Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12-Week, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study With Follow-Up Evaluating The Safety And Efficacy Of Varenicline Tartrate (CP-526,555-18) 1 Mg Bid For Smoking Cessation (Protocol A3051080)
Brief Summary: The primary objective of this protocol is to evaluate 12 weeks of treatment of varenicline compared to placebo for smoking cessation. Abstinence from cigarette smoking and other tobacco products (e.g., pipe, cigars, chew, snuff.) use during non-treatment follow-up period will also be evaluated.


Options:
A: Inclusion Criteria:

* Current male or female cigarette smokers who are motivated to stop smoking.
* Smoked an average of 10 cigarettes per day during past year and the month prior to first visit.

Exclusion Criteria:

* Patients who have used a nicotine replacement product, bupropion, clonidine or notriptyline within the past 6 months.
* Patients currently with depression or diagnosed with depression in past 12 months.
* Past or present history of psychosis, panic disorder, or bipolar disorder.
B: We are only recruiting by invitation only (to members of our past cohort). We will open up enrollment to the public in the Madison, WI and Milwaukee WI areas at the end of 2012.

Inclusion Criteria:

a. To be eligible for the Comparative effectiveness trial, participants must:

* smoke 5 or more cigarettes per day,
* desire to quit smoking but not be currently engaged in cessation treatment,
* be medically eligible to use either combination NRT or varenicline,
* have reliable phone access,
* if female, must not be pregnant and must be willing to use an acceptable birth control method.

Exclusion Criteria:

1. There are no exclusion criteria for participating in the main health outcomes study, other than being unwilling to complete study assessments.
2. All smoking participants from new and original cohorts will be excluded from the cessation trial for the following reasons:

   * end-stage renal disease with hemodialysis;
   * prior suicide attempts within the last 5 years or current suicidal ideation;
   * diagnosis of and/or treatment for schizophrenia;
   * other psychotic disorders or bipolar disorder within the last 10 years;
   * current PHQ-9 score indicative of moderately severe depression;
   * severe untreated hypertension \>200/100 mmHg;
   * currently taking Wellbutrin, Zyban or bupropion;
   * hospitalized for a stroke, heart attack, congestive heart failure or diabetes within the last year;
   * used pipe tobacco, cigars, snuff or chew more than twice in the past week.

It should be noted that if any incidental findings appear in any of the cardiology tests (e.g., ultrasound, tonometry, ECG, or exercise stress test; see forms in Supplemental Information section of application), the study cardiologist (Dr. Stein or his designee) will be assign the participant to the non-randomized treatment arm and they will be given the nicotine patch and the same counseling intervention as CET participants. They will not be included in the CET analyses. This will be done to properly address the cardiovascular risk warning from the FDA regarding varenicline (Chantix).
C: Inclusion Criteria:

Eligible participants will be males and females

1. Between the ages of 18-65.
2. Smoke at least 10 cigarettes/day for the past 6 months.
3. Provide a baseline Carbon Monoxide (CO) reading greater than 10ppm at the Intake Session.
4. Are seeking smoking cessation treatment.
5. Plan to live in the area for the next 12 months.
6. Fluent English speaker.
7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and Health Insurance Portability and Accountability Act (HIPAA) form. All subjects must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are taking study medication (pills and patches) and for at least one month after the medication period ends. All female subjects of child-bearing potential should not be pregnant for the duration of the study.

Exclusion Criteria:

Smoking Behavior

1. Regular (daily) use of chewing tobacco, snuff or snus.
2. Current enrollment or plans to enroll in another smoking cessation or research program in the next 12 months.
3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 12 months.
4. Provide a baseline CO reading less than or equal to 10ppm at the Intake Session.

Alcohol/Drug Exclusion Criteria

1. History (within the last year) or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants), excluding nicotine.
2. Current use of cocaine and/or methamphetamines (urine drug screen at the Intake Session).
3. Current alcohol consumption that exceeds greater than 25 standard drinks/week.
4. Current alcohol abuse or dependence.
5. Current non-alcoholic psychoactive substance abuse or dependence.

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy, or lactating.
2. History of epilepsy or a seizure disorder.
3. Current medical problems for which transdermal nicotine is contraindicated including:

   * Allergy to latex.
   * History of kidney and/or liver disease, including transplant (self-report).
   * Uncontrolled hypertension (determined as a Systolic Blood pressure (SBP) reading greater than 160 and/or a Diastolic Blood Pressure (DBP) greater than 100).
4. Serious or unstable disease within the past 6 months.
5. History (last 6 months) of abnormal heart rhythms, tachycardia and cardiovascular disease (stroke, angina, heart attack) may result in ineligibility. These conditions will be evaluated on a case by case basis by the Study Physician.
6. Inability to provide a blood sample to be used to assess nicotine metabolite ratio.

Psychiatric Exclusion Criteria (as determined by self report \& MINI)

1. Current diagnosis of major depression. Persons with a history of major depression, if stable for 6 months or longer, are eligible, provided they are not excluded based on medications (below).
2. Any suicide risk score on MINI or self-reported suicide attempt on telephone screen.
3. Current or past hypomanic/manic episode.
4. History or current diagnosis of Post Traumatic Stress Disorder (PTSD).
5. History or current diagnosis of psychotic disorder, bipolar disorder, schizophrenia.

Medication Exclusion Criteria

1. Current use or recent discontinuation (within the last 14-days) of:

   * Smoking cessation medication (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix); NOTE: Once participants are found eligible for the study, they are instructed to use the smoking cessation medication provided to them by the study staff. If a subject reports an isolated (non-daily) instance of using a non-study smoking cessation medication, the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation.
   * Anti-psychotic medications.
   * Certain medications used to treat depression, including Wellbutrin, Monoamine Oxidase Inhibitors (MAOIs), and tricyclic antidepressants.
   * Prescription stimulants (e.g. Provigil, Ritalin, Adderall).
2. Current use of:

   * Nicotine replacement therapy (NRT); NOTE: Once participants are found eligible for the study, they are told they should only use the NRT provided to them by the study staff. If a subject reports an isolated (non-daily) instance of NRT use during the study, they may be permitted to continue.
   * Tagamet (cimetidine).
   * Heart medications such as digoxin, quinidine, nitroglycerin; use of these medications may result in ineligibility and will therefore be evaluated on a case-by-case basis by the Study Physician.
   * Anti-coagulants (e.g., Coumadin, Warfarin).
3. Daily use of:

   * Opiate-containing medications for chronic pain; if a participant reports taking an opiate-containing medication every day for the 14 days prior to the telephone screen and/or Intake Session, the participant will be ineligible.
   * Rescue Inhalers (e.g. albuterol, proventil, ventolin, or maxair)

General Exclusion

1. Any medical condition, illness, disorder or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
D: Inclusion Criteria:

1. Age: 18-65 years old
2. Smoking: \>/= 5 cigarettes per day within the 2 months preceding the screening visit and expired CO greater than or equal to 6 ppm.
3. Able to follow verbal and written instructions in English and complete all aspects of the study
4. Have an address and home telephone number where they may be reached
5. Provide informed consent and agree to all assessments and study procedures
6. Be the only participant in their household

Exclusion Criteria:

1. Within the month immediately preceding the screening visit; use of any form of tobacco product other than cigarettes on 3 or more days within a week only if the individual refuses to refrain from non-cigarette tobacco use during the course of this study
2. Within the month immediately preceding the screening visit; use of marijuana in any form on 3 or more days within a week
3. Within the two weeks immediately preceding the screening visit, involvement on more than 3 days in any formal smoking cessation activities
4. Current visual or auditory problems that in the opinion of the investigator would interfere with the completion of study assessments
5. Treatment on a continuous basis within 2 weeks before the screening visit: any contraindicated medication for Varenicline or Bupropion.
6. Uncontrolled hypertension or other major contraindications for Bupropion or Varenicline.
7. Severe renal impairment (CR Clearance \<30 ml/min/1.73 m2).
8. Laboratory evaluations outside normal limits and of potential clinical significance in the opinion of the investigator
9. Meet current criteria for psychiatric disorders or substance abuse as assessed by the MINI for items A, B, D, I, J, K, L, M and N, including a past manic or hypomanic episode as well as a lifetime psychotic disorder.
10. Subject rated as moderate to high on suicidality as assessed by the MINI.
11. Psychiatric hospitalization within 1 year of screening date.
12. A positive urine pregnancy test during the screening period. Women who are two years post menopausal, one year post-tubal ligation, or who have had a partial or full hysterectomy will not be subject to a urine pregnancy test.
13. Pregnant, breast-feeding, or of childbearing potential who is not protected by a medically acceptable, effective method of birth control while enrolled in the study
14. Use of Varenicline or Bupropion within two weeks before the screening visit.
15. History of hypersensitivity or allergic reaction to Varenicline, tricyclic antidepressant, Bupropion (Wellbutrin, Zyban) or similar chemical classes or any component of these formulations.
16. Subject considered by the investigator as unsuitable candidate for receipt of an investigational drug, or unstable to be followed up throughout the entire duration of the study.

Answer: A