Summaries
14th
June 2010
Session 1.5
Case Study - AIDSVAX: A Prophylactic (Preventative) AIDS
Vaccine
Conventional
theory concerning AIDS views HIV as a virus that causes the onset of AIDS by
inducing immune system suppression and failure. One approach may seek to
prevent AIDS cases by preventing HIV infection, by using a vaccine based on
HIV. Consider the description of clinical trials evaluating the first such a
vaccine,
Vaccine
X1{ VX1tm }.
Sketch
out a clinical trial design for Vaccine VX1.
Describe
the treatments, and the outcome(s) by which the treatments will be evaluated.
The
active treatment is the experimental vaccine, VX1. If there are no proven
vaccines available, then the other treatment is placebo.
Do we
want a basic, or comparative trial ?
Since
VX1 is the first vaccine of its class, we want a basic clinical trial, which
uses a placebo for comparison.
Identify
the subject population for this trial.
Subjects
eligible for this trial must by HIV negative, that is, free of HIV infection.
Subjects eligible for the trial must volunteer and give informed consent in
order to participate in the trial.
Discuss
the assignment of subjects to the treatments in the trial.
Enrolled
subjects are randomly assigned to either VX1 or to its placebo version. Neither
the subjects nor the clinical workers will know which drug has been assigned –
this is called double blinding.
We
will track the trial subjects in both treatment groups for a number of
outcomes:
Safety
– any adverse reactions to the vaccine
Effectiveness
– HIV infection status for each treatment group.
Case
Study - Taxol: Terminal Cervical Cancer
Taxol®
was discovered at Research Triangle Institute in 1967 when Dr. Monroe E. Wall
and Dr. Mansukh C. Wani
isolated the compound from the Pacific yew tree, Taxus
brevifolia, and noted its anti-tumor activity in
a broad range of rodent tumors.(1)
Striking
clinical results with advanced ovarian cancer were reported by The Johns
Hopkins University School of Medicine in The Annals of Internal Medicine
in 1989. In 1991 Dr. Samuel Broder, then director of
the National Cancer Institute, hailed Taxol as the
most important new cancer drug in the past 15 years. In December 1992 the FDA
approved Taxol for refractory ovarian cancer.
Today
it is used for a variety of cancers, including ovarian, breast, non-small-cell
lung, and Karposi's sarcoma. The drug is being tested
against a variety of other cancers
Originally,
the only source of Taxol was the Pacific yew; to
treat one patient required the harvest of six, 100-year-old trees. Today, the
drug is made by a semi-synthetic process from Taxus
baccata. 
(1)
M.E. Wall and M.C. Wani, Paper M-006, 153rd National
Meeting, American Chemical Society (1967).
Consider
a clinical trial in which Taxol is evaluated as an
end-stage treatment for Cervical Cancer(2) Sketch this clinical
trial.
(2)
Subjects must be diagnosed with cervical cancer and be assessed with 18 months
or fewer survival time by their oncologist.
Describe
the treatments, and the outcome(s) by which the treatments will be evaluated.
The
active treatment is Taxol. Since these are end stage
patients, the risks associated with conventional cancer treatments are not
worth the dubious possible benefits. We will be using a placebo version of Taxol for comparison.
Do we
want a basic, or comparative trial ?
We
want a basic clinical trial, which uses a placebo for comparison.
Identify
the subject population for this trial.
Subjects
eligible for this trial must be terminal. End stage cervical cancer patients.
Subjects eligible for the trial must volunteer and give informed consent in
order to participate in the trial.
Discuss
the assignment of subjects to the treatments in the trial.
Enrolled
subjects are randomly assigned to either Taxol or to
its placebo version. Neither the subjects nor the clinical workers will know
which drug has been assigned – this is called double blinding.
We
will track the trial subjects in both treatment groups for a number of
outcomes:
Safety
– any adverse reactions to Taxol
Survival
Time and Survival Status
Status
of Cancer
Pain
Quality
of Life
From http://clinicaltrials.gov:
Study Phase (FDA Clinical Trials)
Most clinical trials are designated as phase I, II, or
III, based on the type of questions that study is seeking to answer:
In Phase I clinical trials, researchers test a new drug or treatment in a small
group of people (20-80) for the first time to evaluate its safety, determine a
safe dosage range, and identify side effects.
In Phase II clinical trials, the study drug or treatment is given to a larger
group of people (100-300) to see if it is effective and to further evaluate its
safety.
In Phase III studies, the study drug or treatment is given to large groups of people
(1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to
commonly used treatments, and collect information that will allow the drug or
treatment to be used safely.
These phases are defined by the Food and Drug
Administration in the Code of Federal Regulations.
Clinical Trial Worksheet
From here:
Case Two | Clinical Trial
Sketch | Non-small Cell Lung Cancer (NSCLC)
A key ability of malignant cells is the ability to
induce angiogensis, the formation of new blood supply.
These cells can release a substance that stimulates the formation of new blood
vessels. This ability is key in the ability of malignant tumors to survive and grow.Avastin is a monoclonal antibody that works by attaching to
and inhibiting the action of vascular endothelial growth factor (VEGF) in
laboratory experiments. VEGF is a substance that binds to certain cells to
stimulate new blood vessel formation. When VEGF is bound to Avastin, it cannot stimulate the formation and growth of
new blood vessels. A number of cancers
are driven by the derangement of cells composing the linings (epidermal cells)
of various organs in the body. In particular, these cells lose control of their
growth behaviors, leading to uncontrolled reproduction of cells. This deranged,
accelerated cell reproduction is key to the ability of malignant tumors to
grow.
Tarceva (erlotinib) is an oral
anti-cancer drug under development by OSI Pharmaceuticals, Genentech and Roche.
It is a member of the epidermal growth factor receptor (EGFR) inhibitor class
of agents. Two general types of lung cancer exist: Non-Small Cell Lung
Cancer (NSCLC) and small-cell lung cancer (SCLC). The most common type of
lung cancer is NSCLC. Approximately 85% of all lung cancer cases are NSCLC.
Three main types of NSCLC - General treatment options for each of these are the
same: Squamous cell carcinoma. Most often
related to smoking. These tumors may be found in the mucous membrane that lines
the bronchi. Sometimes the tumor spreads beyond the bronchi. Coughing up blood
may be a sign of squamous cell NSCLC. Adenocarcinoma
(including bronchioloalveolar carcinoma).
Most often found in nonsmokers and women. Cancer is usually found near the edge
of the lung. Adenocarcinoma can enter the chest
lining. When that happens, fluid forms in the chest cavity. This type of NSCLC
spreads (metastasizes) early in the disease to other body organs. Large-cell undifferentiated carcinoma.
Rare type of NSCLC. Tumors grow quickly and spread early in the disease. Tumors
are usually larger than 1-1/2 inches.
First-line
Treatments for NSCLC: Surgery:
Removes the tumor. This can be done if the tumor is small and has not spread to
other areas of your body. Radiation: Destroys any leftover cancer cells
not removed by surgery. This may be done before surgery to make it easier to
remove the tumor. Radiation can also be done after surgery. Chemotherapy
may help slow the growth of cancer cells and destroy them. Chemotherapy may be
used with radiation to help shrink the tumor before surgery. It may be used
after surgery or radiation to destroy any cancer cells that may have been left
behind.
Consider
patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC)
after failure of at least one previous chemotherapy regimen. Consider two treatments: Avastin+Tarceva
and Tarceva. Sketch a comparative clinical
trial for Avastin+Tarceva versus Tarceva in the treatment of patients with locally
advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) after failure of
at least one previous chemotherapy regimen.
We recruit subjects with with locally advanced or metastatic
Non-Small Cell Lung Cancer (NSCLC) after failure of at least one previous
chemotherapy regimen. Those who give informed consent and who qualify are
enrolled in the trial.
Enrolled subjects are randomly assigned to either Tarceva + Avastin (TA) or to Tarceva + PalceboAvastin (T) with
double blinding, so that neither the subjects nor the trial workers know the
actual treatment status of the subjects.
Subjects are followed for safety and toxicity, including kidney or
liver damage.
Subjects are followed for their cancer status – has the cancer
stabilized? Has it spread further? Has it receded? Is the cancer more
treatable?
Subjects are followed for mortality and time-to-death. Do fewer
subjects die in the TA group relative to the T group? Do those who die live
longer in the TA group relative to the T group?
Subjects are followed for quality of life – are subjects in the TA
group better able to live normally and to manage their pain than subjects in
the T group?
From here:
Case Six | Clinical Trial Sketch | Study of Tamoxifen and Raloxifene (STAR)
for the Prevention of Breast Cancer
The purpose of this study is
to examine the performance of the drug Raloxifene (relative to the drug Tamoxifen) in reducing the
incidence of breast cancer in postmenopausal women1 who are at increased risk of the disease2.
1. Postmenopausal women at increased risk for
developing invasive breast cancer, who meet one of the following criteria: At least 12 months since spontaneous menstrual
bleeding; Prior documented
hysterectomy and the surgical removal of fallopian tubes and ovaries; At least 55 years of age with prior
hysterectomy with or without surgical removal of the ovaries; Aged 35 to 54 years with a prior
hysterectomy without surgical removal of the ovaries or with a status of
ovaries unknown with documented follicle-stimulating hormone level
demonstrating elevation in postmenopausal range.
2. Women without prior breast cancer, but who are at
elevated risk for breast cancer: Histologically
confirmed lobular carcinoma in situ treated by local excision only or at least
1.66% probability of invasive breast cancer within 5 years using Breast Cancer
Risk Assessment Profile; No clinical
evidence of malignancy on physical exam within the past 180 days; No evidence of suspicious or malignant
disease on bilateral mammogram within the past year; No bilateral or unilateral prophylactic mastectomy and No prior invasive breast cancer or intraductal carcinoma in situ
Objectives: Determine whether Raloxifene is more or less effective than Tamoxifen in significantly reducing the incidence rate of invasive breast cancer in postmenopausal women; Evaluate the effects of Tamoxifen and Raloxifene on the incidence of intraductal carcinoma in situ, lobular carcinoma in situ, endometrial cancer, ischemic heart disease, fractures of the hip and spine, or Colles' fractures of the wrist in these participants; Evaluate the toxic effects of these regimens in these participants and Determine the effect of these regimens on the quality of life of these participants.
Sketch a comparative
clinical trial to evaluate the drug Raloxifene
(relative to the drug Tamoxifen)
in reducing the incidence of breast cancer in postmenopausal women1 who are at increased risk
of the disease2.
Solution
Purpose
of Treatment: The
purpose of this study is to examine the performance of the drug Raloxifene
(relative to the drug Tamoxifen)
in reducing the incidence of breast cancer in postmenopausal women1 who are at increased risk
of the disease2.
Eligible subjects
are: 1. postmenopausal women at increased risk for developing invasive breast
cancer, who meet one of the following criteria: At least 12 months since spontaneous
menstrual bleeding; Prior documented
hysterectomy and the surgical removal of fallopian tubes and ovaries; At least 55 years of age with prior
hysterectomy with or without surgical removal of the ovaries; Aged 35 to 54 years with a prior
hysterectomy without surgical removal of the ovaries or with a status of
ovaries unknown with documented follicle-stimulating hormone level
demonstrating elevation in postmenopausal range.
2. Women without prior breast cancer, but
who are at elevated risk for breast cancer: Histologically
confirmed lobular carcinoma in situ treated by local excision only or at least
1.66% probability of invasive breast cancer within 5 years using Breast Cancer
Risk Assessment Profile; No clinical
evidence of malignancy on physical exam within the past 180 days; No evidence of suspicious or malignant
disease on bilateral mammogram within the past year; No bilateral or unilateral prophylactic mastectomy and No prior invasive breast cancer or intraductal carcinoma in situ. The eligible
patients are briefed as to the details and potential risks and benefits of
study participation, and those who give informed consent and who meet
all inclusion and exclusion requirements are enrolled in the trial.
Study
treatments include Raloxifene and Tamoxifen.
Enrolled subjects are randomly assigned either to Raloxifene
with PlaceboTamoxifen or to Tamoxifen with PlaceboRalixifene.
Double-blinding is employed, so that neither the subjects
nor the clinical workers know the actual individual treatment
assignments.
Subjects are then followed for: Incidence of invasive breast cancer in postmenopausal women; Incidence of intraductal carcinoma in situ, Incidence of lobular carcinoma in situ, Incidence of endometrial cancer, Incidence of ischemic heart disease, Incidence of fractures of the hip and spine, and Incidence of Colles' fractures of the wrist, Toxic effects of the medications, and Quality of Life.
Case
Study - Gastric Adenocarcinoma
Case
Study - Myocardial Infarction
Case
Study - Traumatic Brain Injury
Case
Study - Carbon Monoxide Intoxication
Case Study - Ocular
Hypertension
From
http://clinicaltrials.gov: Study Phase
(FDA Clinical Trials)
Most clinical trials are designated as phase I, II, or
III, based on the type of questions that study is seeking to answer:
In Phase I clinical trials, researchers test a new drug or treatment in a small group
of people (20-80) for the first time to evaluate its safety, determine a safe
dosage range, and identify side effects.
In Phase II clinical trials, the study drug or treatment is given to a larger
group of people (100-300) to see if it is effective and to further evaluate its
safety.
In Phase III studies, the study drug or treatment is given to large groups of people
(1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to
commonly used treatments, and collect information that will allow the drug or
treatment to be used safely.
These phases are defined by the Food and Drug
Administration in the Code of Federal Regulations.
Comparative Clinical Trial
Advanced Stomach
Cancer (Gastric Adenocarcinoma)
Use of Combination Chemotherapy
The purpose of this trial is to test the combination
of Gleevec® (also known as imatinib
mesylate) and Taxotere (also known as docetaxel)
in patients with incurable stomach cancer. This study is being performed to see
if the combination of Gleevec and Taxotere
is an effective treatment for incurable stomach cancer with minimal side
effects.
Gleevec is a pill form of chemotherapy and is indicated for
the treatment of adult patients with chronic myeloid leukemia (CML) and
gastrointestinal stromal tumors (GIST). It is
considered experimental for the treatment of stomach cancer.
Taxotere is a chemotherapy which is injected into the vein. It
is approved for breast and lung cancer but has been shown to shrink many
different types of tumors. Taxotere has
been shown to shrink stomach cancer in about 20% - 30% of patients treated with
Taxotere.
An adenocarcinoma
is a cancer that develops in the glandular lining of an organ. A gastric adenocarcinoma is a cancer that that develops in the
glandular lining of the stomach.
Define advanced gastric adenocarcinoma for the purposes of this clinical trials
as surgically inoperable gastric adenocarcinoma.
This study is being performed to see if the
combination of Gleevec and Taxotere
is an effective treatment for advanced stomach cancer.
Sketch a comparative clinical trial for Gleevec+Taxotere versus Taxotere
in the treatment of advanced gastric adenocarcinoma.
Condition of Interest: advanced gastric adenocarcinoma,
defined as surgically
inoperable gastric adenocarcinoma.
Subjects: Adult patients diagnosed with advanced
gastric adenocarcinoma.
Recruitment and Informed Consent: We recruit volunteer candidates who have
been diagnosed with advanced gastric adenocarcinoma,
and who meet all requirements for study inclusion, We exclude all candidates
presenting one or more conditions for exclusion. The volunteers are briefed as
to the requirements, details, potential benefits and risk associated with trial
participation. Those who give informed consent agree to participate and are
enrolled in the trial.
Assignment to Treatment: Enrolled subjects are randomly assigned
to either Gleevec+Taxotere or to Placebo+Taxotere,
where Placebo represents a placebo version of Gleevec.
Double-blinding is employed in the trial, so that neither the study
subjects nor their clinical personnel know the actual assignment status of any
subject.
Endpoints and Follow-up: Subjects are followed for toxicity,
safety, effect and quality-of-life.
Toxicity involves severe events such as anaphylaxis
(shock), kidney or liver failure/damage, and the like.
Adverse Events involve lesser events like the things you
read in the package inserts: rashes, “dry mouth”, gastrointestinal effects,
nausea, and the like.
Effect involves the actual effect of the
treatment, measured as change in disease status or progression. In this case,
we’re dealing with progression and stage of the cancer: tumor size, metastasis
(spreading) and the like. We also consider survival time,vital
status and stomach function.
Quality of Life: We consider pain control, basic body
function, ability to work, live and play, ability to maintain cogent
consciousness, ability to live independently or with minimal assistance.
We compare the performance of each
treatment group in these results: Toxicity, Safety, Effect and QoL.
Comparative Clinical Trial
Magnesium
Sulfate versus Nimodipine
Determine the effectiveness of nimodipine versus magnesium sulfate in the prevention
of eclamptic seizures in patients with severe
pre-eclampsia.
Nimodipine: Patients receive nimodipine
by mouth every 4 hours. Treatment is continued until 24 hours post-partum.
Magnesium Sulfate: Patients receive a loading dose of magnesium
sulfate IV for 20 minutes, followed by continuous infusion of magnesium
sulfate. Treatment is continued until 24 hours post-partum.
Severe pre-eclampsia
involves the onset of hypertension
(high blood pressure) in the late stages of pregnancy, as well as proteinuria (excessive levels of protein
in the urine), thrombocytopenia
(deficiency of blood platelets) and swelling (edema).
This study is being performed to compare the
effectiveness of Magnesium Sulfate and Nimodipine in
the treatment of severe pre-eclampsia.
Sketch a comparative clinical trial for the
comparison of Magnesium Sulfate and Nimodipine in
the treatment of severe pre-eclampsia.
Condition of Interest: severe pre-eclampsia.
Subjects: Pregnant patients diagnosed with pre-eclampsia.
Recruitment and Informed Consent: We recruit volunteer candidates who have
been diagnosed with severe pre-eclampsia, and who
meet all requirements for study inclusion, We exclude all candidates presenting
one or more conditions for exclusion. The volunteers are briefed as to the
requirements, details, potential benefits and risk associated with trial
participation. Those who give informed consent agree to participate and are
enrolled in the trial.
Assignment to Treatment: Enrolled subjects are randomly assigned
to either magnesium sulfate + placebo
Endpoints and Follow-up: Subjects are followed for toxicity,
safety, effect and quality-of-life.
Toxicity involves severe events such as anaphylaxis
(shock), kidney or liver failure/damage, and the like.
Adverse Events involve lesser events like the things you
read in the package inserts: rashes, “dry mouth”, gastrointestinal effects,
nausea, and the like.
Effect involves the actual effect of the
treatment, measured as change in disease status or progression. In this case,
we’re dealing with the frequency and severity of eclamptic
seizures in the pregnant woman. We will also track the other aspects of
pre-eclampsia: hypertension (high blood pressure) in
the late stages of pregnancy, proteinuria (excessive
levels of protein in the urine), thrombocytopenia (deficiency of blood
platelets) and swelling (edema).
We compare the performance of each
treatment group in these results: Toxicity, Safety, Effect.
Basic Clinical Trial
Pre-eclampsia
Sildenafil Citrate
To determine the efficacy and safety of sildenafil citrate in the treatment of established
pre-eclampsia.
Sildenafil Citrate:
Better known as Viagra, this drug is a vaso-dilator.
The medication causes blood vessels to dilate, enabling a drop in blood pressure.
Pre-eclampsia involves the onset of hypertension (high blood
pressure) in the late stages of pregnancy, as well as proteinuria
(excessive levels of protein in the urine), thrombocytopenia (deficiency
of blood platelets) and swelling (edema).
This study is being performed to see if the Sildenafil Citrate is an effective treatment
for pre-eclampsia.
Sketch a basic clinical trial for Sildenafil Citrate in the treatment of Pre-eclampsia.
Condition of Interest: Pre-eclampsia.
Subjects: Pregnant patients diagnosed with pre-eclampsia.
Recruitment and Informed Consent: We recruit volunteer candidates who have
been diagnosed with pre-eclampsia, and who meet all
requirements for study inclusion, We exclude all candidates presenting one or
more conditions for exclusion. The volunteers are briefed as to the
requirements, details, potential benefits and risk associated with trial
participation. Those who give informed consent agree to participate and are
enrolled in the trial.
Assignment to Treatment: Enrolled subjects are randomly assigned
to either Sildenafil Citrate or to Placebo. Double-blinding
is employed in the trial, so that neither the study subjects nor their clinical
personnel know the actual assignment status of any subject.
Endpoints and Follow-up: Subjects are followed for toxicity,
safety, effect and quality-of-life.
Toxicity involves severe events such as anaphylaxis
(shock), kidney or liver failure/damage, and the like.
Adverse Events involve lesser events like the things you read
in the package inserts: rashes, “dry mouth”, gastrointestinal effects, nausea,
and the like.
Effect involves the actual effect of the
treatment, measured as change in disease status or progression. In this case,
we’re dealing equally with all aspects of pre-eclampsia.
We track the frequency and severity of eclamptic
seizures in the pregnant woman. We track all aspects of pre-eclampsia: hypertension (high blood pressure) in the late
stages of pregnancy, proteinuria (excessive levels of
protein in the urine), thrombocytopenia (deficiency of blood platelets) and
swelling (edema).
We compare the performance of each
treatment group in these results: Toxicity, Safety, Effect.
Old Case Studies
Case Study - Simvastatin and Heart Attacks
Heart Attacks
The heart
continuously pumps blood enriched with oxygen and vital nutrients through a
network of arteries to all parts of the body's tissues. The heart muscle itself
needs a plentiful supply of oxygen-rich blood, which is provided through a
network of coronary arteries. These arteries carry oxygen-rich blood to the
heart's muscular walls (the myocardium). Coronary artery disease is the most
common cause of heart attacks, which occurs when blood flow to the myocardium
is interrupted. Heart attack occurs when blood flow is blocked and tissue death
occurs from loss of oxygen, severely damaging the heart. Coronary artery
disease is the end result of a complex process commonly called "hardening
of the arteries"). This causes blockage of arteries and prevents
oxygen-rich blood from reaching the heart.
Cholesterol and Lipoproteins. The story begins with
cholesterol and sphere shaped bodies called lipoproteins that transport
cholesterol. Cholesterol is a white, powdery nutrient that is found in all
animal cells and in animal-based foods. The lipoproteins that transport
cholesterol are referred to by their size. The most commonly known are
low-density lipoproteins (LDL) and high density lipoproteins (HDL). In heart
disease, free radicals are released in artery linings and oxidize low-density
lipoproteins (LDL). The oxidized LDL is the basis for cholesterol build-up on
the artery walls. The injuries to the arteries during oxidation signal the
immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. These factors
initiate the inflammatory response. Macrophages literally "eat"
foreign debris, in this case oxidized LDL cholesterol. The process converts LDL
cholesterol into foamy cells that attach to the smooth muscle cells of the
arteries. The cholesterol becomes mushy and accumulates on artery walls. Over
time the cholesterol dries and forms a hard plaque, which causes further injury
to the walls of the arteries. Eventually these calcified (hardened) arteries
become narrower. As this narrowing and hardening process continues, blood flow
slows and prevents sufficient oxygen-rich blood from reaching the heart.
Simvastatin is a drug that interferes in the early stages of cholesterol.
This drug actively lowers the levels of serum cholesterol, and it is thought
that this effect may afford protection against heart attacks.
Sketch
a basic clinical trial of simvastatin that evaluates
the effectiveness of simvastatin in preventing heart
attacks.
Describe
the treatments, and the outcome(s) by which the treatments will be evaluated.
The
active treatment is simvastatin. A basic clinical
trial is indicated, so there will be a placebo version of simvastatin.
Do we
want a basic, or comparative trial ?
A
basic clinical trial, which uses a placebo for comparison.
Identify
the subject population for this trial.
For
the purpose of this trial, we might focus on subjects who are free of previous
heart attacks, but who do show elevated serum cholesterol. Subjects eligible
for the trial must volunteer and give informed consent in order to participate
in the trial.
Discuss
the assignment of subjects to the treatments in the trial.
Enrolled
subjects are randomly assigned to either simvastatin
or to its placebo version. Neither the subjects nor the clinical workers will
know which drug has been assigned – this is called double blinding.
We
will track the trial subjects in both treatment groups for a number of
outcomes:
Safety
– any adverse reactions to Taxol
Heart
Attack – do the subjects present heart attacks (MI) during follow-up?
Time
to Event – how long does it take the subjects to present MI?
Survival
Status – do the subjects die during followup? Do they
die of MI?
Cholesterol
Levels – do subjects show decreased serum cholesterol?
Case Study - Corticosteroids
and Traumatic Brain Injury (TBI)
Traumatic Brain
Injury
Traumatic Brain
Injury (TBI) involves the injury of the brain when it involves sudden or
intense physical force resulting in the presence of Concussion, Skull Fracture,
or Bleeding and Tissue Damage (Contusions, Lacerations, Hemorrhaging) involving
the brain. Tissue damage to the brain results from the traumatic force of
injury, swelling (inflammation) and bleeding. Consequences of TBI include
death, intellectual impairment, social and emotional impairment and physical
disability.
Inflammation
Inflammation is the
response of living tissue to damage. The acute inflammatory response has 3 main
functions. The affected area is occupied by a transient material called the
acute inflammatory exudate. The exudate
carries proteins, fluid and cells from local blood vessels into the damaged
area to mediate local defenses. The damaged tissue can be broken down and
partially liquefied, and the debris removed from the site of damage.
The cause of acute
inflammation may be due to physical damage, chemical substances,
micro-organisms or other agents. The inflammatory response consist of changes
in blood flow, increased permeability of blood vessels and escape of cells from
the blood into the tissues. The changes are essentially the same whatever the
cause and wherever the site.
Acute inflammation
is short-lasting, lasting only a few days. If it is longer lasting however,
then it is referred to as chronic inflammation.
Corticosteroids
Corticosteroids are
drugs that reduce inflammation. Corticosteroids, often referred to as steroids,
are related to cortisol, a naturally produced hormone
that controls many important body functions. In normal amounts, corticosteroids
play an important role in the regulation of blood sugar levels, salt and water,
and in metabolism and growth. They also reduce the activity of the body's
immune system and act to suppress allergic reactions. Corticosteroids are used
to decrease the inflammation that causes the pain, redness and swelling
associated with inflammatory diseases.
Sketch
a basic clinical trial of corticosteroids that evaluates the effectiveness of
corticosteroids in reducing death and disability following TBI.
Describe
the treatments, and the outcome(s) by which the treatments will be evaluated.
The
active treatment is corticosteroid (CS). A basic clinical trial is indicated,
so there will be a placebo version of CS.
Do we
want a basic, or comparative trial ?
A
basic clinical trial, which uses a placebo for comparison.
Identify
the subject population for this trial.
Subjects
who qualify for this trial have just suffered a traumatic brain injury (TBI).
Subjects eligible for the trial must volunteer and give informed consent in
order to participate in the trial. Given the altered consciousness that goes
with brain injuries, this trial will utilize the appropriate proxy consent,
in which the subject’s medical agent gives consent.
Discuss
the assignment of subjects to the treatments in the trial.
Enrolled
subjects are randomly assigned to either CS or to its placebo version. Neither
the subjects nor the clinical workers will know which drug has been assigned –
this is called double blinding.
We
will track the trial subjects in both treatment groups for a number of
outcomes:
Safety
– any adverse reactions to corticosteroid (CS)?
Physical
Effects – how does post treatment brain tissue damage compare?
Cognitive
Effects – how well does the patient recover cognitive function:
Memory Function
Coordination
Speech
Thought
Emotional Stability
Impulse Control
Life
Effects – how well does the patient recover life function:
Career/Job Function
Social Function
Family Function
Psycho/Sexual Function
Mortality
– how do death rates compare for each treatment group?
Case Study -
Acute Carbon Monoxide Intoxication
Normal Oxygen
versus Normal Oxygen + Hyperbaric Oxygen
Carbon Monoxide
and Hemoglobin
Hemoglobin is a protein that is carried by red cells. Heme is the prosthetic group that mediates
reversible binding of oxygen by hemoglobin. This mechanism allows the red blood
cells to transport oxygen to the cells of the body. Globin
is the protein that surrounds and protects the heme
molecule. It picks up oxygen in the lungs and delivers it to the peripheral
tissues to maintain the viability of cells. Carbon monoxide quickly
binds with hemoglobin with an affinity 200 to 250 times greater than that of oxygen.
The resulting bonding of carbon monoxide and hemoglobin is called carboxyhemoglobin (COHb).
Effects of Carbon
Monoxide Intoxication
Carbon monoxide
inhibits the blood's ability to carry oxygen to body tissues including vital organs
such as the heart and brain. When CO is inhaled, it combines with the oxygen
carrying hemoglobin of the blood to form carboxyhemoglobin.
Once combined with the hemoglobin, that hemoglobin is no longer available for
transporting oxygen.
Symptoms of carbon
monoxide intoxication vary with the degree of intoxication, and the nature of
damage caused to affected organs. For the purposes of this trial, let us focus
on the neurological aspects: Cognitive Skills, Memory Impairment, Coordination,
Headaches.
Normal Oxygen
Therapy
A nonrebreather mask supplies 100% oxygen at the usual
atmospheric pressure to quickly clear COHb from the
blood. This frees up the hemoglobin for oxygen uptake and transport.
Hyperbaric Oxygen
Hyperbaric oxygen
involves delivering oxygen to a patient under higher levels of atmospheric
pressure. Once a patient with acute carbon monoxide poisoning has received
initial treatment and is in stable condition, the physician must decide whether
to initiate hyperbaric oxygen therapy. Hyperbaric oxygen may allow more rapid
clearance of COHb.
Sketch a
comparative clinical trial of normal versus enhanced oxygen therapies in the
treatment of acute carbon monoxide intoxication.
Describe
the treatments, and the outcome(s) by which the treatments will be evaluated.
The
standard treatment is oxygen therapy (OT). The experimental treatment is OT
followed by hyper-baric oxygen therapy (OT+HOT).
Do we
want a basic, or comparative trial ?
A comparative
clinical trial, which compares the oxygen treatments.
Identify
the subject population for this trial.
Subjects
who qualify for this trial have just suffered acute carbon monoxide
intoxication. Subjects eligible for the trial must volunteer and give informed
consent in order to participate in the trial. Given the altered consciousness
that goes with brain injuries, this trial may utilize both direct consent and proxy
consent, in which the subject’s medical agent gives consent, depending on
the state of the subject.
Discuss
the assignment of subjects to the treatments in the trial.
Enrolled
subjects are randomly assigned to either OT or to OT+HOT. Neither the subjects
nor the clinical workers will know which drug has been assigned – this is
called double blinding.
We
will track the trial subjects in both treatment groups for a number of
outcomes:
Safety
– any adverse reactions to either treatment?
Physical
Effects – how does post treatment brain tissue damage compare?
Cognitive
Effects – how well does the patient recover cognitive function:
Memory Function
Coordination
Speech
Thought
Emotional Stability
Impulse Control
Physical
Effects – how often do patients persist in certain effects after treatment?
Headaches
Balance/Coordination
Mortality – how do
death rates compare for each treatment group?
Case Study - Nephrogenic Diabetes
Insipidus
Nephrogenic Diabetes Insipidus is a disease in which the patient’s kidneys are
resistant to the diuretic hormone vasopressin. Vasopressin is a hormone
produced by the hypothalamus, and among other things, stimulates the kidneys to
preserve water and concentrate urine. In NDI, the kidneys are not responsive to
normal amounts of vasopressin.
Symptoms of NDI
include:
Excessive Thirst – polydipsia
Excessive and Dilute
Urine – polyuria
Complications
of NDI include:
Acute Hyperosmolar Dehydration – excessively high blood plasma
concetration
Low
Blood Pressure – hypotension
Shock
Poor
Nutrition and Growth
In
NDI, the problem isn’t a lack of vasopressin, it is a lack of response to
vasopressin. Suppose that we have a new treatment for NDI cases who have normal
levels of vasopressin, but whose kidneys do not respond adequately to the
vasopressin – let’s call it ActiVasex. The purpose of ActiVasex
is to enable the kidneys to respond to the body’s levels of vasopressin.
Suppose further that the only effective intervention for cases of NDI is that
of hydration – maintaining a steady supply of water to replace the outgoing
urine. Assume that all subjects will continue to drink as much water as they
need, regardless of treatment group.
Sketch a basic
clinical trial that evaluates the
experimental treatment ActiVasex in the
treatment of NDI cases, following the examples from class and in the course
files. For full credit, discuss completely.
Solution:
Population
of Interest: Cases of Nephrogenic Diabetes Insipidus;
Treatments:
ActiVasex, and Placebo* ;
We
begin with a set of possible subjects for our study. Those who present with NDI
are briefed as to the particulars of the study, including information about the
possible treatments to be assigned, the methods of assigning treatments and the
potential risks and benefits of the treatments. Those who give informed
consent and join the trial are then randomly assigned to
either Activasex or to Placebo.
Neither the assigned subjects nor their clinical workers are aware of the
treatment assignments (double blinding).
The
subjects are then tracked for the following:
Degree of Thirst
Frequency
of Urination
Concentration
of Urine
Acute Hyperosmolar Dehydration – excessively high blood plasma
concentration
Low Blood
Pressure – hypotension
Shock
Poor
Nutrition and Growth
Medication
Toxicity or Allergic Reactions
We
also track the occurrence of side effects and toxicity.
Case
Study - Ocular Hypertension / Early Prevention of Glaucoma
The eye
is filled with a fluid – there are mechanisms, which provide for the
replacement and draining of this fluid. There is a certain amount of intra-ocular
pressure exerted by the fluid in the eye. A condition called ocular
hypertension (OHT) involves excessive pressures exerted by the
fluid in the eye – sustained OHT can cause damage to the optic nerve, which can
then cause the onset of glaucoma. Glaucoma involves loss of
visual acuity and visual fields due to optic nerve damage. These losses include
loss of visual acuity and loss of peripheral vision.
It is thought that
individuals with OHT are at high risk of developing glaucoma. The purpose of
this clinical trial is the early prevention of glaucoma in individuals who are
glaucoma-free but exhibit ocular hypertension. There is a standard suite of
medications that are used in treating OHT in glaucoma patients. The purpose
of this trial is the evaluation of this suite of medications in the early
prevention of glaucoma.
Sketch a basic
clinical trial that evaluates the
standard OHT suite in the early prevention of glaucoma in OHT subjects,
following the examples from class and in the course files. For full credit,
discuss completely.
Solution:
The
treatments:
Placebo/Close
Observation –
Placebo version of standard OHT medication suite. Watch these subjects for
progression of OHT and Glaucoma.
Standard
Suite of Glaucoma/OHT Drugs – The usual suite of meds given to glaucoma patients in
reducing intra-ocular hypertension.
Primary
Outcome to be observed is the progression of glaucoma from OHT. The basic
issues are whether the OHT case progresses to Glaucoma, and the extent to which
the onset of Glaucoma is delayed.
Secondary
Outcomes to be observed are Adverse Events and Toxicity
We
require individuals who are currently free of Glaucoma, but who exhibit
excessive intra-ocular pressure – Ocular Hypertension (OHT).
Subjects
who meet all requirements for study admission and who give informed consent are
then randomly assigned to either Placebo/Observation or Standard
Glaucoma/OHT Suite. Double blinding is employed – neither the subjects nor
the clinical workers know the treatment status of the subjects.
We also
track the occurrence of side effects and toxicity.
Case
Study - Nephrogenic Diabetes Insipidus
Nephrogenic Diabetes Insipidus is a disease in which the patient’s kidneys are
resistant to the diuretic hormone vasopressin. Vasopressin is a hormone
produced by the hypothalamus, and among other things, stimulates the kidneys to
preserve water and concentrate urine. In NDI, the kidneys are not responsive to
normal amounts of vasopressin.
Symptoms of NDI include:
Excessive Thirst – polydipsia
Excessive and Dilute
Urine – polyuria
Complications
of NDI include:
Acute
Hyperosmolar Dehydration – excessively high blood
plasma concetration
Low
Blood Pressure – hypotension
Shock
Poor
Nutrition and Growth
In
NDI, the problem isn’t a lack of vasopressin, it is a lack of response to
vasopressin. Suppose that we have a new treatment for NDI cases who have normal
levels of vasopressin, but whose kidneys do not respond adequately to the
vasopressin – let’s call it ActiVasex. The purpose of ActiVasex is to enable the kidneys to respond to the
body’s levels of vasopressin. Suppose further that the only effective
intervention for cases of NDI is that of hydration – maintaining a steady
supply of water to replace the outgoing urine. Assume that all subjects will
continue to drink as much water as they need, regardless of treatment group.
Sketch a basic
clinical trial that evaluates the
experimental treatment ActiVasex in the
treatment of NDI cases, following the examples from class and in the course
files. For full credit, discuss completely.
Solution:
Population
of Interest: Cases of Nephrogenic Diabetes Insipidus;
Treatments:
ActiVasex, and Placebo* ;
We
begin with a set of possible subjects for our study. Those who present with NDI
are briefed as to the particulars of the study, including information about the
possible treatments to be assigned, the methods of assigning treatments and the
potential risks and benefits of the treatments. Those who give informed
consent and join the trial are then randomly assigned to
either Activasex or to Placebo.
Neither the assigned subjects nor their clinical workers are aware of the
treatment assignments (double blinding).
The
subjects are then tracked for the following:
Degree
of Thirst
Frequency
of Urination
Concentration
of Urine
Acute Hyperosmolar Dehydration – excessively high blood plasma
concentration
Low Blood
Pressure – hypotension
Shock
Poor
Nutrition and Growth
Medication
Toxicity or Allergic Reactions
We
also track the occurrence of side effects and toxicity.
Clinical Trial Design Fault
Spot
Case
Study: Clinical Trial Design Fault Spot
We have
sketched complete designs. We will now critique partial designs.
In this
case study, each part describes a clinical trial design set-up. Indicate the
problem(s) with the approach(es) used in each part.
A large
scale AIDS clinical trial is conducted in
a Third World nation, in which the effects of a cheap, low-dose regimen of AZT(Zidovudine) in pregnant women is compared to the effects of
a placebo in pregnant women. Randomization and Double Blinding is employed. The
intended effect to be evaluated is the prevention of HIV infection in the child
carried by the HIV infected mother.
CDC/WHO
actually conducted a trial of this type - the primary objection was the use of
a placebo in subjects with AIDS. The defense provided by the principles in this
study were:
Conventional
AIDS therapies are simply not available to AIDS patients in the 3rd
world countries involved.
The actual
subjects in the study were the developing children - they might be at risk at
higher doses of AZT and the intended purpose of the AZT is the prevention of
HIV transmission to these developing children.
In a
comparative clinical trial, a new
surgical method is compared to a standard surgical method. Study physicians
classify subjects by the severity of their disease, and assign only the
"mild" or "moderate" subjects to the new surgical method.
Only the "severe" subjects are assigned to the standard surgical
method.
The
subjects should be randomly assigned to treatment groups. Under this study,
subjects in each treatment group differ by treatment type and by severity. So
we wouldn't know whether to attribute difference in outcome to treatment type,
severity, or a combination of both treatment and severity.
Suppose a
clinical trial is used to evaluate the
safety of Drug X. The trial uses adult volunteers. The researchers claim that
this trial is sufficient to ensure the safety of Drug X for pregnant women and
children.
Data from
men cannot automatically be applied to women (pregnant or otherwise) and
children.
DES(Diethylstibestol) is an artificial hormone, whose intended effect is the prevention of
Spontaneous Abortion in pregnant women. Spontaneous Abortion is a special type
of miscarriage, not due to external factors such as injury. A trial is
conducted in which two volunteer groups are recruited, one set of volunteers is
recruited to try DES, the other group is recruited solely for observation(no
treatment). The DES group knows it is getting DES, and the observation group
receives no treatment. The physicians and nurse know which women are getting
DES, and which are receiving no treatment.
Subjects
should be assigned randomly to either DES or Placebo. Double blinding should be
employed. Otherwise, differences in outcome might not be due to DES.
The
groups that are recruited specifically for each treatment might well differ in
important ways.
Disease X
Therapeutic Trial
Disease X is a
disease which is caused by an infection. It usually takes five (5) years for
disease X to present symptoms. Left untreated, disease X produces severe and
occasionally fatal symptoms and complications. Suppose that an effective,
standard treatment, oldtreatX, is available. Suppose
further that a new treatment, ihopeitworksX is
available for evaluation. A basic clinical trial is
proposed.
Use of
placebo here is inappropriate.
Disease Y
Preventive Trial
Consider disease Y,
which is caused by a bacterial infection, primarily affects children and which
produces severe and occasionally fatal complications. Suppose that a candidate
vaccine, newvaxY, is available for evaluation. A
randomized, double-blinded basic clinical trial for newvaxY
is proposed. This trial will use adult subjects only.
A
pediatric (child-focused) trial is required here to establish the safety and
effectiveness of the new vaccine.
The basic
trial is unethical, since an effective vaccine is available, and the
consequences of disease Y are potentially nasty.
Cancer Z
Prevention Trial
Suppose cancer Z
typically strikes adults who are aged 40-65 years, and suppose further that no
established preventive treatment is available. Suppose that a new treatment, preventZ, which is intended to help prevent cancer Z is
available for evaluation. A basic clinical trial is proposed. The trial will
focus on adult subjects aged 25-30 years, who have no prior history of cancer
Z. Study subjects will be followed for five (5) years after study entry. The
trial will be a double-blinded, randomized basic clinical trial.
The
follow-up time (5 years) is inadequate.
Sample Survey Design Hypermedia Resources
http://www.pbs.org/fmc/segments/progseg7.htm
http://www.public.iastate.edu/~jhutter/406/lectureoutline.doc
http://www.csudh.edu/dearhabermas/sampling01.htm
http://www.bartleby.com/65/po/poll.html
http://www.stat.ucla.edu/~rgould/m12s01/survey.pdf
http://fly.hiwaay.net/~jmcmulle/450polls.htm
Pew Center
Links
http://people-press.org/reports/
http://people-press.org/reports/display.php3?ReportID=12
http://people-press.org/reports/display.php3?ReportID=89
About Sample Surveys
Our brief overview of sample survey methodology
focuses on what is sometimes called “scientific polling.” This type of survey
design relies on a few well-defined features: use of a random sampling scheme,
use of a carefully-designed survey instrument and on carefully-planned
interviewing techniques.
There are a few key concepts in a well-designed sample
survey, each keyed to simple question or questions.
Why? – Why are you conducting the survey? Is this
a brief poll? Is this a detailed survey of a population? Are you predicting,
describing, or both?
What? –What do you want to learn?
Who? – Consider the population of interest. Who
exactly will you sample?
How? – How do you obtain your random sample of
respondent candidates? How do you design your survey instrument? How do you
deliver the instrument/conduct the interview?
When? – What is the time-frame for your survey? Is
this a short-term project, or an ongoing activity? What is your time-line from
beginning to publication?
Sample Survey Process
Define Population(Pop)
Acquire Sampling Frame within Population(Frame Pop)
Design Random Sampling Process(RSP)
Select Random Sample of Candidate Respondents Using
RSP from Frame Pop
Design Survey Interview Instrument and Interview
Protocol (IIP)
Interview Consenting Respondents using IIP
Compile, Analyze and Report Findings
The 1936 and 1948 Presidential Polls
A number of important survey failures stressed the
need for Random Sampling.The Literary Digest US
Presidential Poll of 1936 used a non-random sample targeting telephone
directories, automobile registries and the LD subscriber list. Even though 2.4
million respondents were acquired for the poll, the poll failed miserably.
Moreover, the bulk of US voters in the 1936 Presidential Election were
neither automobile owners nor telephone owners nor LD subscribers.
1936: Alf Landon
(Incumbent Governor Kansas (R), father of Nancy Kassebaum ) versus Franklin
Delano Roosevelt (Incumbent President (D), previously Governor New
York (D) )
Links for the 1936 LD Poll: 1, 2, 3
Three major polling organizations - Crossley, Roper and Gallup, suffered poll
failures for the 1948 US Presidential Election. All three organizations drew
non-random samples which nicely resembled the population of US Voters, and all
three polls still failed, though by a small margin. The problem was with the
use of quota sampling.In
quota sampling, poll workers are free to use judgment in selecting respondents,
so long as the selected respondents meet quota requirements.
Gallup did two random-sample based polls for the 1936
US Presidential Election - both samples were much smaller than the 2.4 million LD
Poll Sample. Gallup’s 1936 polls correctly predicted both the results of
the Literary Digest Poll and the Actual 1936 US Presidential Election
Results. The bizarre thing is that the Gallup people did not use Random
Sampling in the 1948 US Presidential Election Poll.
1948: Thomas Dewey(Incumbent
Governor New York) versus Truman (Incumbent
President (D)
Links for the 1948 Presidential Polls: 1, 2, 3
After the 1948 Presidential Poll failures, the
importance of random sampling became clear.
Supplemental Sample
Survey Notes
glossary gives
a glossary of terms used in Sample Survey Designs.
Sample Survey Design Faults
Sample Survey Design Fault Spot
Case
Study: Clinical Trial Design Fault Spot
We have sketched
complete designs. We will now critique partial designs.
In this
case study, each part describes a clinical trial design set-up. Indicate the
problem(s) with the approach(es) used in each part.
A large
scale AIDS clinical trial is conducted in
a Third World nation, in which the effects of a cheap, low-dose regimen of AZT(Zidovudine) in pregnant women is compared to the effects of
a placebo in pregnant women. Randomization and Double Blinding is employed. The
intended effect to be evaluated is the prevention of HIV infection in the child
carried by the HIV infected mother.
CDC/WHO
actually conducted a trial of this type - the primary objection was the use of
a placebo in subjects with AIDS. The defense provided by the principles in this
study were:
Conventional
AIDS therapies are simply not available to AIDS patients in the 3rd
world countries involved.
The
actual subjects in the study were the developing children - they might be at
risk at higher doses of AZT and the intended purpose of the AZT is the
prevention of HIV transmission to these developing children.
In a
comparative clinical trial, a new
surgical method is compared to a standard surgical method. Study physicians
classify subjects by the severity of their disease, and assign only the
"mild" or "moderate" subjects to the new surgical method.
Only the "severe" subjects are assigned to the standard surgical
method.
The
subjects should be randomly assigned to treatment groups. Under this study,
subjects in each treatment group differ by treatment type and by severity. So
we wouldn't know whether to attribute difference in outcome to treatment type,
severity, or a combination of both treatment and severity.
Suppose a
clinical trial is used to evaluate the
safety of Drug X. The trial uses adult volunteers. The researchers claim that
this trial is sufficient to ensure the safety of Drug X for pregnant women and
children.
Data from
men cannot automatically be applied to women (pregnant or otherwise) and
children.
DES(Diethylstibestol) is an artificial hormone, whose intended effect is the prevention of
Spontaneous Abortion in pregnant women. Spontaneous Abortion is a special type
of miscarriage, not due to external factors such as injury. A trial is
conducted in which two volunteer groups are recruited, one set of volunteers is
recruited to try DES, the other group is recruited solely for observation(no
treatment). The DES group knows it is getting DES, and the observation group
receives no treatment. The physicians and nurse know which women are getting
DES, and which are receiving no treatment.
Subjects
should be assigned randomly to either DES or Placebo. Double blinding should be
employed. Otherwise, differences in outcome might not be due to DES.
The
groups that are recruited specifically for each treatment might well differ in
important ways.
Disease X
Therapeutic Trial
Disease X is a
disease which is caused by an infection. It usually takes five (5) years for
disease X to present symptoms. Left untreated, disease X produces severe and
occasionally fatal symptoms and complications. Suppose that an effective,
standard treatment, oldtreatX, is available. Suppose
further that a new treatment, ihopeitworksX is
available for evaluation. A basic clinical trial is
proposed.
Use of placebo
here is inappropriate.
Disease Y
Preventive Trial
Consider disease Y,
which is caused by a bacterial infection, primarily affects children and which
produces severe and occasionally fatal complications. Suppose that a candidate
vaccine, newvaxY, is available for evaluation. A
randomized, double-blinded basic clinical trial for newvaxY
is proposed. This trial will use adult subjects only.
A
pediatric (child-focused) trial is required here to establish the safety and
effectiveness of the new vaccine.
The basic
trial is unethical, since an effective vaccine is available, and the
consequences of disease Y are potentially nasty.
Cancer Z
Prevention Trial
Suppose cancer Z
typically strikes adults who are aged 40-65 years, and suppose further that no
established preventive treatment is available. Suppose that a new treatment, preventZ, which is intended to help prevent cancer Z is
available for evaluation. A basic clinical trial is proposed. The trial will
focus on adult subjects aged 25-30 years, who have no prior history of cancer
Z. Study subjects will be followed for five (5) years after study entry. The
trial will be a double-blinded, randomized basic clinical trial.
The
follow-up time (5 years) is inadequate.
Sample Survey Design Hypermedia Resources
http://www.pbs.org/fmc/segments/progseg7.htm
http://www.public.iastate.edu/~jhutter/406/lectureoutline.doc
http://www.csudh.edu/dearhabermas/sampling01.htm
http://www.bartleby.com/65/po/poll.html
http://www.stat.ucla.edu/~rgould/m12s01/survey.pdf
http://fly.hiwaay.net/~jmcmulle/450polls.htm
Pew Center
Links
http://people-press.org/reports/
http://people-press.org/reports/display.php3?ReportID=12
http://people-press.org/reports/display.php3?ReportID=89
About Sample Surveys
Our brief overview of sample survey methodology
focuses on what is sometimes called “scientific polling.” This type of survey
design relies on a few well-defined features: use of a random sampling scheme,
use of a carefully-designed survey instrument and on carefully-planned
interviewing techniques.
There are a few key concepts in a well-designed sample
survey, each keyed to simple question or questions.
Why? – Why are you conducting the survey? Is
this a brief poll? Is this a detailed survey of a population? Are you
predicting, describing, or both?
What? –What do you want to learn?
Who? – Consider the population of interest. Who exactly
will you sample?
How? – How do you obtain your random sample of
respondent candidates? How do you design your survey instrument? How do you
deliver the instrument/conduct the interview?
When? – What is the time-frame for your survey? Is
this a short-term project, or an ongoing activity? What is your time-line from
beginning to publication?
Sample Survey Process
Define Population(Pop)
Acquire Sampling Frame within Population(Frame Pop)
Design Random Sampling Process(RSP)
Select Random Sample of Candidate Respondents Using
RSP from Frame Pop
Design Survey Interview Instrument and Interview
Protocol (IIP)
Interview Consenting Respondents using IIP
Compile, Analyze and Report Findings
The 1936 and 1948 Presidential Polls
A number of important survey failures stressed the
need for Random Sampling.The Literary Digest US
Presidential Poll of 1936 used a non-random sample targeting telephone
directories, automobile registries and the LD subscriber list. Even though 2.4
million respondents were acquired for the poll, the poll failed miserably.
Moreover, the bulk of US voters in the 1936 Presidential Election were
neither automobile owners nor telephone owners nor LD subscribers.
1936: Alf Landon
(Incumbent Governor Kansas (R), father of Nancy Kassebaum ) versus Franklin
Delano Roosevelt (Incumbent President (D), previously Governor New
York (D) )
Links for the 1936 LD Poll: 1, 2, 3
Three major polling organizations - Crossley, Roper and Gallup, suffered poll
failures for the 1948 US Presidential Election. All three organizations drew
non-random samples which nicely resembled the population of US Voters, and all
three polls still failed, though by a small margin. The problem was with the
use of quota sampling.In
quota sampling, poll workers are free to use judgment in selecting respondents,
so long as the selected respondents meet quota requirements.
Gallup did two random-sample based polls for the 1936
US Presidential Election - both samples were much smaller than the 2.4 million LD
Poll Sample. Gallup’s 1936 polls correctly predicted both the results of
the Literary Digest Poll and the Actual 1936 US Presidential Election
Results. The bizarre thing is that the Gallup people did not use Random
Sampling in the 1948 US Presidential Election Poll.
1948: Thomas Dewey(Incumbent
Governor New York) versus Truman (Incumbent
President (D)
Links for the 1948 Presidential Polls: 1, 2, 3
After the 1948 Presidential Poll failures, the
importance of random sampling became clear.
Supplemental Sample
Survey Notes
glossary gives
a glossary of terms used in Sample Survey Designs.
Sample Survey Design Faults
Sample Survey Design Fault Spot
We have sketched complete designs. We will
now critique partial designs.
In this case study, each part describes a
sample survey design set-up. Indicate the problem(s) with the approach(es) used in each part.
The Communications Department of a University conducts a survey of its major
students(prior to graduation) regarding their satisfaction levels with their
degree program. Random sampling is employed, and the survey instrument is
unbiased and properly written. The respondents are interviewed face-to-face by
department faculty members.
Problems Include:
The face-to-face thing needs to go - you'll
get hopelessly biased responses based on the perceived expectations of the
faculty {modified Hawthorne Effect}.
A sample survey design targets membership lists of US churches, and surveys a random
sample of members regarding attitudes toward god and religion. The survey
people then claim that their results apply to the general US population.
Problems Include:
The US genpop
cannot be captured by the specified list of church rolls - not even if this
list magically included every single body of followers of every organised religion in the US.
In 1987, Shere
Hite published Women and Love. The
author distributed 100,000 questionnaires through various women's groups , asking
questions about love, sex and relations between women and men. Of all the
questionnaires distributed, 4.5% were returned. Hite based her findings based
on these returned surveys. Her gist was that her results represented a general
female population.
Problems Include:
The femgenpop
cannot be captured by women's group rosters - even every single women's group
is included.
The response rate (4.5%) is simply too
inadequate - there may be a difference in opinions between those who responded
and those who did not.
A survey regarding the treatment of interned Japanese-Americans is conducted sometime
during 1941-1945. The surveyed population is the population of interned
Japanese-Americans, and is conducted by uniformed US Army personnel. A random
sample is selected for the survey. Assume that the sample survey instrument is
worded properly.
Problems Include:
This one is hopelessly hopeless.
The use of US military personnel is likely
to ellicit biased responses from the internees.
The basic status of the respondents
(prisoners) may prevent meaningful responses from emerging.
Euthanasia / Assisted Suicide Survey
The term euthanasia loosely refers to a variety of
procedures in which a patient's life is actively or passively ended, or in
which the patient is assisted in dying. Suppose a sample survey design attempts
to determine US attitudes towards euthanasia. This design will use a national
(US) random sample of adults who have had a relative die of a terminal illness,
or who have a relative dying of a terminal illness. The respondents will be
interviewed by a specially trained health professional. The designers hope that
the results will reflect general US attitudes regarding
euthanasia.
Problems Include:
Euthanasia is a sensitive topic, and the topic
itself may cause bias in the responses.
The general opinion may differ
systematically from the opinions held by people close to the topic - people
close to the topic may have more extreme opinions (pro and con) than the genpop.
The sampling cannot represent the genpop.
Political Candidate Preference / Voting
Survey
Suppose that a sample survey design is desired which
will predict the outcome of a particular election. An election usually involves
the selection of a candidate (or candidates) for a particular office (or
offices). An election might also involve referenda, in which voters decide a
particular question. The design uses a random sample of likely voters (adults
who are registered to vote, or intend to register to vote, and intend to vote),
and is conducted 3 weeks prior to the election.
Problems Include:
3 weeks is potentially a looooooong time in political science.
We might want to "tighten up" the
definition of "likely voter" to include only registered voters who
report themselves likely to vote.