Table 1.

Summary of Internal Industry Clinical Trials

Authors/ Company	Year	Product(s) Tested	Outcomes of Interest	Study Design	Age	Inclusion/ Exclusion Criteria	Stratification
Philip Morris (9)	2001	Accord Oasis Marlboro Lights Marlboro Ultra Lights Non-smoking	Biomarkers of exposure: COHb CO Nicotine and metabolites NNAL and NNAL-glucuronide NNK metabolites CO Mutagenicity Ames Test	N= 110 Duration: 8 days Controlled smoking 5-arm randomized switching design	Adult	Smoke 5–25 Marlboro Lights cigarettes per day	Gender Number of cigarettes per day (11, 11–20, 21 cigarettes/day)
			Biomarkers of effect: Blood pressure Pulse rate Body weight Hemoglobin Leucocytes Platelet Factor IV Von Willebrand Factor Fibrinogen C-reactive Protein LDL, HDP Cholesterol Hematology Factor VII Leukotriene B4 Creatine 11-Dehydro-thromboxane B2 8-Epi-Prostaglandin F2α Myeloperoxidase Interleukin-8 Elstasc/α1-Antitrypsin complex
Philip Morris (17)	2001	Oasis (3mg FTC tar) Marlboro Lights (6mg) Parliament Extra Light (3mg) PM One (1mg) Cessation	Biomarkers of exposure: COHb Nicotine metabolites NNK metabolites	N=100 Duration: 10 days Confined ad-lib within-subject pre-post switching design	Not avail- able	Usual brand is Marlboro Lights	Not available
			Biomarkers of effect: Urinary mutagenicity Induced sputum inflammatory substance
			Behavioral and subjective: Smoking diaries
Philip Morris (proposed) (17)	2001	Oasis (3mg FTC tar) Usual brand (6,3, and 1 mg tar) control group	Biomarkers of exposure: COHb Nicotine metabolites NNK metabolites	N=100–200 Duration: 6 months Ad-lib switching study	Not avail- able	Not available	Not available
			Biomarkers of effect: Urinary mutagenicity Induced sputum inflammatory substance
			Behavioral and subjective: Smoking diaries
Roethig et al, Philip Morris (8)	2002	Conventional Cigarettes (FTC tar: 11mg and 3mg; nicotine: 0.8mg and 0.3mg) Electrically Heated Cigarettes (FTC tar: 3mg and 2mg; nicotine: 0.3mg and 0.2mg) Non-smoking	Biomarkers of exposure: COHb	N=110 Duration: 10 days Controlled smoking 5-arm randomized switching design	Adult	Male and female Healthy Smoke 5–25 cigarettes per day	Gender Number of cigarettes smoked per day
Philip Morris (13)	2002	Accord Marlboro Lights	Biomarkers of exposure COHb Venous bicarbonate Nicotine Cotinine Acute health effects:     Cardiopulmonary exercise     testing: Breathing frequency Minute ventilation Oxygen uptake CO production Gas exchange ratio Heart rate Blood pressure 12-lead electrocardiogram (EKG)	N=18 Duration: 3 3-day periods Confined randomized within-subject 3-condition switching design	40–70	Males Smoke ≥20 cig/day Smokers for at least 10 years Peak on enrollment and screening cardiopulmonary exercise tests must be within 10% of each other Do not regularly participate in competitive or organized recreational physical activities Body mass index (BMI) must be <40 kg/m2 No history of coronary artery, cerebrovascular, or pulmonary disease, other cardiac disease, cardiac dysrhythmia, conduction disturbance, acute pericarditis, myocarditis, endocarditis, lower extremity peripheral vascular disease, aortic aneurysm No malignancies within 5 years prior to screening except basal or squamous cell carcinoma No clinically significant gastrointestinal, renal, hepatobiliary, hematopoietic, neurologic, or rheumatologic disorder or chronic infections disease No clinically significant endocrine disorder except diet-controlled diabetes mellitus Type II and hypothyroidism controlled with stable dose for at least 3 months prior to enrollment No acute illness, significant trauma, or major surgery within 6 months of enrollment No physical handicap or condition that would limit lower body physical exercise No unstable psychiatric disorder or inability to comply with testing procedures No history within past 5 years or current use of illicit drugs No history within the past 5 years of excess alcohol use or current use of more than 2 units/day or 14 units/week No use of prohibited medications (included in appendix of cited document)	Not available
Philip Morris (Total Exposure Study) (7,29)	2005	Usual brand (<3.0 mg FTC tar, 3.0–6.9mg, 7.0–12.9mg, >12.9mg)	Biomarkers of exposure: Acetonitrile (exhalate and blood) CO (exhalate) COHb (blood) Hb adducts of 3- and 4-aminobiphenyl (blood) Nicotine (urine) Nicotine metabolites (urine) NNAL and NNAL-glucuronide (urine) Calcium (blood)	N=5000 (4 groups of 1000 smokers by FTC tar yield, 1000 non-smoking controls) Observational, cross-sectional, multi-center study with two assessment visits	Adult	Not available	Age Gender Body Mass Index Geographic region Ethnic and racial distribution SES (income and education)
			Biomarkers of effect: HDL- and LDL-cholesterol (Atherosclerosis) Triclycerides (Atherosclerosis) Fibrinogen (Cardiovascular disease) hs C-reactive protein (Tissue injury) Total billrubin (depletion of antioxidant capacity) Von Willebrand factor (endothelial cell damage) Microalbumin (endothelial cell damage) 11-Dehydrothromboxane-B2 (platelet activation)
			8-epi-Prostaglandin-F2α
RJ Reynolds (pp 498–504)(19)	1988	Premier Reference cigarette (unspecified)	Biomarkers of exposure: Nicotine (urine) Cotinine (urine)	N=72 (31 smokers, 41 non-smoker controls) Duration: 42 days Ad-lib within-subject double crossover design Controlled diet Monitored consumption of prescription and nonprescription therapeutic drugs Minimal exposure to chemicals, environmental smoke, and car exhaust	27–50	Not available	Gender Age
			Biomarkers of effect: Urine mutagenicity
			Behavioral and subjective Puff profiles
			Food diary
RJ Reynolds (18)	1996	Premier	Biomarkers of exposure:	N=23 or N=24 Duration: 2–3 weeks Ad-lib within-subject pre-post switching design	Not avail- able	Usual brand is Premier or conventional cigarette (no specified brand or tar level) for at least one year
			Behavioral and subjective: Sensory attribute ratings
Stiles et al, RJ Reynolds (10)	1997	Eclipse Regular Eclipse Mild Conventional cigarette (usual brand)	Biomarkers of exposure: CO Serum nicotine COHb	N=47 (23 Eclipse Regular, 24 Eclipse Mild) Ad-lib within-subject pre-post switching design Duration: 2 weeks (Eclipse Mild) or 3 weeks (Eclipse Regular)	31–54	Smoke ≥20 full flavor or low-tar cigarettes per day Good physical health
			Behavioral and subjective: Puffing profiles
			Sensory attribute ratings
RJ Reynolds (30)	1999	Eclipse	Biomarkers of exposure: Cotinine (urine) COHb CO	N=80 Duration: 48 weeks Ad-lib within-subject pre-post switching design	19+	Smoke ≥15 cigarettes/day Meet ATS criteria for chronic bronchitis
			Biomarkers of effect: Platelet count
			Acute health effects: Lung functioning Airway inflammation Respiratory symptoms
RJ Reynolds (15)	1997	Eclipse	Biomarkers of exposure: Nicotine (urine) Cotinine (saliva) Nicotine metabolites Urine mutagenicity	N=36 (24 smokers, 12 nonsmokers) Duration: 4 weeks Ad-lib within-subject pre-post switching design	26–59	Subjects’ workplace do not have smoking bans
			Behavioral and subjective: Puff profiles
Reynolds (11,31)	2004	Eclipse New Eclipse prototype (3% urea added)	Biomarkers of exposure: COHb Nicotine (blood)	N=36 Duration: 28 days Ad-lib within-subject double crossover design	21–55	Smoke full flavor, low tar, or ultra low tar cigarettes Smoke usual brand for at least six months Smoke ≥15 cigarettes per day Non-RJR employees No history of heart disease, lung disease, diabetes, liver disease, kidney disease, drug abuse, neurological disorders, or psychiatric illness.	•
RJ Reynolds (20)	2006	Eclipse Snus Low-Tar, Low-Nicotine Conventional Cigarette	Acute health effects: COPD-related health status measures	N=2700 Duration: 24 weeks Ad lib 3-arm randomized switching design	35–55	Male and female Smoke >15 cig/day Smoked for >10 years Free of clinically significant health problems as assessed by the study PI Negative pregnancy test at baseline, 12, and 24 weeks among female subjects Subjects over 55 excluded due to risk of undiagnosed atherosclerotic cardiovascular disease	Regular brand (Full-Flavor, Low-Tar, Ultra Low-Tar, Menthol)