CASE STUDY

Control in the Design of an Experiment

Dr. Penelope Nicholls is interested in exploring a possible
connection between high plasma homocysteine (a toxic
amino acid created by the body as it metabolizes protein)
levels and cardiac hypertrophy (enlargement of the heart)
in humans. Because there are many complex relationships
among human characteristics, it will be difficult to answer
her research question because there is a significant
risk that confounding factors will cloud her inferences.
She wants to be sure that any differences in cardiac
hypertrophy are due to high plasma homocysteine levels
and not to other factors. Consequently, she needs to design
her experiment carefully so that she controls lurking
variables to the extent possible. Therefore, she decides
to design a two-sample experiment with independent
sampling: one group will be the experimental group, the
other a control group. Knowing that many factors can
affect the degree of cardiac hypertrophy (the response
variable), Dr. Nicholls controls these factors by randomly
assigning the experimental units to the experimental or
control group. She hopes the randomization will result in
both groups having similar characteristics. ESRD patients into their study. All these patients
In her preliminary literature review, Dr. Nicholls were on hemodialysis for between 6 and 312 months.
uncovered an article in which the authors hypothesized The control group subjects were chosen so as to
that there might be a relationship between high plasma eliminate any intergroup differences in terms of mean
homocysteine levels in patients with end-stage renal blood pressure (BP) and gender. In an effort to minimize
disease (ESRD) and cardiac hypertrophy. She has asked situational contaminants, all physical and biochemical
you, as her assistant, to review this article. measurements were made after an overnight fast. The
Upon reading the article, you discover that the results of the clinical characteristics and the biochemical
authors used a nonrandom process to select a control findings for the control and ESRD groups are reproduced
and an ESRD group. The researchers enlisted 75 stable in the following tables:
 Case Study 587

Clinical Characteristics (Mean t Standard Deviation)

Parameters Controls (n ⴝ 57) ESRD Subjects (n ⴝ 75)
Age (years) 49.2 { 14.7 57.3 { 15.1
Sex (M/F ratio) 1.4 { 0.50 1.4 { 0.50
Body surface area (m ) 2 1.85 { 0.25 1.67 { 0.20
Body mass index (kg>m ) 2 26.0 { 4.70 23.7 { 3.90
Systolic BP (mmHg) 145.0 { 15.5 148.8 { 29.7
Diastolic BP (mmHg) 85.0 { 14.8 80.2 { 14.3
Mean BP (mmHg) 104.5 { 14.2 103.6 { 17.4
Pulse pressure (mmHg) 59.4 { 15.5 68.6 { 24.3
Heart rate (beats/min) 63.0 { 8.0 70.0 { 9.0

Biological Findings (Mean t Standard Deviation)

Parameters Controls (n ⴝ 57) ESRD Subjects (n ⴝ 75)
Total cholesterol (mmol/L) 5.28 { 1.04 4.91 { 1.06
HDL cholesterol (mmol/L) 1.38 { 0.39 1.07 { 0.38
Triglycerides (mmol/L) 1.39 { 0.63 1.90 { 1.02
Serum albumin (g/L) 44.7 { 2.60 39.9 { 3.00
Plasma fibrinogen (g/L) 3.21 { 0.78 4.75 { 1.04
Plasma creatinine (mmol/L) 0.10 { 0.01 0.90 { 0.13
Blood urea (mmol/L) 6.10 { 1.20 24.3 { 2.00
Calcium (mmol/L) 2.46 { 0.08 2.45 { 0.12
Phosphates (mmol/L) 1.03 { 0.21 1.88 { 0.38
Source: Jacques Blacher et al., “Association between Plasma Homocysteine Concentrations and
Cardiac Hypertrophy in End-Stage Renal Disease.” Journal of Nephrology 12(4): 248–255, 1999.
Article available at www.sin_italia.org/jnonline/vol12n4/blacher/blacher.htm.

Which type of sampling method, independent or
dependent, was used in this experiment? Explain.
Using the appropriate hypothesis-testing procedure,
determine whether the control and ESRD groups have
equivalent population means for each of the various
clinical and biochemical parameters. Dr. Nicholls requires
that you indicate those parameters that have P-values less
than 0.05 and those less than 0.01.
Detail any assumptions and the rationale behind
making them that you made while carrying out your
analysis. Is there any additional information that you would
like to have? Explain. Are there any additional statistical
procedures that you think might be useful for analyzing
these data? Explain.
Based on your findings, does it appear that the control
and ESRD groups have similar initial clinical characteristics
and biochemical findings? Does it appear that the authors
of this article were successful in reducing the likelihood
that a confounding effect would obscure their results?
Even though Dr. Nicholls does not wish to restrict
her research to patients with end-stage renal disease, how
might the information presented for this research assist her
in designing her own experiment?
Submit a written report to Dr. Nicholls that outlines all
your findings and recommendations.