on the edge of their seats when having
to wait for the doctor. This gave birth to the
hypothesis that coronary disease was
caused, in part, by stress, one component
of which was time urgency. This discovery,
called Type A behavior, marked the begin-
ning of the eld of behavioral medicine.
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Discovery is a non-
linear, disorga-
nized, and chaotic
process with unex-
pected twists and
turns in thinking. It
is precipitated by
the discomfort of a
prolonged impasse
in left-brain activ-
ity. A change in
activity can activate
the murky but in-
nite library of asso-
ciations in the brain
where the magic of
right-brain pro-
cesses happen [29].
Insight comes as an
unexpected epiph-
any, in the shower
or during a walk,
with a remarkable
degree of con-
dence in the right-
ness of the solution.
This moment of
sudden insight “just
seems obvi-
ous” [30].
Most academic environments inhibit these creative connections by placing more
value on product than process. But for those inclined toward process, discovery of
innovative ideas is a skill that can be nurtured [32]. It is an essential part of the earli-
est stages of behavioral intervention development. It is essential to the creative con-
nection between a signicant clinical problem and the possibility that it could be
solved with a behavioral treatment. It is essential to the creative connection between
a principle of human behavior and the application of that principle in the service of
enhancing the focus, strength, and sophistication of a behavioral treatment.
Discovery ofaSignicant Clinical Problem
The ORBIT model encourages a close connection between applied behavioral sci-
entists and clinicians in medical practice. Face-to-face connection is better than
simply reading the medical literature. The unpredictable and uncontrollable creative
process needs to be stimulated. Becoming a participant observer within a clinical
context makes it possible to see the world through the eyes of a clinician and of a
patient. Discovery may include the following.
What Sparks Creativity in Entrepreneurs [31]
“A 3-mile walk. My head de-clutters and I think clearly.”
“Preparing food. I get lost in the process. My brain rests
and I have my best ideas.”
“Reading in bed before sleep. I oat into another world and
my imagination ows.”
“Diving in the ocean. No phone, no internet, no talking, no
noise. Just the sound of my breathing and the calming lull of
the ocean.”
“Walking my dog. I credit him with some of my best ideas.”
“Driving.”
“When I am on the move, usually in the air at 30,000 feet. I
consider conversations I have just had and the brand new
perspectives they invite.”
“Mowing the grass with a push mower. The combination of
the outdoors, strength, cardio, and repetitive motion frees
my mind.”
“When my head is buried in data and I am exercising my
brain. Sometimes something that was lying dormant inside
pops out. May be unrelated… it’s very funny.”
“A quiet milkshake shop with a comic book. The carb boost
and the creative reading give me positive energy and
motivation.”
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• The rst step in the clinical algorithms for management of blood pressure,
lipids, and prediabetes is lifestyle change [33–36]. But providers often go
right to the second step—drug management—because neither they, nor
their patients, have much faith in, or access to, lifestyle change programs.
• Regardless of the nature of the disease, patient adherence to prescribed
drug therapy hovers around only 50% [37, 38]. Provider adherence to
evidence-based guidelines for drug therapy is not much better [39].
• Orthopedic surgeons are becoming interested in obesity management.
Even though it is a major risk factor for hip or knee replacements, their
interest is based upon the fact that obesity undercuts both peri- and postop-
erative surgical outcomes.
• Many neurosurgeons would welcome an effective pre-surgical smoking
cessation program since smoking is associated with worse outcomes fol-
lowing neurosurgery.
Table 3.4 presents a
way to identify a sig-
nicant clinical prob-
lem. A disease may be
important because of
the breadth of its
impact, its cost, and/or
its unfavorable trends
over time. There may
be no current treatment
for this disease. The
current treatment may
not be potent or durable
enough to change an
important clinical out-
come. The current
treatment may be
effective, but adherence
to it is poor, it has too
many side effects, or is too costly for routine use. These problems could be solved
by the new treatment. It targets a novel pathway or a novel risk factor. It is less
costly and/or has fewer side effects than the current treatment.
Early identication of a signicant clinical problem provides an ultimate goal for a
program of research. Framing the problem from a medical perspective encourages
early focus on several important priorities.
• It sets sights on a Phase III efcacy trial to provide a conclusive test of whether
or not a behavioral treatment can solve an important medical problem.
• It encourages consideration early in the developmental process of what a
clinically meaningful medical outcome would be.
Table 3.4 The argument for a signicant clinical problem
Disease • Affects many
• Affects a subgroup
• Is increasing
• Is increasing in a subgroup
• Is not decreasing
• Is costly
Current
treatment
•
No current treatment
• Not very effective
• Uncertain effectiveness (clinical equipoise)
• Effective but adherence is poor
• Effective but side effects are serious
New treatment • Shows promise in preliminary work
• Targets novel risk factor
• Targets novel pathway
• Less costly than standard
• Fewer side effects
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• It makes it possible to judge success of intermediate steps in treatment
development on the ability of the behavioral treatment to improve surro-
gate markers of the clinically meaningful medical outcome.
• It encourages commitment to achieving a clinically signicant level of behav-
ioral change from the treatment that is potent enough to produce meaningful
change on the clinically meaningful medical outcome.
Discovery ofaBasic Science Basis for Treatment
A Phase III behavioral efcacy trial is based upon the assumption that change in a
behavioral risk factor following an intervention will be potent enough to produce a
clinically signicant improvement on a chronic disease endpoint. The ORBIT
model encourages close connections between basic and applied behavioral and
social science to maximize the potency of the intervention. Traditionally, theory has
formed the foundation of applied behavioral treatments. A number of theories of
behavioral change exist, but they are often nonoverlapping, imprecise, not coherent
with one another, not falsiable, and not widely accepted within or across disci-
plines [40, 41]. Basic experimental studies, upon which theory is often based, iden-
tify specic mechanisms that drive behavior and thereby provide a more precise
basis for choosing components and techniques that inuence these mechanisms.
Research aimed at identifying mechanisms of initiation, personalization, and main-
tenance of behavior change is the foundation of the NIH Science of Behavior
Change (SOBC) Common Fund program [42].
Following are some examples of how the basic science of fundamental human pro-
cesses can maximize the strength, integrity, sophistication, innovation, and promise
of behavioral treatments.
• Neuroscience experiments show that mobilization of executive function
can serve as a “brake” on impulsive eating [43]. This could form the basis
of an intervention aimed at reducing impulsive eating by enhancing execu-
tive function with self-management skill training in such areas as planning
and problem-solving.
• Neuroscience studies of the area of the brain engaged while making food
choices have shown that patients with anorexia nervosa who choose low-
calorie foods engage the dorsal striatum, the center for automatic behavior.
Thus, rather than previous explanations for anorexia which focus on
single- minded self-control [44], it may be rmly entrenched automatic
habits that override primary hunger drives [45, 46]. A novel treatment for
eating disorders would cultivate the development of new, automatic habits
[47], using the principles of habit formation [48].
• Behavioral economics experiments show that people disproportionately
respond to immediate rather than distal incentives [49]. Thus, motivation to
engage in physical activity may be strengthened by the rationale to improve
mood, rather than the rationale to lose weight or prevent a heart attack.
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• Basic studies of infant cognitive development have identied six aspects
of the environment that foster accelerated learning [50]. But the learning
environments of older adults are often decient in these six environmental
factors. An intervention for older adults that creates an optimized learning
environment featuring these six characteristics could be an innovative
way to enhance learning, improve brain health, and challenge the belief
that “You can’t teach old dogs new tricks” [50].
• The DARE (Drug Abuse Resistance Education) program to prevent drug
abuse in teens by having police lecture to kids in elementary school was
the cornerstone of prevention between 1980 and 2009, offered in 75% of
American schools, and cost taxpayers between $200 million and $2 bil-
lion. A series of meta- analyses evaluating both short- and long-term effects
showed no benet on drug abuse and the possibility of a “boomerang”
effect of encouraging drug abuse in teens [51, 52]. Prevention scientists
revised the program using a translational research model that drew on the
basic science principle of interactive “learning by doing.” This revision
resulted in dramatic reductions in substance use, replaced the original
DARE curriculum, and is now offered throughout the United States and in
44 other countries [53].
In summary, the key feature of the Discovery phase is crosstalk among practitioners
in clinical medicine, basic behavioral and social scientists, and applied behavioral
scientists. While a clinical problem can foster a search for relevant basic science
guidance, basic science discoveries can inspire an application of those insights to
the solution of a pressing clinical problem. Several relevant but independent basic
science ndings can justify a multi-component treatment, each component of which
has its own treatment target and methods of accomplishing change. If early testing
shows that a treatment approaches, but does not achieve, clinically signicant mile-
stones, avenues for optimization may be informed by going back to basic science
insights.
The Design Phase: Phase I
The overall goals of the Design phase are to assemble and rene the basic features
of a behavioral treatment. Subjects can be a small number of highly selected indi-
viduals who are studied intensively, rather than a more representative group.
Protocols can be uid, rather than xed, permitting ongoing adjustments while in
the course of observing, in response to evolving ndings. Tinkering with a treat-
ment to try to boost its strength, even when in the middle of systematic observa-
tion, is encouraged. Failures present opportunities to rene, at minimal cost, rather
than to abandon treatments. Milestones for judging success are based upon
achievement of pre-specied, clinically signicant goals which are deliberately set
to be ambitious in early studies to provide a needed cushion for subsequent testing
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in more diverse samples. This
phase is divided into two parts:
dening the basic elements of
the treatment and rening it to
improve efciency without
reducing strength.
Dene theBasic
Elements: Phase Ia
Purpose.
One of Steven
Covey’s 7 Habits of Highly
Effective People [54] is “Begin
With the End In Mind.” To illus-
trate this habit, consider under-
taking a road trip from
Washington DC to San
Francisco. The “end” is San
Francisco. To get to it, the trip
would most likely be guided by
a GPS or some other type of
roadmap. Without a map, fol-
lowing the sun would achieve
eventual success, but a roadmap would be more efcient. The implication for behav-
ioral treatment development is to dene the “end,” and the roadmap for arriving at it,
early in the developmental process to promote direction and efciency. This roadmap is
the hypothesized pathway. It is the essential product of the Dene phase. Table3.5 sum-
marizes the goal, common questions, selected methods, and milestone for progression
that characterize this phase.
Common Questions and Selected Methods. Some of the common ques-
tions of concern in the early Dene phase of treatment development follow.
Question: What is the
ultimate clinical endpoint
and how much improve-
ment on it would be clini-
cally relevant? If the goal
is to push toward a Phase
III efcacy trial, the ulti-
mate endpoint will likely
be a disease. Rena Wing,
the architect of the suc-
cessful and now famous
Diabetes Prevention Program [55, 56], was faced with this question early in her career.
She showed this photo in her presentation, Development of a Behavioral Clinical Trial:
Tinkering
DefinitionAttempt to repair or improve
something in a casual or desultory
way, often to no useful effect
UsageThey tinkered endlessly with the car
Synonymsadjust, fix, mind, play with, fiddle
with mess with, trifle with, dabble,
muck about, take apart
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The Road from Discovery to Action, at the NIH-sponsored ORBIT Workshop on
Treatment Development: From Ideas to Interventions. After pursuing a career studying
weight loss interventions, she was told by her advisors “You need a disease.” This would
both maximize impact on medical care and enhance funding potential within the dis-
ease-specic NIH Institutes. Because of the strong connection between obesity and dia-
betes, she chose diabetes. This is when she jumped from one rock (weight loss studies)
to the other (weight loss for diabetes management). Her investigations shifted from
studying strategies for weight loss to studying the implications of weight loss on diabetes
and its biomarkers.
Specifying a disease of interest, developing sophistication on why it is a problem,
and understanding the current state of the art in managing it provide the context
within which a new behavioral treatment will be offered. Could the new behavioral
treatment be better than existing treatments? Could it do as well as existing treat-
ments but at less cost? Clinically relevant milestones for success in improving a
disease endpoint can be identied by referencing the success rate achieved by cur-
rent state-of-the-art treatments. (See Chapter 5: Clinical Signicance.)
Table 3.5 Dene the basic elements (Phase Ia)
Central Goal Common Questions Selected Methods Milestone
A priori
specication of
the structure
and goals of
treatment
What is the ultimate
clinical endpoint and how
much improvement in it
would be clinically
relevant?
What is the behavioral risk
factor target that could
improve the clinical
endpoint and what level of
improvement in it is needed
to move that clinical
endpoint?
What are promising
components, and strategies
for change in them, that
could improve this
behavioral risk factor?
What level of
implementation of these
strategies is needed to
achieve clinically
signicant improvement in
the behavioral risk factor?
Clinical guidelines
Meta-analyses
Advice from clinicians
Epidemiologic studies
Meta-analyses
Experiments
Cross-sectional studies
of covariation between
a behavior risk factor
and a surrogate disease
endpoint
Basic behavioral/social
science studies
Theory
Experiments
Ecologic studies
[
57–59]
Small N studies [
60–65]
A quantied,
hypothesized
pathway by which a
behavioral treatment
could solve a
pressing clinical
problem
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