CHAPTER

C o n t rolled Clinical Trials Versus Case

S t u d i e s : W hy Wound Care Pro fe s s i o n a l s
Need to Know the Diffe re n c e
Laura Bolton, P h D ; Pe g gy Dotson, R N , B S ; M o rris D. Ke r s t e i n , M D

O b j e c t i ve s
The reader will be challenged to:
Differentiate between controlled clinical trial evidence of wound care product efficacy and case series or
studies and describe product use
Use 3 sources of evidence on product efficacy and safety in clinical practice
Design a controlled clinical study of wound care product efficacy and safe t y.

Introduction

Definitions and Scope

n keeping with rapid changes in healthcare, wound care

research has made great strides. Product availability has
branched from few options to a multitude of selections
now classified in product categories. Likewise, expectations regarding treatment choices have progressed from it
worked before approaches to research-based decision
making.13 Solid rationale for established or modified treatment plans separates a knowledgeable healthcare provider
from a haphazard one. Given the abundance of published
literature and sales materials, all claiming product superiority, how does one discern the legitimacy of the claims
being made? It is the responsibility of the clinicians on the
interprofessional team not to accept these claims at face
value but to scrutinize the quality of information received
and to use it properly.4 When they can identify the different types of research and understand what conclusions can
be drawn from each, practitioners are better prepared to
base care decisions solely on the accurate [Link] goal
of this chapter is to provide wound care professionals the
tools needed to identify the various types of clinical
research that support wound care product claims and to
select only the legitimate conclusions derived from each as
the scientific backing for their wound care decisions.

Different types of clinical research aid medical decisionmaking in different ways. The US National Institutes of
Health website at [Link] classifies clinical
trials by function:
Treatment trials test new or experimental treatment
modalities, drugs, or approaches to surgery or radiation
therapy
Prevention trials explore modalities, lifestyle change, or
procedures to prevent the onset or recurrence of disease
Diagnostic trials explore improved diagnostic tests or
procedures for a disease or condition
Screening trials optimize detection of diseases or
health conditions
Quality-of-life or supportive care trials explore
ways to improve comfort and other quality-of-life factors for those with chronic illnesses.
Table 1 lists types of clinical study design from strongest to
weakest evidence, with content and conclusions that can be
drawn from each type. More detail can be obtained at
h t t p : / / w w w. ve t m e d . w s u . e d u / c o u r s e s - j m g ay /
[Link] or [Link]
[Link]. Each type of research is valuable if the conclusions are consistent with the study design and methods.

Bolton L, Dotson P, Ke rstein M. Controlled clinical trials versus case studies: w hy wound care professionals need to know the differe n c e. In:
Krasner DL, R o d e h e aver GT, Sibbald RG, eds. C h ronic Wound Care : A Clinical Source Book for Healthcare Pro fe s s i o n a l s. 4th ed. Malvern, Pa : HMP
Communications, 2007:5766.

CHRONIC WOUND CARE, 4th Edition

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Bolton, Dotson, and Kerstein

Controlled Clinical Trials Versus Case Studies

Table 1. Types of clinical research and conclusions that can be appropriately derived from each (beginning with
strongest evidence)
Type of Study

Content

Experimental Studies

Investigator assigns modality

Prospective, randomized
controlled trial5 (RCT)

Prospective comparison of measured

effects of randomized, 2 or more modalities
on patients randomly assigned by
investigators to groups

Comparative safety and efficacy of modalities

evaluated for outcomes measured if groups
were initially similar on all related measures
and risk factors

Prospective, randomized,
crossover trial6

Similar to RCT, except that all groups

receive successive treatments according
to a randomly assigned schedule

Same as for RCT, only this and the RCT

provide evidence of product efficacy and
safety

Prospective, nonrandomized,
controlled trial7

Similar to RCT except that patients are not

randomly assigned to groups

Potentially biased unless groups are

rigorously matched on all relevant
features on enrollment

Observational Studies

Treatments naturally selected

Prospective cohort study8

Measured outcomes are correlated with

treatments or diagnostic modalities
administered prospectively

Correlation between treatments and health

outcomes; useful for testing validity of
diagnostic tools, testing product safety, or
generating hypotheses

Retrospective,
case-control study (RCC)9

Clinical outcomes of the proportion of

cases with 1 risk factor or treatment are
compared to those of patients in the same
population without it

Odds ratios are calculated that a given

treatment or risk factor is associated with
the measured outcome; high potential for
bias; may support product safety in selected
patients

Ecologic (aggregate) study10

Similar to RCC, performed on an aggregate

of multiple, diverse populations

Similar to RCC, with weaker ev i d e n c e

unlike ly to be re l evant to any individual patient

Cross-sectional
(prevalence) study11

Descriptive study of relationship between a

condition (eg, confined to bed) and a health
outcome (eg, having a pressure ulcer) at 1
point in time

Such studies can describe outcome trends

over time but lack information about
exposure to causative factors

Survey of clinical practices or

outcomes over time
(incidence study)12

Information gathered by interview or

questionnaire over a specified period
of time, usually in months or years

Frequency of a specified practice or incidence

of a clinical outcome (eg, nosocomial
pressure ulcers or infections)

Case series13

Description of treatment and outcomes of

a series of patients receiving the same
treatment modality

Weak evidence of safety because patient

selection may be biased; may provide
information on product performance

Case study14

Anecdotal description of 1 patients course

of disease and (ideally) measured outcome

Weakest evidence; describes how others

managed this condition and clinical outcome

The strongest support for decision-making is the randomized, controlled trial (RCT). Hallmarks of a well conducted RCT are that the experimental and contro l l e d
groups are matched on initial laboratory and demographic
values as well as wound characteristics. Retrospective studies should be avoided. They may be biased by omitting
patients who we re discontinued due to pro blems with the
modality or protocol of care. Each type of study described
in Table 1 answers a different kind of question with potentially useful evidence for the interp rofessional team. In the
absence of higher quality evidence, even case studies can
be useful to the wound care team, particularly to introduce
staff to usage or performance of a new product or an existing product on a new indication. However, answering
questions of comparative performance or efficacy re q u i res
a properly conducted RCT or cro s s - over trial. In addition
to individual studies, meta-analyses of all studies that meas58

Conclusions

u re specific outcomes (eg, infection),15 l i t e r a t u re summaries,16 and systematic rev i ews like those cited at the
Cochrane website ([Link] c o c h r a n [Link]) are helpful
in aiding clinical decision-making. If an inadequate scientific basis exists for including a particular treatment modality in ones protocol of care, one can test its comparative
efficacy in achieving measurable goals by conducting a
controlled clinical trial of the treatment versus an accepted
standard or control tre a t m e n t .5,6 Resources abound with
the how-tos of clinical re s e a rc h .17,18 From these, one can
learn more about the different types of re s e a rch and how
to conduct a study.
Whatever type of study is conducted, one should not
focus solely on the wound to the detriment of the patient.
Treating ulcers without proper diagnosis and management
of the patients comorbid conditions or factors that contribute to tissue breakdown is a waste of valuable resources
CHRONIC WOUND CARE, 4th Edition

Controlled Clinical Trials Versus Case Studies

Bolton, Dotson, and Kerstein

Table 2. Evidence reviewed by the FDA in support of wound care products

Product Classification

Product Description

Evidence Required

Class I medical devices are low risk; this

includes most wound dressings and
ostomy supplies

Product is not life supporting or life

sustaining and does not present a
reasonable source of injury through
normal usage21

The FDA has classified wound care

products as low risk and for the most
part do not need premarket approval
before distribution

Class II medical devices are higher risk,

and a majority require data to assure
safety and effectiveness

May support or sustain human life, and

there is enough information for
performance standards

The FDA may examine and identify

controls and tests adequate to assure
safety and effectiveness in a premarket
application (PMA)

Class III medical devices are high risk

for which there is not sufficient
information to place them into a Class I
or II category or to establish
performance standards

Support or sustain human life; are of

substantial importance in preventing
impairment of human health or present
a potential unreasonable risk of
illness or injury

Requires PMA with sufficient, valid,

scientific evidence to assure the device
is safe and effective (clinical studies,
weighing health benefits and risks)

Over-the-counter (OTC) drugbased on

prior research, the FDA has agreed on a
safe, effective ingredient or combination
of ingredients, doses, labeling, claims, and
indications for more than 80 therapeutic
categories

Regulated by FDA based on compliance

to therapeutic monograph labeling21
and the assumption that their benefits
outweigh their risks; potential for misuse
and abuse is low

Safety and efficacy of OTC drugs, such

as skin protectants or certain topical
antimicrobial or antifungal agents, is
based on manufacture to FDA
therapeutic monograph specifications

Prescription drugs include oral or topical

agents requiring a physicians prescription;
this class would include debriding agents
and non-OTC antimicrobial agents

Drugs include substances with

pharmacologic or other direct effect in
the diagnosis, cure, mitigation, treatment,
or prevention of disease or to affect the
structure or any function of the human
body. . .22

Drugs require proof of both safety and

efficacy relative to standard agents or
treatments that may be submitted to
the FDA in a New Drug Application
(NDA) or, in the case of a generic
drug, an abbreviated NDA (ANDA)

and time. All studies from the RCT to the case study
should include normal standard laboratory values while
also assuring that the patients had adequate nutrition (eg,
pre a l bumin or albumin for protein sufficiency, transferritin
for iron transport from the gastrointestinal tract), we re not
immunosuppressed by virtue of a normal lymphocyte
count, and had controlled blood glucose as indicated by a
normal hemoglobin A1c for patients with diabetes. Pa t i e n t s
should have adequate hydration and renal function, and
their disease state(s) should be under control sufficiently to
allow wound healing before they are enrolled in the study.
Even the best controlled clinical study cannot diagnose and
manage the cause of a chronic wound; this re q u i res an
interp rofessional team.
Research also should be clinically re l evant if it is to support conclusions that have bearings on healthcare practice.
The more similar to ones own clinical practice a study is in
setting, wound type, patient, and treatment variables, the
more clinically re l evant it is to ones use and decisionmaking process. Though the scope of this chapter includes
only clinical studies, remember too a wealth of preclinical
research exists that also can aid decision-making to the
extent that it is clinically re l evant to ones practice. In-vitro
studies are the least clinically re l evant because they are based
on responses by cells in culture, separated from their normal
environment rich in growth factors, enzymes, and other natCHRONIC WOUND CARE, 4th Edition

urally occurring molecules in the body. In-vivo studies on

animals can be especially valuable when they parallel clinical phenomena (eg, acute animal wound healing parallels
that of humans; pressure-ulcer animal models simulate
human pre s s u re ulcers;19 and ischemic ulcers can be generated in animals by prolonged ischemia).20 Clinical re l evance
should be carefully assessed before extrapolating from animal
to human studies, or when generalizing from one type of
clinical wound to another (eg, from donor sites to diabetic
foot ulcers). Animal models for chronic wounds, such as
those mentioned previously, a re more clinically re l evant to
chronic wounds of similar morphology and etiology than a
human acute wound, such as a donor site, would be.
However, the most re l evant research on which to base clinical wo u n d - c a re decisions is the controlled clinical study of
patients similar to those who receive the care. Most pro f e ssionals turn to controlled trials on the etiologies and depths
of wounds they manage, when available, as a basis for pro t ocol choices because of the question of clinical re l evance.
Conducting a controlled clinical trial is not as forbidding
as it sounds. It can be fun and open new horizons of patient
care and communication with colleagues. Getting involved
in some form of research helps the new researcher learn the
process. However, a basic understanding of various research
models is essential in establishing the foundations for clinical practice.A format for conducting research follows in this
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Bolton, Dotson, and Kerstein

chapter. This chapter discriminates between the 2 most

common types of studies reported: uncontrolled case or
product studies and controlled clinical [Link] this
basic knowledge, readers will be able to use the evidence
they glean from published and unpublished professional and
sales literature with a clear understanding of exactly what
each form of evidence means for their practices and their
patients well being.

Making the Most of Av a i l a ble Evidence

Evidence for product safety and efficacy already may have
been rev i ewed by government authorities or by other pro f e ssionals in search of answe rs .This evidence may be available in
product package inserts, in the published literature, in posters
or presentations at professional meetings, or in unpublished
product literature. Whatever the source, the aforementioned
tools and definitions will help the clinician draw his or her
own conclusions about the clinical re l evance, safety, and efficacy of products based on available literature.
Product package inserts. In the United States, the
Food and Drug Administration (FDA) reviews supporting
evidence for claims, indications, warnings, and contraindications before giving clearance to market for some wound
care products. Different classifications of products require
different supportive evidence before they can be marketed
(Table 2). Understanding these requirements for each class
of product helps wound care professionals to be aware of
the research base that already exists for each product and
helps one interpret marketing claims of relative efficacy or
confidently request evidence to support these claims.
Evidence ava i l able from industry. Food and Drug
Administration clearance to market most wound dressings
is based on substantial equivalence to another dre s s i n g ,
preclinical safety studies, and assurance of consistent quality, but it does not support conclusions of clinical pro d u c t
performance or re l a t ive efficacy of the product.21,22 In
some cases, studies of clinical performance characteristics
may have been performed for a wound care device to
e s t a blish substantial equivalence to another dev i c e, but
these are not required. In general, it is not safe to assume
a wound care dressing has been tested clinically before it
is marketed unless the company provides that ev i d e n c e
with the product literature. In the absence of published
clinical evidence, wound care professionals are encouraged
to contact companies that market the devices for ev i d e n c e
supporting product claims.
Comparative efficacy studies of most wound care devices
also are not required before marketing clearance is given.
For example, if manufacturer C develops an alginate dressing substantially equivalent to manufacturer Bs alginate
dressing, manufacturer C may produce and market its alginate dressing in compliance with regulations without con60

Controlled Clinical Trials Versus Case Studies

ducting a clinical study on its own alginate dressing.

Manufacturer C may use the substantial equivalence property to support clinical performance, using the same references pioneered by manufacturer B to support product Cs
claims, even if product C was never used on clinical
wounds. This practice benefits society by encouraging
choices in each dressing category and reducing costly
research. However, wound care professionals should not
assume that supporting evidence exists for relative clinical
performance of the 2 alginates. If assertions are made about
comparative clinical efficacy of the 2 dressings, references
should be provided in the associated [Link] professionals will review these references for accuracy or request
them from the company for verification. Evidence supporting comparative clinical claims can be provided only by a
clinically relevant evaluation that compares the 2 dressings.
Evidence from literature and professional meetings. In addition, independent or corporate-sponsored
research may provide evidence for wound care decisions
beyond that evident from product package inserts and routine FDA-required data. These can be acquired by reading
or searching the wound care literature, networking with
other wound care professionals, attending professional
meetings, and critically reading posters. If the evidence is
not available from any of these sources, resourceful wound
care professionals can do their own research to answer questions about how wound treatments perform, their optimal
use, and which treatment modalities work best.23

Format for Conducting a Research Study

Specifically, research is investigation or experimentation
aimed at the discovery and interpretation of facts...24 An
attempt to answer any question can be considered research.
If good scientific method is used to attain the answer, it will
predict patient outcomes accurately and [Link] format
for the process of conducting research normally proceeds
through the following stepssimilar to those involved in
building a house:
Formulate the question to be answered (decide on the
function, type, and location of the house)
Search prior literature on the question (assess the site and
prepare the foundation)
Develop this question into a specific objective for study
(devise a general plan)
Write the protocol (draw the blueprint)
Set up the study (obtain a building permit)
o Obtain resources, such as funding, equipment, and
properly licensed personnel on the interprofessional
team required to conduct the study
o Obtain permissions and approval for the study protocol from appropriate supervisors and the institutional
review board (IRB)
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Bolton, Dotson, and Kerstein

Questions

Literature Search

Objective
Compare treatment effects
Types of wounds
Outcomes explored

Objective
Describe treatment effects
Types of wounds
Outcomes explored

Methods
Patients included/excluded
Time line:
Retrospective
Prospective
Setting
Good clinical practice
Treatment applications and duration
Follow-up
Clinical Evaluation

Case Study

Design

Controlled
Experimental vs. standard protocol
Randomized, stratified
Randomized
Nonrandomized

Uncontrolled
Experimental protocol only

Results measured
Valid, reliable
Comparative analysis
Clinically relevant to objective

Results measured
Valid, reliable
Before/after analysis
Clinically relevant to objective

Conclusions
Experimental is/is not safe and
efficacious vs. standard protocol

Conclusions
Product or protocol safety
Performance to use

Figure 1. Differentiating controlled clinical evaluations from case studies.

Conduct the studyapply treatments and observe and
record the effects (build the house)
Analyze the results (certify that the structure meets codes
for occupancy)
Write up the conclusions so others can benefit
(enjoy/assess the house).
These steps have been described in greater detail elsewhere.4,17,22 They will be used here to illustrate the differCHRONIC WOUND CARE, 4th Edition

ences between clinical evaluations and case studies (Figure 1).

Research begins with a question. The answer will add
information to the foundation of knowledge about that
question. Be sure to ask a clear, narrow question that will
determine a research objective feasible to answer using the
resources and subjects at hand. A literature review will help
you assess the research environment to build on a secure
foundation of others [Link] research objective deter61

Bolton, Dotson, and Kerstein

mines the outcome and setting of a study in much the same

way that initial choices of function, type, and site shape a
[Link] site must be consistent with the anticipated purpose and structure. A researcher will need to select the
questions to ask in order to determine the study methods.
For example, in an environment subject to frequent flooding, it may be prudent to build the house on stilts.
Knowledge regarding the use and construction of the stilts
is acquired by re f e rring to previous experience. The
researcher will find this experience by searching the literature related to his or her topic. Just as the environment and
past experience influence a buildings structural design, a
literature review helps the researcher refine the question,
select the most useful methods to answer it, and build on
the established body of scientific evidence.
With a clear question or objective in mind, the
re s e a rcher can formulate a focused research objective,
specifying the type of wound, patient, setting, treatment,
and measured outcomes. Just as a weak foundation eventually results in instability of the stru c t u re, an unclear
o b j e c t ive can lead to weak or unclear results. A clear
re s e a rch objective is the foundation of the studys general
plan, described in detail in the study protocol or design.
The study protocol specifies the inclusion/exclusion criteria, treatments, treatment duration, va ri a bles measure d ,
and anticipated analysis. Just as the bl u e p rint of a house
must be precise and clear and match the owners vision,
the study objective and protocol must clearly and accurately address the investigators question in order to derive
re l evant answers at the end of the study.
Before setting up a study for market-approved products,
the researcher should read the product package insert(s) for
the material(s) carefully, making sure that the products have
been cleared by the FDA or an equivalent agency for use
on the type(s) and depth(s) of wound(s) being studied. If
asked by a manufacturer to perform a study investigation
for FDA approval to market the product, the protocol and
indications are all reviewed and approved by the FDA and
the researchers own IRB before study commencement. If
a manufacturer requests an investigation of a marketed
product for an unapproved indication, the clinician is legally responsible for adverse events. Manufacturers may sponsor studies only for FDA-cleared indications of their products.4 If this is not the case, the researcher and his or her
institution bear responsibility if using the product outside
normal indications.
Approvals and permissions can provide valuable tools for
the success of a study, assuring access to experts in study
design and conduct. Facilities, whether acute care hospitals,
long-term care facilities, or home health agencies, either
have their own IRB or have access to one. The IRB regulates research to assure safety and ethical standards. It is pru62

Controlled Clinical Trials Versus Case Studies

dent before initiating any investigation to check IRB

requirements. The degree of IRB involvement in a protocol may be influenced by whether the evaluation is experimental or involves further study of an already approved
indication. Experimental testing invo l ves pre m a r keted
products or a marketed product for indications that have
not been approved. One additional approval to obtain is
that of the patient. Guidelines regarding the necessary
informed patient consent are also obtainable from the IRB.
Patient-informed consent is more than a formality; it is the
patients right, guaranteed by the Helsinki Accord, and a
cornerstone of quality research by assuring patient understanding of and compliant participation in the study. By
informing and gaining support of colleagues and the facilitys administration, the researcher will also garner cooperation and moral support from individuals who may provide
valuable assistance, feedback, and tips on valid, reliable techniques for measuring or conducting the study. Additional
resources of financial support and materials may include
government agencies and corporations.4 Just as a building
permit assures cooperation by ascertaining conformance to
local codes and standards, these approvals help to assure the
study conforms to good clinical practices and the specific
standards of the researchers professional environment.
Conducting the study with integrity and diligence is
another key to success. As the strength and quality of a
house depend on builder adherence to the blueprint, so too
does a well conducted study follow its protocol as closely as
possible. Anyone involved in the study requires adequate
training to assure uniform treatment application, patient
monitoring, and measurement of outcomes. All professionals should keep patient welfare as the highest priority while
conducting the study.
Comparing case studies with RCTs. Early phases of
the research process do not differ for case studies and clinical [Link] question sends the curious re s e a rcher to
the literature to explore and learn from the experience of
prior researchers. However, the objective of a case study,
which explores effects of a single treatment, is clearly different from that of a clinical evaluation, which compares mu ltiple treatments. If the objective is to determine product
safety or to describe performance, effects of a single tre a tment will be explored on a given wound care outcome in a
case study paradigm. Case studies are time-honored vehicles
for informing colleagues about unusual responses or adverse
reactions to treatment modalities. For example, many journals feature special sections for case studies, which spawn
new research and alert professionals to new clinical findings.
If comparative efficacy is to be determined, 2 or more
treatment groups will be compared in a clinical evaluation of
their comparative effects on the specified outcome(s). The
protocol will specify the treatments to be compared and
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Controlled Clinical Trials Versus Case Studies

techniques for applying each treatment and measuring [Link] study design flows from the objective. Ideally, the
treatments will va ry in only 1 aspect of care, and patients will
be assigned in a random or other unbiased way to each tre a tment group. In a well-designed clinical evaluation, wound
and patient characteristics are measured before and after
treatment for a given duration to allow conclusions about the
comparative safety and/or efficacy of the treatments applied.
The process of setting up and conducting the study is
similar for clinical evaluations and case studies. Both require
resources, materials, and cooperation of, or permission
from, the IRB, administration, colleagues, and patients in
order to succeed in meeting their objective. Including a
functioning interprofessional team in the research process is
vital to the success of patient management25 and is a hallmark of a well-managed clinical study.
Analysis of results for a case study involves descriptive
statistics before and after treatment of the following:
Patient variables (eg, age, sex, mobility, nutritional status,
risk factors)
Wound variables (eg, area, depth, necrosis, exudate, surrounding skin, pain)
Environmental elements (eg, caregiver, financial constraints, footwear).
If more than 1 patient completes the study, paired statistics
can be used to compare pertinent measures before, during,
and after treatment and optionally after a follow-up period
specified in the [Link] process provides readers with a
conclusion of product or protocol safety during treatment as
well as durability of its effects. Clinical evaluations compare
these 3 types of variables for the treatment groups studied,
which assures similarity before the experimental and control
treatments or procedures are implemented. Next, the differences in the progressive treatment effects on these variables
as well as the subsequent durability of these effects during
follow-up intervals are measured. Comparative statistics, such
as t-tests or analyses of variance, are used for the continuous,
normally distributed variables, whereas chi-square or other
nonparametric statistics are used for discrete or skewed data.
The results yield direct information about differences in
effectiveness of the treatments.
Conclusions derived from a case study re p o rt the course
of events when 1 or more participants use a product or
procedure. For example, Wilson et al13 performed a longitudinal (over time) study of 7 patients with systemic
methicillin-resistant Staphylococcus aureus (MRSA) infections whose leg ulcers were dressed with hydrocolloid
dressings. All patients we re isolated to prevent the spread of
this pathogen until its presence was detected only in the
[Link] the dressing isolating the wound, the patients
resumed normal hospital-room residence without spre a d
of the MRSA, which eventually disappeared in all but 1
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Bolton, Dotson, and Kerstein

patient.W h e reas the study established safety of the product

on microbially contaminated wounds, it did not extrapolate comparative efficacy of the treatment because it was
not compared to an alternative treatment method. By
establishing product safety, the case study may set the stage
for further investigations to compare this treatment modality to other management methods.
Although safety questions are wo rt hy research objectives to
address, many professionals want more than assurances of safety for their wound care products. For instance, when making
selections in the building scenario, 2 brands of window shades
viewed individually may visually keep out the suns rays.
However, only by comparing them under the same sun exposure at the same time of day and using a thermometer to
obtain an accurate temperature can one ascertain which window shade provides more protection against the heat. Both
brands work, but which one is more effective? In a wound
care study, after safety is established, research answe rs questions
about issues, such as comparative efficacy of healing, d e b ri d ement, and pain relief, by comparing products under similar
conditions side-by-side or in parallel to control treatments.
The more specific the investigation is to the condition of
intended product use, the more accurate and clinically re l evant the results will be. Results are only as good as the re l i ability (repeatability) and validity (clinical relevance) of the
methods by which they are obtained and may apply only to
the original objective set out to be discovered. One must be
careful to generalize only to the kind of population studied.
For example, if an objective is stated to determine the comparative efficacy of 2 enzymatic debriding agents in removing
necrotic tissue from pressure ulcers , the conclusion may generalize only to pressure ulcers, not to arterial ulcers , because
they were not included in the evaluation. Research, like
building a house, must proceed in specific sequence of clearly designated steps, without omitting a single step or exceeding its intended boundaries, if its integrity is to be maintained.

Conducting Your Own Study

With the framework of a literature search-based question
and objective established, what are the details that direct the
outcomes? This is where the customizing (interior design)
takes place, which will differentiate case studies from product evaluations. The following need to be included in a
research design in order to produce sound results.
Study design and methods. Inclusion criteria identify who is being studied (eg, nu rsing home residents with
sacral pressure ulcers). Relevance of medications, disease
processes, patient status, age, gender, etc. varies according to
the objective. Narrow inclusion criteria limit the number of
variables influencing the outcome but will also limit general
applicability of the results. Exclusion criteria identify patients
not studied to whom the results cannot be generalized.
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Bolton, Dotson, and Kerstein

The number (N) of participants contributes to the power

of the [Link] more participants included, the more credible the results will be at the completion of the investigation. Obviously, the reported safety of a product after 350
applications is more convincing than a report on 25 applications. The number of participants also affects the statistical significance when the results are analyzed for differences
in treatment effects on the wounds. For a given magnitude
of difference in treatment effects, the more patients in a
study, the lower the probability that the observed difference
resulted from chance [Link] statistical significance, or
alpha probability, sometimes called P, is the probability of
incorrectly concluding that the treatments caused different
effects on the wounds studied.
The setting should be relevant to the objective. For
instance, is the researcher comparing the practicality of 2
different products in the home environment? If so, common sense would determine that the study should take
place in the participants homes. Otherwise, extrinsic factors
may influence the relevance of the results.
All research re q u i res a method of data collection that is
reliable, valid, and objective. Reliability refers to a method of
data collection that achieves consistent, repeatable, and accurate results of observations. If data collection is reliable, it can
be replicated accurately at different times by the same
observer or by another observer. An evaluation should use
valid tools that actually measure the clinical outcome being
investigated. Observations must be measurable in order for
the study to be objective. For instance, if the participants
degree of risk for developing a pressure ulcer is determined
solely by the investigators assessment rather than with the use
of a valid, re l i a ble tool, the observations are not likely to be
accurately duplicated, which reduces data reliability.
What data collection timeline is used? A retrospective
study examines specified past events during a given period
of time. Retrospective studies are commonly conducted by
means of chart reviews. P recise records are essential for accurate data collection. In a simple illustration, a retrospective
study using length x width as the healing measures must
have these measurements recorded consistently at regular
timeframes for all wounds assessed. Prospective research,
however, evaluates that which will take place. The research
design is based upon an objective, and participants are
accrued or actively enrolled into the study. If the timeline
selected is pro s p e c t ive, the researcher must determine
whether the study will be controlled or uncontrolled.
The control refers to the gold standard of the treatment
protocol. This standard is usually the best known or most
widely used method of care. An uncontrolled or case study
investigates the performance of a new product without
comparing it to a standard protocol. It could also examine
the use of an established procedure in a new situation.
64

Controlled Clinical Trials Versus Case Studies

Under either circumstance, the experiment can conclude

only that the product or procedure is safe. All participants
included in an uncontrolled study (product or case study)
re c e ive the same treatment pro t o c o l . No comparison
against another product or procedure takes place; therefore,
no conclusions regarding superior efficacy versus that of
another product or procedure can be claimed.A product or
case study is beneficial in providing the professional information regarding product use, performance, and outcomes,
such as ease of use. Properly designed and appropriately
reported, such case studies can provide valuable information
to assist in decision-making and deciding whether or not
further research is needed.
On the other hand, a controlled clinical trial utilizes
comparisons and carries more power by discerning both
safety and comparative efficacy of a product or pro c e d u re.
H e re, the objective is to evaluate the experimental pro d u c t
or procedure against a standard control. Depending on
re s o u rc e s , funding, time, and participant availability, e x p e rimental and control treatments may be applied to differe n t
patients, to different wounds on the same patient, or, if
appropriate, to different parts of the same wound. The
re s e a rcher must commit to a lengthy patient accrual
p rocess to obtain a significant number of patients for a
controlled study in treatment of rare diseases, such as
necrotizing fasciitis, w h e reas a controlled study of pre s s u re
ulcers in a nursing home may take less time because the
latter are more abundant.
Patient or wound assignment. When using a control,
the method of participant assignment must be determined.
Nonrandomized treatment assignment allows the investigator to determine what treatment is used on which participant. Although this permits treatment comparison, it introduces a bias into the evaluation thereby influencing objectivity and affecting outcomes. A less biased, more powerful
assignment method is randomization. Webster defines random as being or relating to a member of a set whose
members have an equal probability of occurring.24
Therefore, patients will have equal probability of being
assigned to each treatment group according to a preselected random pattern, thus eliminating investigator bias. A
stratified random pattern further defines subgroups and
randomizes treatment assignment accordingly.15 Fo r
instance, 2 treatment groups of trochanteric pressure ulcers
may each be subdivided into age-related subgroups, and
treatments are then randomized within each subgroup so
that half the patients over 65 years of age are randomly
assigned to receive each treatment, half the patients 45 to 65
years are similarly assigned to treatments, as are half the
patients younger than 45 years.
Evaluation of results. Unbiased evaluation of results
improves the accuracy of a study. This is done in a blinded
CHRONIC WOUND CARE, 4th Edition

Controlled Clinical Trials Versus Case Studies

evaluation or experiment. A single-blinded evaluation is

when the subjects are unaware of whether they were
assigned to the control or experimental group or procedure.
In contrast, a doubl e - blinded experiment obscures know ledge of control versus experimental assignment from both
the subject and the investigator who evaluates the outcomes.
This significantly reduces the possibility of opportunistic
biases during treatment and outcome measurement.
Analyzing and reporting results. The results should
only cover the outcomes cited in the study objective, no
more or no less. The data re p o rted are obtained strictly by
the investigation and not surm i s e d .Validity and reliability of
outcome measures determine the quality of the results. Do
the outcome measures address the original objective? A well
conducted study should also measure and re p o rt product
impact on quality of life and costs of care, including cost
effectiveness if feasible. This information can inform you
about what types of patients and settings may be optimal for
the product(s) [Link] the nu m b e rs of patients sufficient
to give power to results? The results section should contain
the appro p riate analysis of all variables recorded, beginning
with a section ascertaining that the treatment groups were
initially similar on pertinent patient characteristics, such as
wound size, duration, and [Link] key tests for differe n c e s
in treatment effects should be appropriate to the data and on
independent subsets of [Link] should be presented succinctly in figures and tables that clearly illustrate the level of
statistical significance of findings. Treatment details should
vary only relative to treatment [Link] comparing 2
primary dressings, the dressings themselves are ideally all that
should differ. Cleansing procedures, secondary dressings, and
taping methods should be equivalent in order to isolate the
specific dressing as influencing the outcome. Procedures
associated with 1 treatment but not the other could cause
differences in patient outcomes erroneously attributed solely to the treatments.
Finally, the conclusion is the summation of the study.
Although the conclusion is based on the investigators
interp retations of the results, it should still accurately
reflect the results obtained and not include assumptions.
One cannot assume in the conclusion that the re s u l t s
a p p l i c a ble to the population studied can generalize to the
excluded group or to other settings.4 For example, if the
e f f e c t iveness of a pre s s u re - reduction surface is establ i s h e d
in a hospital setting, it cannot be assumed that the re s u l t s
apply to the home-care population. Caregiver time and
training level in critical are a s , such as repositioning or
pre s s u re relief, may va ry from setting to setting.

Bolton, Dotson, and Kerstein

decisions. This re s e a rch may be in the form of publ i s h e d

or unpublished literature or studies conducted within
ones own institution. W h a t ever the sourc e, only knowledge and application of the research process can help one
derive or interp ret quality information to improve
patient [Link] make the most of this information, a wise
wound care professional will scrutinize the results as well
as the conclusions that can be legitimately drawn fro m
the context of the research design:
A re the results consistent with the objective and
method?
Do efficacy claims need to be discounted because the
study was uncontrolled?
R e s e a rch need not be intimidating. Become familiar
with the floor plan, start at the ground, and build up. Set
realistic goals that will support your clinical practice. It is
important to remember that re s e a rch objectives will not
always culminate in a final answer but may lead to another question. In the context of wound and skin care, case
studies and case series may provide early evidence of product safety and descriptive functions, but only controlled
clinical trials ideally support final decisions about the best
treatments to use in achieving wound care outcomes.

Acknowledgment
The authors wish to acknowledge the work of Geraldine
Mayoros in providing graphics for this manuscript.

Take Home Message for Practice

Responsible clinical professionals on wound care
teams will scru t i n i ze product indications, claims, and
supporting literature and recommend only products
supported by the strongest and most clinically relevant evidence.

Self-Assessment Questions
[Link] is stronger evidence of product efficacy?
A. Pro s p e c t ive, randomized, controlled study on 20
patients
B. 20 clinical cases
2. Most wound care products do not need premarket
approval before distribution.
A. True
B. False

Summary
T h rough scientific re s e a rc h , the wound care pro f e ssional is able to make informed, know l e d g e a ble tre a t m e n t
CHRONIC WOUND CARE, 4th Edition

Answers: 1-A, 2-A

65

Bolton, Dotson, and Kerstein

Controlled Clinical Trials Versus Case Studies

Refe re n c e s
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CHRONIC WOUND CARE, 4th Edition