Tobacco Use
Conditions
Keywords
Cigarette smoking
Brief summary
This study is proposing a four condition Electronic Tobacco Marketplace (ETM) study to determine if banning normal nicotine content (NNC) is sufficient for encouraging smokers to switch to potentially less harmful products or if the availability of higher nicotine and/or flavored alternative products (specifically e-cigarettes) are needed to achieve maximal reductions in smoking.
Detailed description
The Family Smoking Prevention and Tobacco Control Act (FSPTCA) passed in 2009 provides the FDA with the authority to regulate tobacco products. One provision in this legislative act empowers the FDA to set limits on constituents in tobacco products, including nicotine. Such a measure has the potential to reduce the chance of individuals experimenting with smoking from becoming dependent and enable current smokers to quit when they are motivated to do so. Although the proposal to reduce nicotine in cigarettes has been met with skepticism by some because of concerns over compensatory smoking behavior and the potential emergence of a black market, this policy measure was considered to be technically feasible by the American Medical Association and the British Medical, by tobacco control researchers, policymakers and governmental officials who were convened in a meeting on nicotine regulation8, and by the World Health Organization Study Group on Tobacco Product Regulation. Most importantly, in July 2017, FDA Commissioner Gottlieb announced he was directing our Center for Tobacco Products to develop a comprehensive nicotine regulatory plan premised on the need to confront and alter cigarette addiction. This announcement was followed on March 16, 2018 by the release of the Advance Notice of Proposed Rulemaking entitled Tobacco Product Standard for Nicotine Level of Combusted Cigarettes (ID: FDA-2017-N-6189-0001) to obtain information for consideration in developing a tobacco product standard to set the maximum nicotine level for cigarettes. This study proposes to conduct a within-subjects, multi-session virtual lab study and validation field assessment to determine how the availability of flavored e-liquids affects product purchasing among cigarette smokers. Adult daily cigarette smokers (N=64) will be recruited for this study. After initial eligibility is assessed, participants will complete six virtual sessions (1 baseline, 4 experimental, and 1 follow-up) and one field assessment to evaluate their tobacco use.
Interventions
OTHERNormal Nicotine Content Vape with all flavor e-liquids
Participants are randomly assigned to the order of each marketplace Group
OTHERNormal nicotine content vape with tobacco e-liquids
Participants are randomly assigned to the order of each marketplace Group
OTHERLow nicotine content vape with all flavor e-liquids
Participants are randomly assigned to the order of each marketplace Group
OTHERLow nicotine content vape with tobacco e-liquids
Participants are randomly assigned to the order of each marketplace Group
Sponsors
National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Masking description
Participants are told their shopping trips are randomly selected, when they are actually being randomly selected between the two marketplace groups where only one flavor of e-liquid is available.
Intervention model description
Participants are randomly assigned to either low nicotine or normal nicotine content vaping devices with tobacco flavors only available
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 21+ years of age * Self-report smoking at least 5 cigarettes per day for the past year * Breathe carbon monoxide (CO) level \> 8 ppm or positive urine NicCheck * Willingness to use other tobacco products during the study * Speak, comprehend, and read English sufficiently to complete study procedures * Have home access to a computer, smart phone, or tablet with a web camera and internet access * Tried a vaping device at least once in their lifetime
Exclusion criteria
* Currently seeking treatment to quit smoking * Self-reported serious medical or psychiatric condition(s) including cardiovascular and chronic respiratory diseases * Body temperature \> 100.4 F * Cold, flu or COVID-19 symptoms including fever, cough, and runny nose in the past 30 days * Currently pregnant, breastfeeding or intending to become pregnant for the duration of the study or unwilling to agree to use adequate protection to avoid pregnancy * CO reading \> 80 ppm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cigarettes Purchased | Visit 6 approximately 4 weeks after baseline | Average number of cigarettes purchased (analyzed as raw data and using derived behavioral economic measures) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lung Cancer Perceived Risk Scores for VLNC Cigarettes | Baseline | The response options rely on a 10-point Likert-like scale: 1 = very low risk of disease; 2, 3, 4, 5, 6, 7, 8, 9, 10 = very high risk of disease. Minimum possible response 1. Maximum possible response 10. The higher the score, the greater perceived risk of VLNC cigarettes for lung cancer. |
| Minnesota Nicotine Withdrawal Scale Scores | Visit 6 approximately 4 weeks after baseline | Minnesota Nicotine Withdrawal Scale measures the severity of nicotine withdrawal symptoms. The response options rely on a 5-point Likert-like scale; 0=None; 1= Slight; 2=Mild; 3=Moderate; 4=Severe. There are 7 items total, that are summed. Minimum possible response: 0. Maximum possible response: 28. Higher scores denote greater severity of withdrawal symptoms. |
| Questionnaire on Smoking Urges Score | Visit 6 approximately 4 weeks after baseline | Questionnaire on Smoking Urges measures the strength of urges to smoke. The response options rely on a 7-point Likert-like scale: 1=Strongly Disagree; 2; 3; 4; 5; 6; 7= Strongly Agree. The questionnaire has 10 total items; scores sum responses to each item. Minimum possible response: 10. Maximum possible response: 70. Higher scores denote greater urges to smoke. |
| Tobacco Product Interest Scores | 1 month after baseline | Tobacco Product Interest of different products; Slider scale ranging from 0=No Interest to 100=Very Interested |
| Tobacco Policy Questionnaire Scores | 1 month after baseline | Tobacco Policy Questionnaire scored from Support, Oppose, and Don't know for personal opinions on Making Cigarettes Less Addictive |
| Number of E-liquid Milliliters Purchased | Visit 6 approximately 4 weeks after baseline | Average number of e-liquid milliliters purchased (analyzed as raw data and using derived behavioral economic measures) |
| Proportion of Participants Completing Flavor and Nicotine Content Discrete Choice Projections | Month 1 after baseline | The proportion of participants projected to choose a cigarette over an e-cigarette under different potential regulatory scenarios, as determined by regression analysis. |
| Product Evaluation Scale Scores | Visit 6 approximately 4 weeks after baseline | Product evaluation scale scores for VLNC cigarettes among participants who received VLNC cigarettes will be determined by a product evaluation questionnaire. The questionnaire measures the strength of self-reported positive subjective effects (e.g., reward, satisfaction) following product use. The response options rely on a 7-point Likert-like scale: 1=not at all; 2= very little; 3= a little; 4= moderately; 5= a lot; 6= quite a lot; 7= extremely. The summed score adds responses to 13 separate items. Minimum possible response: 13. Maximum possible response: 91. Higher scores denote more favorable product effects. Note: This was only administered (at Virtual Visit 6) to participants who received each product type in the field (dependent on their baseline ETM shopping trip purchases). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of Exposure During Field Assessment - Carbon Monoxide | Screening visit through end of study (up to week eight) | Product use and biomarkers of exposure during the field assessment will be analyzed using linear regression or other appropriate regression models. The model for primary analysis of these data will include main effects for each of the two factors (for the ETM condition carried into the field assessment), and the corresponding baseline measure to improve precision. Carbon Monoxide (CO) is collected in ppm. |
| Biomarkers of Exposure During Field Assessment - Cotinine | Screening visit through end of study (up to week eight) | Product use and biomarkers of exposure during the field assessment will be analyzed using linear regression or other appropriate regression models. The model for primary analysis of these data will include main effects for each of the two factors (for the ETM condition carried into the field assessment), and the corresponding baseline measure to improve precision. Cotinine is collected in ng/ml. |
| Product Use Themes Emerging From the Qualitative Interviews | Screening visit through end of study (up to week eight) | Participants are asked about their opinions and experiences using tobacco products other than their usual brand during the field assessment. |
| Tobacco Product Use During Field Assessment | Screening visit through end of study (up to week eight) | Participants are asked what products they had used and quantity every day during the field assessment. |
Countries
United States
Participant flow
Pre-assignment details
Out of the initial 69 participants enrolled, 5 people were lost to follow up or withdrew between screening eligible and getting randomized to a group leaving 64 participants randomized. Staff instructed participants that one iteration of the task would be randomly selected and would determine which products (flavor e-liquids or tobacco e-liquids) they would use during the assessment. In reality, participants were only randomly assigned to tobacco e-liquid and never assigned to flavor e-liquid.
Participants by arm
| Arm | Count |
|---|---|
| Normal Nicotine Content Vape With All Flavor E-liquids Normal Nicotine Content Vape with all flavor e-liquids
Normal Nicotine Content Vape with all flavor e-liquids: Participants are randomly assigned to the order of each marketplace Group | 0 |
| Normal Nicotine Content Vape With Tobacco E-liquids Normal nicotine content vape with tobacco e-liquids
Normal nicotine content vape with tobacco e-liquids: Participants are randomly assigned to the order of each marketplace Group | 32 |
| Low Nicotine Content Vape With All Flavor E-liquids Low nicotine content vape with all flavor e-liquids
Low nicotine content vape with all flavor e-liquids: Participants are randomly assigned to the order of each marketplace Group | 0 |
| Low Nicotine Content Vape With Tobacco E-liquids Low nicotine content vape with tobacco e-liquids
Low nicotine content vape with tobacco e-liquids: Participants are randomly assigned to the order of each marketplace Group | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Normal Nicotine Content Vape With Tobacco E-liquids | Low Nicotine Content Vape With Tobacco E-liquids | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 29 Participants | 61 Participants |
| Age, Continuous | 49.2 years STANDARD_DEVIATION 9.9 | 50.3 years STANDARD_DEVIATION 12.6 | 50.0 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 28 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 15 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 16 Participants | 31 Participants |
| Region of Enrollment United States | 32 participants | 32 participants | 64 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 29 | 0 / 0 | 0 / 32 |
| other Total, other adverse events | 0 / 0 | 1 / 29 | 0 / 0 | 2 / 32 |
| serious Total, serious adverse events | 0 / 0 | 0 / 29 | 0 / 0 | 0 / 32 |
Outcome results
Primary
Number of Cigarettes Purchased
Average number of cigarettes purchased (analyzed as raw data and using derived behavioral economic measures)
Time frame: Visit 6 approximately 4 weeks after baseline
Population: Among those participants who purchased cigarettes in Shopping Trip 7 at Virtual Visit 6, the average number of cigarettes purchased (in an experimental tobacco marketplace where packs of very low nicotine content (VLNC) cigarettes, bottles of e-liquid matched to their randomization condition, boxes of nicotine gum were available).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Number of Cigarettes Purchased | 154.7 average number of cigarettes | Standard Deviation 131.7 |
| Low Nicotine Content Vape With Tobacco E-liquids | Number of Cigarettes Purchased | 119.2 average number of cigarettes | Standard Deviation 55.5 |
Secondary
Lung Cancer Perceived Risk Scores for VLNC Cigarettes
The response options rely on a 10-point Likert-like scale: 1 = very low risk of disease; 2, 3, 4, 5, 6, 7, 8, 9, 10 = very high risk of disease. Minimum possible response 1. Maximum possible response 10. The higher the score, the greater perceived risk of VLNC cigarettes for lung cancer.
Time frame: Baseline
Population: Group average for responses using a 10-point Likert-like scale: 1 = very low risk of disease; 2, 3, 4, 5, 6, 7, 8, 9, 10 = very high risk of disease. Minimum possible response 1. Maximum possible response 10. The higher the score, the greater perceived risk of VLNC cigarettes for lung cancer.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Lung Cancer Perceived Risk Scores for VLNC Cigarettes | 5.4 score on a scale | Standard Deviation 2.9 |
| Low Nicotine Content Vape With Tobacco E-liquids | Lung Cancer Perceived Risk Scores for VLNC Cigarettes | 4.2 score on a scale | Standard Deviation 2.9 |
Secondary
Minnesota Nicotine Withdrawal Scale Scores
Minnesota Nicotine Withdrawal Scale measures the severity of nicotine withdrawal symptoms. The response options rely on a 5-point Likert-like scale; 0=None; 1= Slight; 2=Mild; 3=Moderate; 4=Severe. There are 7 items total, that are summed. Minimum possible response: 0. Maximum possible response: 28. Higher scores denote greater severity of withdrawal symptoms.
Time frame: Visit 6 approximately 4 weeks after baseline
Population: Group averages, summed score of 7 items Minnesota Nicotine Withdrawal Scale measures the severity of nicotine withdrawal symptoms. The response options rely on a 5-point Likert-like scale; 0=None; 1= Slight; 2=Mild; 3=Moderate; 4=Severe. Minimum possible response: 0. Maximum possible response: 28. Higher scores denote greater severity of withdrawal symptoms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Minnesota Nicotine Withdrawal Scale Scores | 5.3 score on a scale | Standard Deviation 5.9 |
| Low Nicotine Content Vape With Tobacco E-liquids | Minnesota Nicotine Withdrawal Scale Scores | 4.9 score on a scale | Standard Deviation 7 |
Secondary
Number of E-liquid Milliliters Purchased
Average number of e-liquid milliliters purchased (analyzed as raw data and using derived behavioral economic measures)
Time frame: Visit 6 approximately 4 weeks after baseline
Population: Among those participants who purchased e-liquid in Shopping Trip 7 at Virtual Visit 6, the average number of mls purchased (in an experimental tobacco marketplace where packs of VLNC cigarettes, bottles of e-liquid matched to their randomization condition, boxes of nicotine gum were available).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Number of E-liquid Milliliters Purchased | 36.7 average number of milliliters | Standard Deviation 24.1 |
| Low Nicotine Content Vape With Tobacco E-liquids | Number of E-liquid Milliliters Purchased | 35.0 average number of milliliters | Standard Deviation 29.6 |
Secondary
Product Evaluation Scale Scores
Product evaluation scale scores for VLNC cigarettes among participants who received VLNC cigarettes will be determined by a product evaluation questionnaire. The questionnaire measures the strength of self-reported positive subjective effects (e.g., reward, satisfaction) following product use. The response options rely on a 7-point Likert-like scale: 1=not at all; 2= very little; 3= a little; 4= moderately; 5= a lot; 6= quite a lot; 7= extremely. The summed score adds responses to 13 separate items. Minimum possible response: 13. Maximum possible response: 91. Higher scores denote more favorable product effects. Note: This was only administered (at Virtual Visit 6) to participants who received each product type in the field (dependent on their baseline ETM shopping trip purchases).
Time frame: Visit 6 approximately 4 weeks after baseline
Population: Group Averages, summed score of 13 items The product evaluation questionnaire measures the strength of self-reported positive effects (e.g., reward, satisfaction) following product use. The response options rely on a 7-point Likert-like scale: 1=not at all; 2= very little; 3= a little; 4= moderately; 5= a lot; 6= quite a lot; 7= extremely. Only administered to participants who received each product type in the field.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Product Evaluation Scale Scores | 29.1 score on a scale | Standard Deviation 15.3 |
| Low Nicotine Content Vape With Tobacco E-liquids | Product Evaluation Scale Scores | 29.1 score on a scale | Standard Deviation 17 |
Secondary
Proportion of Participants Completing Flavor and Nicotine Content Discrete Choice Projections
The proportion of participants projected to choose a cigarette over an e-cigarette under different potential regulatory scenarios, as determined by regression analysis.
Time frame: Month 1 after baseline
Population: Scores reveal how important each product characteristic is to a participant when indicating their preference for one product over another (0 to 100, summing to 100). In our study, product type (2 levels: cigarette or e-cigarette), cigarette nicotine content (2 levels: normal or very low), e-liquid nicotine content (2 levels: 25mg/ml or 50mg/g) and available e-liquid flavor (2 levels: mint, fruit, sweet, tobacco or only tobacco) were manipulated in the discrete choice experiment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Proportion of Participants Completing Flavor and Nicotine Content Discrete Choice Projections | 41.8 Proportion of participants |
| Low Nicotine Content Vape With Tobacco E-liquids | Proportion of Participants Completing Flavor and Nicotine Content Discrete Choice Projections | 61.9 Proportion of participants |
Secondary
Questionnaire on Smoking Urges Score
Questionnaire on Smoking Urges measures the strength of urges to smoke. The response options rely on a 7-point Likert-like scale: 1=Strongly Disagree; 2; 3; 4; 5; 6; 7= Strongly Agree. The questionnaire has 10 total items; scores sum responses to each item. Minimum possible response: 10. Maximum possible response: 70. Higher scores denote greater urges to smoke.
Time frame: Visit 6 approximately 4 weeks after baseline
Population: Group averages, summed score of 10 items Questionnaire on Smoking Urges measures the strength of urges to smoke. The response options rely on a 7-point Likert-like scale: 1=Strongly Disagree; 2; 3; 4; 5; 6; 7= Strongly Agree. The questionnaire has 10 total items; scores sum responses to each item. Minimum possible response: 10. Maximum possible response: 70. Higher scores denote greater urges to smoke.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Questionnaire on Smoking Urges Score | 36.1 score on a scale | Standard Deviation 18.7 |
| Low Nicotine Content Vape With Tobacco E-liquids | Questionnaire on Smoking Urges Score | 32.4 score on a scale | Standard Deviation 19.2 |
Secondary
Tobacco Policy Questionnaire Scores
Tobacco Policy Questionnaire scored from Support, Oppose, and Don't know for personal opinions on Making Cigarettes Less Addictive
Time frame: 1 month after baseline
Population: Ppts were not actually randomized to all flavor e-liquid groups.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Policy Questionnaire Scores | Oppose | 7 Participants |
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Policy Questionnaire Scores | Don't Know | 7 Participants |
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Policy Questionnaire Scores | Support | 15 Participants |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Policy Questionnaire Scores | Oppose | 11 Participants |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Policy Questionnaire Scores | Support | 11 Participants |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Policy Questionnaire Scores | Don't Know | 10 Participants |
Secondary
Tobacco Product Interest Scores
Tobacco Product Interest of different products; Slider scale ranging from 0=No Interest to 100=Very Interested
Time frame: 1 month after baseline
Population: Product interest toward different cigarettes and e-cigarettes; Slider scale ranging from 0 = No Interest to 100 = Very Interested~Ppts were not actually randomized to all flavor e-liquids
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | Pod E-Cig | 38.3 score on a scale |
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | Mod E-Cig | 15.4 score on a scale |
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | VLNC | 27.1 score on a scale |
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | Pen E-Cig | 31.0 score on a scale |
| Normal Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | UB Cigs | 87.2 score on a scale |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | Pen E-Cig | 40.3 score on a scale |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | UB Cigs | 88.4 score on a scale |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | VLNC | 32.2 score on a scale |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | Mod E-Cig | 35.6 score on a scale |
| Low Nicotine Content Vape With Tobacco E-liquids | Tobacco Product Interest Scores | Pod E-Cig | 33.2 score on a scale |
Other Pre-specified
Biomarkers of Exposure During Field Assessment - Carbon Monoxide
Product use and biomarkers of exposure during the field assessment will be analyzed using linear regression or other appropriate regression models. The model for primary analysis of these data will include main effects for each of the two factors (for the ETM condition carried into the field assessment), and the corresponding baseline measure to improve precision. Carbon Monoxide (CO) is collected in ppm.
Time frame: Screening visit through end of study (up to week eight)
Other Pre-specified
Biomarkers of Exposure During Field Assessment - Cotinine
Product use and biomarkers of exposure during the field assessment will be analyzed using linear regression or other appropriate regression models. The model for primary analysis of these data will include main effects for each of the two factors (for the ETM condition carried into the field assessment), and the corresponding baseline measure to improve precision. Cotinine is collected in ng/ml.
Time frame: Screening visit through end of study (up to week eight)
Other Pre-specified
Product Use Themes Emerging From the Qualitative Interviews
Participants are asked about their opinions and experiences using tobacco products other than their usual brand during the field assessment.
Time frame: Screening visit through end of study (up to week eight)
Other Pre-specified
Tobacco Product Use During Field Assessment
Participants are asked what products they had used and quantity every day during the field assessment.
Time frame: Screening visit through end of study (up to week eight)