Session 1.5
Summaries
15th June 2009
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 - Therapeutic 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 treat AIDS cases by interfering with the ability of HIV to function or reproduce. Consider the description of clinical trials evaluating such a vaccine, say TheraVaxHIVtm.
Case Description: Sketch out a clinical trial design for TheraVaxHIVtm.
Case Objectives:
Describe the treatments, and the outcome(s) by which the treatments will be evaluated.
Do we want a basic, or comparative trial ?
Identify the subject population for this trial.
Discuss the assignment of subjects to the treatments in the trial.
TheraVaxHIV is designed to treat individuals infected by HIV.
Since the purpose of TheraVaxHIV is to treat AIDS, we might pursue two designs:
Vaccines Only
We'll need a standard, proven version of a therapeutic vaccine for HIV, say Standard VAX.
Individuals who are infected with HIV comprise the subject population.
Individuals who are confirmed HIV+ infection are eligible for this study. Usually, an adult population is used. Separate provisions are generally required for children (pediatric trials).
Individuals who are eligible for study inclusion are briefed
as to the benefits and risks of participation in the trial. Those who understand these risks and benefits and wish to participate then give informed consent, and are enrolled.
Enrolled subjects are then randomly assigned to either TheraVaxHIV or Standard VAX. These subjects are then tracked over time for HIV infection status, survival, complications, quality of life, side effects and vaccine toxicity.
Combination Therapy
We'll need the standard, proven non-vaccine therapy for HIV, say Standard HIV
Individuals who are infected with HIV comprise the subject population.
Individuals who are confirmed HIV+ infection are eligible for this study. Usually, an adult population is used. Separate provisions are generally required for children (pediatric trials).
Individuals who are eligible for study inclusion are briefed
as to the benefits and risks of participation in the trial. Those who understand these risks and benefits and wish to participate then give informed consent, and are enrolled.
Enrolled subjects are
then randomly assigned to either
Case Study - Pick's Disease
Definition
Pick's disease is a form of dementia characterized by a slowly progressive deterioration of social skills and changes in personality, along with impairment of intellect, memory, and language. Although the disease usually affects individuals between the ages of 40 and 60, the age of onset may range from 20 to 80. Patients typically have atrophy of the frontal and temporal lobes of the brain. Some nerve cells have characteristic abnormalities when viewed under a microscope. The cause of the disease is unknown.
Symptoms
Although the disease varies greatly in the way it affects individuals, there is a common core of symptoms among patients, which may be present at different stages of the disease. These symptoms include loss of memory, lack of spontaneity, difficulty in thinking or concentrating, and disturbances of speech. Other symptoms include gradual emotional dullness, loss of moral judgment, and progressive dementia.
Treatment
There is no cure or specific treatment for Pick's disease. Its progression cannot be slowed. However, some of the symptoms of the disease may be treated effectively.
Progression
The course of Pick's disease is an inevitable progressive deterioration. The length of progression varies, ranging from less than 2 years in some to more than 10 years in others. Death is usually caused by infection.
Basic Clinical Trial
Consider the fictitious medication Recovex, which is designed to treat Pick’s Disease. Sketch a basic clinical trial for the use of Recovex in treating people with Pick’s Disease.
Learn More about Pick’s Disease:
http://www.zarcrom.com/users/alzheimers/odem/pk5a.html
http://www.ninds.nih.gov/health_and_medical/disorders/picks_doc.htm
http://dementia.ion.ucl.ac.uk/candid/factsheets/facts1.htm
http://www.emedicine.com/NEURO/topic311.htm
Solution:
The treatments:
Placebo – Watch these subjects for symptoms and progression of Pick's Disease.
Recovex – Watch these subjects for reduced symptoms and slower progression of Pick's Disease (relative to placebo).
Primary Symptoms to be tracked include: loss of memory, lack of spontaneity, difficulty in thinking or concentrating, and disturbances of speech. Other symptoms include gradual emotional dullness, loss of moral judgment, and progressive dementia.
Secondary Outcomes to be observed are Adverse Events and Toxicity
We require individuals who are diagnosed with Pick's Disease.
Subjects who meet all requirements for study admission and who give informed consent (either directly or by appropriate proxy). are then randomly assigned to either Placebo or to Recovex. Double blinding is employed – neither the subjects nor the clinical workers know the treatment status of the subjects.
Case Study: Herceptin
In the natural course of breast cancer, a critical event is metastasis - the spread of malignant cells beyond the source organ. Herceptin is a candidate treatment for advanced cases of breast cancer.
Details:
In 25-30% of breast cancer cases, the protein HER2/neu is over-expressed. HER2/neu serves as a growth signal receiver for breast cancer cells. The intended effect of herceptin is to block this receptor. If effective, the growth of breast cancer could be limited by herceptin.
In advanced cases of breast cancer, cancer growth and spreading are critical factors in the natural course of the disease. Limiting growth of cancer cells can extend survival time, limit metastasis, and improve quality of life of the advanced cancer patient.
Case Description: Sketch a basic clinical trial for Herceptin.
Case Objectives:
Describe the treatments, and the outcome(s) by which the treatments will be evaluated.
Last Ditch Approach – Applicable when you focus on BC cases without anymore treatment options.
Herceptin Group
PLACEBO Group
Supplemental Approach – Applicable when you focus on advanced BC cases with remaining treatment options.
Herceptin+Standard Treatment
PLACEBO+Standard Treatment
In either case, outcomes include:
Survival
Survival Time
Severity and Progression of BC
Remission
Identify the subject population for this trial.
As indicated earlier, this trial will focus on confirmed, advanced cases of BC – these cases typically exhibit:
Late Detection (Late Stage)
Cancer Cells Spread Distantly From Breast (Metastasis, Late Stage)
Cancer Cells Aggressive (Low Grade)
Discuss the assignment of subjects to the treatments in the trial.
Once appropriate BC cases have been recruited and screened, they are randomly assigned to either the Herceptin group or the PLACEBO group.
Only appropriate subjects who have given informed consent and who meet all inclusion requirements will be assigned to a treatment group.
Double blinding will be employed.
Case Study: Parkinson’s Disease
Definition
Parkinson's Disease (PD) is a chronic neurological condition named after Dr. James Parkinson, a London physician who was the first to describe the syndrome in 1817. PD is a slowly progressive disease that affects a small area of cells in the mid brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical known as dopamine. Parkinson's disease belongs to a group of conditions called motor system disorders. Parkinson's and related disorders are the result of the loss of dopamine-producing brain cells. Dopamine is a chemical messenger responsible for transmitting signals within the brain. Parkinson's disease occurs when certain nerve cells, or neurons, die or become impaired. Normally, these neurons produce dopamine. Loss of dopamine causes the nerve cells to fire out of control, leaving patients unable to direct or control their movement in a normal manner.
Symptoms
The four primary symptoms of Parkinson's are tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability or impaired balance and coordination. Patients may also have difficulty walking, talking, or completing other simple tasks.
Other symptoms observed in some persons with Parkinson's disease can include:
Small cramped handwriting (micrographia);
Lack of arm swing on the affected side;
Decreased facial expression (hypomimia);
Lowered voice volume (dysarthria);
Feelings of depression or anxiety;
Episodes of feeling "stuck in place" when initiating a step...called "freezing";
Slight foot drag on the affected side;
Increase in dandruff or oily skin;
Less frequent blinking and swallowing
Few patients experience all of these symptoms and some may experience other signs.
Treatment
Levodopa is often the first-line treatment for the disease. Levodopa helps restore muscle control when it is converted to dopamine in the brain.
Levodopa mixed with Carbidopa, a drug that is marketed as Sinemet. Carbidopa delays the conversion of levodopa to dopamine until it reaches the brain, often lessening or even preventing levodopa side effects. Carbidopa also decreases the amount of levodopa needed.
Other Levodopa Cocktails. These are combinations of Levidopa, which serves as a source of Dopamine when metabolized, and supplementary agents that simulate Dopamine, or protect and assist the metabolized Levodopa.
Side Effects of Levodopa
When levodopa is taken orally, a portion of the dose is converted to dopamine by the enzyme dopa-decarboxylase before it can enter the brain. This frequently causes side effects such as nausea, vomiting, loss of appetite, rapid heart rate, and lowered blood pressure when a person rises from a sitting to a standing position.
For this reason, levodopa is almost always given in combination with a medication called carbidopa, which blocks dopa-decarboxylase outside the brain, allowing more levodopa to enter the brain. This dramatically decreases the occurrence of the side effects listed above. Carbidopa itself, at doses used to treat PD, has not been associated with significant side effects.
Dopamine Receptor Agonists.
The pharmacologic action of a dopamine agonist is different from that of levodopa. Levodopa is converted in the brain into dopamine. In contrast, dopamine agonists act directly on dopamine receptors in the brain, and thus can help alleviate the symptoms of Parkinson's disease.
The most commonly used dopamine agonists in the U.S. include:
Dopamine agonists act on the receptors in the brain to which dopamine binds. There are at least five different dopamine receptors, subdivided into two main classes known as D1 and D2. Some of these receptors involve motor control, while others involve cognition.
Side Effects of Dopamine Receptor Agonists
Most of the reported side effects of all dopamine agonists are the same as those attributed to levodopa. This is because both levodopa and dopamine agonists replenish or mimic dopamine. Side effects can include nausea and vomiting, sleepiness, insomnia, dizziness, hallucinations, confusion, and low blood pressure occasionally associated with fainting. Dyskinesias (involuntary movements) may be worsened in individuals who are taking levodopa, which often permits a decreased dose of carbidopa/levodopa or Sinemet CR®.
Progression
The disease is both chronic and progressive. Early symptoms are subtle and occur gradually.
Parkinson's disease often begins with an episodic tremor of the hand on one side of the body. Tremors may be distressing because of their visibility to others, but fortunately, this symptom rarely lead to serious disability (approximately 25%, of PD patients do not even have tremors).
Resting tremors may be accompanied over time with slowness and stiffness on the affected side. As symptoms progress, patients may notice impairment on the other side of the body, almost always less severe than the primary side. Due to fine motor deficits, finger and hand movements requiring skilled coordination--such as brushing teeth, shaving, and buttoning clothes may become slow and difficult. Some patients notice a slight foot drag on the affected side, or a feeling of walking with great effort ("as if through quicksand") at times. Steps become shorter, or freezing (described earlier) may occur when initiating movement. The voice can become softer in volume and take on a raspy quality.
Many Parkinson patients do at some point experience gait and balance problems. Difficulty navigating doorways and narrow passages, stutter-steps, and precarious balance on turning are common examples of Parkinsonian gait disturbance. Preventing falls and subsequent injuries becomes a major priority.
Comparative Clinical Trial
Suppose that we have a new dopamine receptor agonist, MCDRA, that specifically and selectively stimulates the motor-control-related dopamine receptors. Sketch a comparative trial of MCDRA against Pramipexole (Mirapex®).
Early Diagnosis/Stage Approach – Applicable when you focus on early PD cases who have not yet started Levodopa.
MCDRA Group
Mirapex Group
Supplemental Approach – Applicable when you focus PD cases who require treatment.
MCDRA+Standard Treatment (Levodopa etc.)
Mirapex+Standard Treatment (Levodopa etc.)
We track our subjects for the appearance and severity of the primary symptoms:
tremor or trembling
rigidity or stiffness
bradykinesia
postural instability or impaired balance and coordination
We also track our subjects for the appearance and severity of other symptoms:
Small cramped handwriting (micrographia);
Lack of arm swing on the affected side;
Decreased facial expression (hypomimia);
Lowered voice volume (dysarthria);
Feelings of depression or anxiety;
Episodes of feeling "stuck in place" when initiating a step...called "freezing";
Slight foot drag on the affected side;
Increase in dandruff or oily skin;
Less frequent blinking and swallowing
We also consider side effects and toxicity.
Identify the subject population for this trial.
As indicated earlier, this trial will focus on cases of Parkinson's Disease.
Discuss the assignment of subjects to the treatments in the trial.
Once appropriate PD cases have been recruited and screened, they are randomly assigned to either the MCDRA group or the Mirapex group.
Only appropriate subjects who have given informed consent and who meet all inclusion requirements will be assigned to a treatment group.
Double blinding will be employed.
Learn More about Parkinson’s Disease:
http://neurosurgery.mgh.harvard.edu/pdstages.htm
http://www.parkinson.org/eduindex.htm
http://www.ninds.nih.gov/health_and_medical/disorders/parkinsons_disease.htm
http://www.fda.gov/fdac/features/1998/498_pd.html
http://jama.ama-assn.org/issues/v284n15/ffull/jed00075.html
http://www.parkinson.org/med3.htm
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.