Key|The Second Hourly | Math 1107 | Spring 2009 | CJ Alverson

Protocol

You will use only the following resources: Your individual calculator; individual tool-sheet (one (1) 8.5 by 11 inch sheet), writing utensils, blank paper (provided by me) and this copy of the hourly. Do not share these resources with anyone else. Show complete detail and work for full credit. Follow case study solutions and sample hourly keys in presenting your solutions. Work all four cases. Using only one side of the blank sheets provided, present your work. Do not write on both sides of the sheets provided, and present your work only on these sheets. Do not share information with any other students during this hourly. When you are finished: Prepare a Cover Sheet: Print your name on an otherwise blank sheet of paper. Then stack your stuff as follows: Cover Sheet (Top), Your Work Sheets, The Test Papers, Your Toolsheet. Then hand all of this in to me.

Sign and Acknowledge:       I agree to follow this protocol. 

________________________________________________________________________

Name (PRINTED)                                             Signature                                             Date

Case One | Clinical Trial Sketch | Atomoxetine Augmentation Therapy in Patients With Alzheimer's Disease

(http://clinicaltrials.gov/ct2/show/NCT00191009?term=alzheimers&rank=2)

 

Atomoxetine (Strattera)  is a  norepinephrine reuptake inhibitors (NRIs), also known as noradrenaline reuptake inhibitors (NARIs). NARIs are compounds that elevate the extracellular level of the neurotransmitter norepinephrine in the central nervous system. Norepinephrine acts as a neurotransmitter, affecting cognitive awareness. Alzheimer’s disease is a form of progressive dementia.Symptoms include memory loss and other cognitive deficits, advancing to major personality changes and eventual loss of control over bodily functions. The hallmark of Alzheimer’s disease is the abnormally rapid and progressive loss of cognitive function, including memory, language and cognitive awareness. Patients with Alzheimer’s disease are assessed using the Alzheimer's Disease Assessment Scale, Clinician's Interview-Based Impression of Change, Neuropsychiatric Inventory (NPI) and Alzheimer's Disease Cooperative Study Inventory. Primary Outcome Measures: To see if Alzheimer's patients receiving a stable dose of an Alzheimer's drug randomly assigned to atomoxetine will have cognitive performance improved as measured by the Alzheimer's Disease Assessment Scale – Cognitive. Secondary Outcome Measures: To see if patients taking an Alzheimer's medication plus atomoxetine will be superior to an Alzheimer's medication alone as assessed by the Clinician's Interview-Based Impression of Change (CIBIC+) score. To see if patients taking an Alzheimer's medication plus atomoxetine will display less comorbid psychological symptoms, such as depression, as assessed by the Neuropsychiatric Inventory (NPI). To see if current Alzheimer's medications plus atomoxetine compared to Alzheimer's medications plus placebo is better at preserving or slowing cognitive decline as measured by the Alzheimer's Disease Cooperative Study Inventory – Activities.To show that current Alzheimer's drugs can be taken with atomoxetine without significant side effects.

 

Sketch a basic clinical trial for the use of atomoxetine  when used in addition to standard Alzheimer’s disease therapies in treating the progressive loss of cognitive functions. Make your sketch concise and complete, following the style demonstrated in class, in the second hourly and in case study summaries. 

We recruit patients diagnosed with Alzheimer’s disease (AD). Those who are eligible for the study and who give informed consent (or whose caregivers give informed consent by proxy) are enrolled in the study.

Enrolled subjects are randomly assigned to either atomoxetine + standard care or to placeboatomoxetine + standard care. Double blinding is employed, so that neither the patients(nor their caregivers)  nor the clinical workers know the individual treatment assignments.

Treated patients are tracked for changes in cognitive performance as assessed by the Alzheimer's Disease Assessment Scale – Cognitive, and as assessed by the Clinician's Interview-Based Impression of Change (CIBIC+) score. Treated patients are tracked for comorbid symptoms, including depression, as assessed by the Neuropsychiatric Inventory (NPI). Treated patients are tracked for cognitive decline as measured by the Alzheimer's Disease Cooperative Study Inventory – Activities. Treated patients are tracked for side effects and drug toxicity.

Case Two | Descriptive Statistics | Duchenne Muscular Dystrophy Survival Time

Duchenne muscular dystrophy (DMD) is an inherited disorder characterized by rapidly progressive muscle weakness which starts in the legs and pelvis and later affects the whole body. Suppose that we follow individuals diagnosed with DMD from diagnosis until death, noting age at death in months. Consider a random sample of individuals who were diagnosed with, and died with DMD. Age at death in months follows below:

34,  50, 75,  80, 85, 97, 100, 112,  120, 123, 127, 143, 150, 156, 161, 169, 173, 177, 179, 184, 185, 186, 189, 190 190, 193, 194, 196, 196, 197, 199, 200, 203, 204, 207, 210, 213, 215, 227, 228 230, 231, 233, 234, 235, 237, 265

Compute and interpret the following statistics: sample size, p00, p25, p50, p75, p100, (p75 – p25),

(p100 – p25), (p50-p25).  Show complete detail and work for full credit. Follow case study solutions and sample hourly keys in presenting your solutions.

 

Numbers

 

n    p00    p25    p50    p75    p100    range41    range31    range21

47     34    143    190    210     265      122         67         47

 

range41 = p100 – p25 = 265 – 143 = 122

range31 = p75 – p25 = 210 – 143 = 67

range21 = p50– p25 = 190 – 143 = 47

Interpretation

There are 47 patients with Duchenne muscular dystrophy (DMD) in the sample.

The shortest-lived DMD patient in the sample was aged 34 months at death.

Approximately 25% of the DMD patients in the sample were aged 143 months or less at death.

Approximately 50% of the DMD patients in the sample were aged 190 months or less at death.

Approximately 75% of the DMD patients in the sample were aged 210 months or less at death.

The longest-lived DMD patient in the sample was aged 265 months at death.

 

Approximately 75% of the DMD patients in the sample were aged between 143 and 265 months at death. The largest difference in age at death between any pair of DMD patients in the upper three-quarter sample is 122 months.

 

Approximately 50% of the DMD patients in the sample were aged between 143 and 210 months at death. The largest difference in age at death between any pair of DMD patients in the middle half sample is 67 months.

 

Approximately 25% of the DMD patients in the sample were aged between 143 and 190 months at death. The largest difference in age at death between any pair of DMD patients in the lower middle quarter sample is 47 months.

Case Three | Design Fault Spot: In each of the following a brief description of a design is presented. Briefly identify faults present in the design. Use the information provided. Be brief and complete.

1. A sample of college students is needed for a sample survey. The people running the study decide on the following: they divide the population of colleges and universities into groups based upon enrollment size and whether the college or university is private or public; next, they used judgment to select one school from each group. Then, a random sample of students was selected from each selected school.

The schools should be randomly sampled.

2. A sample survey design employs a random sample of the United Kingdom (England, Wales, Scotland, and Northern Ireland) adult subjects (18 years or older, non-institutionalized). The research objective of the survey is to determine attitudes of Irish* subjects regarding Birth Control. Assume that the Survey Instrument is written properly and delivered in an unbiased way.  * Ireland is split into two countries: Northern Ireland and Ireland

Respondents from Northern Ireland are excluded, and non-Irish respondents from the United Kingdom are included.

3. In a comparative clinical trial, treatment methods are compared in the treatment of Condition X, which when left untreated leads to severe complications and possibly death. 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 "moderate" subjects to the new surgical method. Only the "severe" subjects are assigned to the standard surgical method. A placebo group is also employed for the “mild” cases.

Treatments must be randomly assigned.

4. A clinical trial of a new Hepatitis C treatment is designed as follows: subjects are screened for Hepatitis C infection. Those who test positive for Hepatitis C infection are then told of their status, and are offered treatment for Hepatitis C at no cost, and are given no further information. Those who accept the free treatment offer are then randomly assigned to either a Placebo, or to the New Treatment Plan.

Abuse of informed consent; inappropriate use of placebo, denial of treatment

Case Four | Summary Intervals | The Framingham Heart Study

The objective of the Framingham Heart Study was to identify the common factors or characteristics that contribute to Cardiovascular disease (CVD) by following its development over a long period of time (since 1948)  in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke. Blood pressure is a measurement of the force applied to the walls of the arteries as the heart pumps blood through the body. Blood pressure readings are measured in millimeters of mercury (mm Hg) and usually given as 2 numbers. The top number is the systolic blood pressure reading. It represents the maximum pressure exerted when the heart contracts.  The bottom number is the diastolic blood pressure reading. It represents the pressure in the arteries when the heart is at rest. A sample of FHS adult subjects yields the following readings: (top/bottom)

124/88, 130/70, 175/75, 136/84, 124/84, 154/90, 160/92, 210/120, 110/75, 166/108, 100/70, 172/110, 160/90, 145/75, 122/84, 162/80, 156/84, 120/65, 130/90, 210/110, 110/68, 160/106, 140/90, 200/100, 165/105, 132/88, 134/84, 120/75, 138/85, 118/86, 152/74, 138/70, 124/74, 122/80, 155/90, 160/100, 294/144, 140/82, 132/86, 120/80, 200/130, 135/75, 140/78, 142/85, 146/94, 185/90, 166/78, 140/80, 120/80, 150/95, 124/75, 150/110, 140/84, 130/82, 130/80, 230/124, 128/72, 220/118, 130/80, 165/95, 208/114, 126/80, 140/90, 166/104, 130/70, 130/80, 120/90

Let m denote the sample mean, and sd the sample standard deviation. Compute and interpret the intervals 

m ± 2sd and m ± 3sd for diastolic  blood pressure (DBP), using Tchebysheff’s Inequalities and the Empirical Rule. Be specific and complete. Show complete detail and work for full credit. Follow case study solutions and sample hourly keys in presenting your solutions.

 

Numbers

 

If you analyze systolic blood pressure(SBP), you’ll get:

 

n          m         sd     lower2     upper2     lower3     upper3

67   149.4      33.35       82.7      216.1       49.4      249.5

 

But we want diastolic blood pressure(DBP):                         

 

n          m         sd     lower2     upper2     lower3     upper3

67       88.7      15.96       56.8      120.6       40.8      136.6

 

Lower2 = m – 2*sd » 88.7  2*15.96 » 56.8

Upper2 = m + 2*sd » 88.7  + 2*15.96 » 120.6

 

Lower3 = m – 3*sd » 88.7  3*15.96 » 40.8

Upper3 = m - 3*sd » 88.7  + 3*15.96 » 136.6

 

There are 67 Framingham Heart Study (FHS) subjects in the sample.

 

At least 75% of the FHS subjects in the sample present diastolic blood pressure(DBP) between 56.8 and 120.6 mmHg.

 

At least 89% of the FHS subjects in the sample present diastolic blood pressure(DBP) between 40.8 and 136.6 mmHg.

 

If the FHS subjects’ diastolic blood pressures cluster symmetrically around a central value, becoming rare as the distance from the center increases, then:

 

approximately 95% of the FHS subjects in the sample present diastolic blood pressure(DBP) between 56.8 and 120.6 mmHg and

 

approximately100% of the FHS subjects in the sample present diastolic blood pressure(DBP) between 40.8 and 136.6 mmHg.

 

 

 Work all four (4) cases.