dp13-003 foa final amendment 1 02.21.13.docx

Amendment 1 made 2.21.13:

Part 1. Overview Information, Key Dates, Scientific Merit Review; Secondary Review; Expiration date - Scientific Merit Review – April 2013; Secondary Review – June 2013; Expiration date – March 5, 2013

Section V. Application Review Information, Investigators third bullet should read “…follow up periods of at least three months after delivery?”; Approach, 6th bullet should read “…during a minimum of three months…”.

Section I. Funding Opportunity Announcement Description, and just immediately before 3.

Attachment 1 - Questions from potential applicants with answers by CDC Table of Contents

Part 1. Overview Information

Key Dates Publication Date

To receive notification of any changes to [RFA-DP-13-003], return to the synopsis page of this announcement at www.grants.gov and click on the “Send Me Change Notification Emails” link An email address is needed for this service.

On-time submission requires that electronic applications be error-free and made available to CDC for processing from eRA Commons on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov/eRA Commons no later than 5:00 PM U.S. Eastern Time. Note: HHS/CDC grant submission procedures do not provide a period of time beyond the application due date to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise in this FOA. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note: The Research Strategy component of the Research Plan is limited to 25 pages.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

“Apply electronically” at www.grants.gov

Executive Summary

· Purpose. The purpose of the FOA is to assist applicants with the preparation of an application that aligns with this announcement. The intent of this FOA is to solicit proposals to evaluate the effect of a smoking cessation intervention called contingency management (CM) on prenatal smoking cessation and to evaluate and assess the cost benefit of a high intensity and low intensity CM intervention. The suggested study design is a three-arm randomized controlled trial to assess smoking abstinence at end of pregnancy and cost-benefit of different intensity levels of CM on prenatal smoking cessation. The three arms include: 1) a high intensity CM intervention for smoking cessation during pregnancy; 2) a low intensity CM intervention for smoking cessation during pregnancy, and 3) standard of care.

· Mechanism of Support. The funding mechanism is a cooperative agreement.

· Funds Available and Anticipated Number of Awards. NCCDPHP intends to fund one (1) award and intends to commit approximately $2,800,000 in total (including both direct and indirect costs) over the entire project period. An award issued under this FOA is contingent upon availability of funds and a sufficient number of meritorious applications. The total amount awarded and the number of awards will depend upon the number, quality, duration, and cost of the applications received.

· Budget and Project Period. An applicant may request a project period of up to five (5) years. The estimated total funding (including both direct and indirect) is $560,000 for the first year (12 month budget period). The estimated total funding (direct and indirect) for the entire project period is $2,800,000. The project period will run from 09/30/2013 to 09/29/2018.

· Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. Application and Submission Information of this announcement.

· Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.

· Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

· Number of PDs/PIs. Applications may include more than one PI; however, the first PI listed will be the “contact PI” for all correspondence.

· Number of Applications. Eligible applicant institutions may submit only one application.

· Application Type. New

· Special Date(s). None.

· Application Materials. See Section IV.1 for application materials.

· Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (770) 488-2783.

Part 2. Full Text

Section I. Funding Opportunity Announcement Description

Statutory Authority This program is authorized under Section 301(a) of the Public Health Service Act, 42 U.S.C. 241(a).

1. Background and Purpose Nature of the Research Opportunity The nature of this research opportunity is to evaluate a contingency management (CM) intervention on prenatal smoking cessation and to evaluate and assess the cost benefit of a high intensity and low intensity CM intervention. The suggested approach is to conduct a three-arm Randomized Controlled Trial (RCT) to evaluate and assess smoking cessation at end of pregnancy and cost benefit of different intensity levels of CM on prenatal smoking cessation. The 3 arms include: 1) a high intensity CM intervention for smoking cessation during pregnancy; 2) a low intensity CM intervention for smoking cessation during pregnancy, and 3) standard of care. The results of this study will inform health care insurers and providers on the cost-benefit of providing a CM intervention for pregnant smokers.

Background In the US, the prevalence of smoking during pregnancy is estimated to be 10-13%, and certain subpopulations of women (e.g., low-income, Alaska Natives) and several states have rates as high as 30-45%. Additionally women who are low-income (e.g., Medicaid-enrolled) have prenatal smoking prevalence of 22%. The adverse effects of smoking on pregnancy outcomes are substantial: 5%–8% of preterm deliveries, 13%–19% of term low-birth-weight deliveries, 23%–34% of Sudden Infant Death Syndrome (SIDS), and 5%–7% of preterm-related deaths. Behavioral counseling (the first-line cessation intervention) is modestly effective, resulting in a cessation rate of only 5 out of 100 pregnant smokers. In contrast, CM interventions have been estimated to result in 24 out of 100 women quitting smoking by the end of pregnancy. CM interventions reinforce quitting with financial incentives, which increase as the length of abstinence increases.

Previous CM studies have shown that increased quitting among pregnant smokers led to reductions in the number of days infants spent in the neonatal intensive care unit, suggesting that CM interventions could result in significant cost savings. Recently published CM studies have tested intensive CM interventions in which smokers were required to undergo frequent abstinence monitoring: daily for the first week, twice a week for up to two months, once a week for 4 weeks, and then every other week until delivery.

For example, one CM study of pregnant smokers required women in the first week to report to the clinic every day for 5 consecutive days for abstinence monitoring which was assessed by carbon monoxide. Vouchers with a value of $6.25 were given if the woman was abstinent from smoking, and the value of the voucher increased by $1.25 for each consecutive visit for which she remained abstinent until the voucher reached the value of $45.00 when it remained constant. The frequency of the visits decreased to twice weekly for seven weeks and then decreased to every other week until delivery.

The effectiveness of lower intensity interventions in which smokers are required to undergo less frequent monitoring is unknown. Before promoting wide-scale dissemination of the CM model, it is important to know whether CM is a cost-savings approach to prenatal smoking cessation. If a CM intervention is found to be cost-saving, the intervention could be promoted to private and public insurance programs (e.g., Medicaid) through peer-review publications, presentations, and webinars. Given that staff time is one of the most expensive components of a CM intervention, estimating the cost-benefit of CM interventions at differing intensity levels would also be valuable. Insurers and providers could use the results generated from this study to determine the intensity of the CM intervention needed to increase smoking cessation among pregnant smokers, and to reduce costs associated with maternal and infant health care. Wider implementation of a highly effective smoking cessation intervention during pregnancy could result in better maternal and infant health outcomes and reduction in healthcare costs associated with pregnancy, delivery, and early infant care.

Purpose The purpose of this FOA is to solicit proposals to conduct a study that evaluates a contingency management (CM) smoking cessation intervention for pregnant smokers and to evaluate and assess the cost benefit of a high intensity and low intensity CM intervention. The suggested approach is to use a three-arm RCT design to assess smoking abstinence at end of pregnancy and cost-benefit of different intensity levels of CM on prenatal smoking cessation. The three arms include: 1) a high intensity CM intervention for smoking cessation during pregnancy; 2) a low intensity CM intervention for smoking cessation during pregnancy, and 3) standard of care.

Healthy People 2020 and other National strategic priorities - This research addresses several “Healthy People 2020” priority area(s):

a. Tobacco use, Objective TU-6, to increase smoking cessation during pregnancy, and

b. Maternal, Infant, and Child Health, Objective MICH-11, to increase abstinence from alcohol, cigarettes and illicit drugs among pregnant women.

This research addresses the CDC Winnable Battle to reduce tobacco use. In addition, this research is aligned with NCCDPHP performance goal(s) to define, conduct, and promote public health research in reproductive and infant health and with its strategic priority, Focus on Well-Being: Increase emphasis on promoting health and preventing risk factors, thereby reducing the onset of chronic health conditions. This program is aligned with all three of the CDC's Division of Reproductive Health's (DRH) goals: 1) improve women's reproductive health from menarche through menopause; 2) improve pregnancy health and care; and 3) improve fetal, newborn, and infant health.

Public Health Impact - Through this announcement, the CDC intends to fund one project that will have the potential to yield high impact research results by reducing public health burden and improving population health on a large scale. Wider implementation of a highly effective smoking cessation intervention during pregnancy could result in better maternal and infant health outcomes and reduction in healthcare costs associated with pregnancy, delivery, and early infant care.

2. Approach

Research Goals and Objectives The research goal of this FOA is to conduct a study that evaluates smoking cessation at the end of pregnancy and any cost-benefit of different intensity levels of a CM intervention for prenatal smoking cessation. The desired approach for the evaluation is a 3-arm RCT designed to increase smoking cessation at the end of pregnancy. The 3 arms include: 1) a high intensity CM intervention for smoking cessation during pregnancy; 2) a low intensity CM intervention for smoking cessation during pregnancy, and 3) standard of care.

In order to assess the effectiveness and cost-benefit of CM interventions with differing levels of intensity for smoking cessation among pregnant smokers, an RCT is needed with measures of overall medical costs and health outcomes for each of the CM intervention arms versus standard of care (e.g., behavioral counseling). The cost-benefit analysis should consider overall medical costs involved in the RCT, including both the program intervention costs and the reimbursed medical costs accrued during pregnancy, delivery, and up to 3-months postpartum for the mother and the infant. Primary health outcomes of interest are smoking cessation rates at end of pregnancy comparing the CM intervention arms to the standard of care. Secondary health outcomes include infant gestational age, infant birth weight, nights in the neonatal intensive care unit, mother and infant’s overall length of hospital stay, and maternal complications during pregnancy (including hospitalizations), and mother’s quit rate at 3 months post-delivery. The desired RCT would have three arms in which women would receive: 1) a high intensity CM smoking cessation intervention; 2) a low intensity CM smoking cessation intervention; and 3) standard of care. Intensity of the CM interventions would be defined by the number/frequency of visits in which study participants’ current smoking is biochemically assessed and at which incentives are provided to reinforce those who have remained abstinent. It is recommended that the values of the individual incentives received per visit are similar between the CM arms.

Objective 1: To design a study that assesses and compares abstinence of smoking at end of pregnancy and cost-benefit of CM interventions with differing levels of intensity for smoking cessation for women who entered prenatal care as smokers using random assignment to one of three study arms: 1) a high intensity CM intervention; 2) a low intensity CM intervention; and 3) standard of care. Components pertaining to this objective include:

· Developing the research protocol and submitting the protocol for human subjects review and for OMB clearance as required.

· Developing a process evaluation of key milestones of the project.

· Working collaboratively with CDC staff on the design, analyses, and dissemination of study results, including sharing de-identified data with CDC for secondary analyses.

· The suggested research design is a 3-arm RCT to increase smoking cessation among pregnant women, with the 3 arms including: 1) a high intensity CM intervention; 2) a low intensity CM intervention; and 3) standard of care (behavioral counseling).

· It is recommended that the high intensity CM intervention be modeled on proven effective prenatal smoking CM interventions published in peer-reviewed journals, showing approximately a 24% or greater reduction in smoking cessation by end of pregnancy compared to behavioral counseling. Such an intervention might include visiting a counselor daily for the two weeks, twice a week for up to two months, once a week for 4 weeks, and then every other week until delivery.

· The low intensity CM intervention must include fewer visits than the high intensity CM intervention, but enough to reinforce the quitting behavior, such as visiting a counselor twice a week for the first month, once a week for the next two months, and then every other week until delivery.

· The current standard of care for smoking cessation during pregnancy should reflect what is currently being implemented at the clinic(s) where the women are receiving prenatal care (e.g., behavioral counseling without medication).

· The estimated sample size must have 80% power to detect a clinically-meaningful difference in the biochemically verified abstinence of smoking at the end of pregnancy comparing each CM intervention arm to the standard of care arm. The study must also be powered to assess differences in cost-benefit among the 3 arms.

· It is recommended that the RCT inclusion criteria should include, but are not limited to: continued smoking after learning of pregnancy status, singleton pregnancies, and enrollment in the study within 16 weeks of estimated gestational age, no current known use of illicit drugs or heavy use of alcohol.

Objective 2: To implement the study and analyze data to assess all outcomes including cessation and medical costs, infant and maternal outcomes. Estimate the overall medical costs accrued during pregnancy and up to 3-months postpartum for prenatal smokers receiving high and low intensity CM interventions and those receiving standard of care, and to estimate cost-benefit ratios that compare each of the two intervention arms to the standard of care arm.

· Assess abstinence of smoking at each visit and at end of pregnancy for prenatal smokers receiving high and low intensity CM interventions and those receiving standard of care. Abstinence should be biochemically assessed based on recommended standards or tests for assessing cessation that have high sensitivity and specificity, particularly among pregnant women. Biochemical verification could include, for example, carbon monoxide testing and/or cotinine validation using urine.

· Estimate the overall medical costs accrued during pregnancy and up to 3-months postpartum for prenatal smokers receiving high and low intensity CM interventions and those receiving standard of care.

· Medical costs should include, but are not limited to: prenatal care costs, hospitalizations during pregnancy, delivery hospitalizations for the mother, and subsequent hospitalizations or medical costs occurred up to 3-months postpartum.

· Cost-benefit ratios should be estimated that compare each of the two arms to the standard of care arm.

· Intervention costs should include costs for implementing the CM interventions and providing standard of care including staff time, materials, incentives, and overhead.

· Assess and compare incidence of infant outcomes and health care service utilization during pregnancy, at delivery and up to 3 months of age for infants of women receiving the high and low intensity CM smoking cessation interventions and those receiving standard of care.

· Specify data sources or collection methods for data on infants: birth weight, gestational age, length of time in the neonatal intensive care unit, length of delivery hospitalization and re-hospitalization or medical care up to 3 months of age.

· Assess and compare incidence of maternal outcomes and health care service utilization during pregnancy, at delivery and up to 3 months postpartum for women receiving the high and low intensity CM smoking cessation interventions and those receiving standard of care.

· Specify data sources or collection methods for data on any hospitalizations during pregnancy, any medical complications during pregnancy, mother’s length of delivery hospitalization and any re-hospitalizations or medical care up to 3 months postpartum. Medical complications should include, but are not limited to, the following: pre-existing and gestational hypertension, maternal depression, maternal anxiety, placenta previa, premature rupture of membranes, placenta abruption.

Objective 3: To disseminate results and study findings, including publishing results in peer-reviewed journal(s)

· Write manuscript and collaborate with CDC consultants as co-authors.

· Submit manuscript through CDC clearance before submission to a peer-reviewed journal when CDC authors are included on the manuscript.

· Draft a dissemination plan that could guide efforts to disseminate the intervention to other sites.

Timeline - The general timeline for the project will consist of 3 phases over 5 years. Grantees will work closely with CDC collaborators on all activities defined below.

Phase 1: Development (Months 1-12)

· Design the 2 intervention components.

· Design the RCT study and data collection instruments to evaluate the interventions.

· Develop the research protocol for the RCT and submit the protocol for human subjects review.

· Establish a Data Safety and Monitoring Board.

· Register the trial with ClinicalTrials.gov.

· Prepare OMB package if necessary.

Phase 2: Intervention implementation (Months 13-48)

· Finalize intervention materials (by 18 months)

· Recruit and train staff to deliver the intervention and to conduct the evaluation study.

· Pilot test the intervention, revise design as needed.

· Enroll women into the study, conduct interventions and follow participants throughout pregnancy and through 3 months after delivery.

· Conduct quality assurance of intervention implementation and data collection.

Phase 3: Study findings, publications, and dissemination (Months 49-60)

· Complete study data collection (by 51 months).

· Analyze data to assess abstinence from smoking at delivery and cost-benefit of the interventions and submit papers reporting findings to peer-reviewed journals.

· Share de-identified data with CDC staff for secondary analyses.

Target population - The target population is pregnant smokers ages 18-44 years. The study population must include economically disadvantaged women as defined by at least 25% of the pregnant smoking women attending the prenatal clinics from the sites be Medicaid-insured pregnant women who continued smoking during pregnancy. Enrolling at least 25% of economically disadvantaged pregnant smokers is important because nationally, pregnant smokers are more likely to be low income and less educated than nonsmokers. Thus, having enough women with this background will allow for assessing whether this intervention is effective with pregnant smokers from a variety of backgrounds.

Collaboration/Partnerships - The applicant may consider developing partnerships with the tobacco control agencies and maternal and child health care agencies in the community where the study will take place.

Evaluation/Performance measurement - The applicant is expected to develop a process evaluation of key milestones of the project.

Translation plan - The application should address how research findings will be disseminated to key stakeholders.

OMB/PRA requirements are expected to apply.

3. Reference List Adams EK, Melvin CL, Raskind-Hood C, Joski PJ, Galactionova E. Infant delivery costs related to maternal smoking: an update. Nicotine Tob Res. 2011;13(8):627-37.

CDC. PRAMS and smoking. http://www.cdc.gov/prams/TobaccoandPrams.htm. Accessed September 6, 2012.

Dietz PM, England LJ, Shapiro-Mendoza CK, Tong VT, Farr SL, Callaghan WM. Infant morbidity and mortality attributable to prenatal smoking in the U.S. Am J Prev Med. 2010;39(1):45-52.

Heil SH, Higgins ST, Bernstein IM, Solomon LJ, Rogers RE, Thomas CS, Badger GJ, Lynch ME. Effects of voucher-based incentives on abstinence from cigarette smoking and fetal growth among pregnant women. Addiction. 2008 Jun;103(6):1009-18.

Higgins ST, Washio Y, Heil SH, Solomon LJ, Gaalema DE, Higgins TM, Bernstein IM. Financial incentives for smoking cessation among pregnant and newly postpartum women. Prev Med. 2011 Dec 27.

Higgins ST, Bernstein IM, Washio Y, Heil SH, Badger GJ, Skelly JM, Higgins TM, Solomon LJ. Effects of smoking cessation with voucher-based contingency management on birth outcomes.Addiction. 2010 Nov;105(11):2023-30 Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD001055. Review.

SRNT Subcommittee on Biochemical Verification. Biochemical verification of tobacco use and cessation. Nicotine Tob Res. 2002 May;4(2):149-59.

Tong VT, Jones JR, Dietz PM, D'Angelo D, Bombard JM; Centers for Disease Control and Prevention (CDC). Trends in smoking before, during, and after pregnancy - Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 31 sites, 2000-2005. MMWR Surveill Summ. 2009 May 29;58(4):1-29.

Section II. Award Information

Funds Available and Anticipated Number of Awards

NCCDPHP intends to commit approximately $560,000 (including both direct and indirect costs) in FY2013 to fund one (1) applicant for the first 12-month budget period.

An applicant may request a project period of up to five (5) years. The funding amount may be up to $560,000 (including direct and indirect costs) each year for the 2nd, 3rd, 4th, and 5th years of the project.

The estimated total funding (direct and indirect) for the entire five (5) year project period is $2,800,000.

If an applicant requests a funding amount greater than the ceiling of the award range for the first year ($560,000), HHS/CDC will consider the application non-responsive, and it will not enter into the review process. HHS/CDC will notify the applicant that the application did not meet the submission requirements.

There is no floor (minimum amount to be awarded) for this award.

Throughout the project period, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (http://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html) will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information Eligible Applicants

Eligible Organizations Higher Education Institutions:

· Public/State Controlled Institutions of Higher Education

· Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for CDC support as Public or Private Institutions of Higher Education:

· Hispanic-serving Institutions

· Historically Black Colleges and Universities (HBCUs)

· Tribally Controlled Colleges and Universities (TCCUs)

· Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education Nonprofits (Other than Institutions of Higher Education)

For- Profit Organizations Small Businesses For-Profit Organizations (Other than Small Businesses)

Governments State Governments County Governments City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession

Other Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American tribal organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Regional Organizations

· Bona Fide Agents: a Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms" when submitting via www.grants.gov.

· Federally Funded Research and Development Centers (FFRDCs): FFRDCs are operated, managed, and/or administered by a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm, as an autonomous organization or as an identifiable separate operating unit of a parent organization. A FFRDC meets some special long-term research or development need which cannot be met as effectively by an agency’s existing in-house or contractor resources. FFRDC's enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. For more information on FFRDCs, go to http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=512ff78311f427c00454772dcf21523a&rgn=div8&view=text&node=48:1.0.1.6.34.0.1.18&idno=48.

· Other: None

2. Foreign Organizations Foreign Organizations are not eligible to apply.

Foreign components of U.S. Organizations are not eligible to apply.

For this announcement, applicants may not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Special Eligibility Requirements:

Eligible applicants must have evidence of an established relationship with one or more study sites that meet the criteria:

a. Must provide evidence, in the form of reports, letters or written agreements with study sites that report the number and percentage of pregnant smokers attending prenatal health services annually from each site where women will be recruited and enrolled into the study. The study population must include economically disadvantaged women as defined by at least 25% of the pregnant smoking women attending the prenatal clinics from the sites be Medicaid-insured pregnant women who continued smoking during pregnancy. Each clinic where subjects are recruited must have a smoking rate of at least 10% among pregnant women.

b. Must provide evidence, in the form of a letter, of having access to and the ability to collect reimbursed medical costs for all related services. Must provide evidence of permission to access the medical cost data and how this data will be collected.

c. Must provide evidence that the PI for the proposed RCT previously has been the principal investigator or co-principal investigator on at least one contingency management RCT among pregnant women for smoking cessation during pregnancy. That evidence must include the reference and abstract of one first-author publication in a peer-reviewed journal.

d. Must provide evidence that the research team includes an economist with experience in cost-benefit research of interest. Must provide evidence of publications, references, and abstracts of relevant publications by the economist addressing the cost-benefit of an intervention.

4. Justification for Less than Maximum Competition: - None

5. Responsiveness:

Evidence for the special eligibility criteria listed in number 3, a-d above must be presented in Appendix A of the application. If your application is incomplete or non-responsive to these requirements, it will not enter into the review process.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, http://www.grants.gov/applicants/org_step2.jsp.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

7. Universal Identifier Requirements and Central Contractor Registration All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM), the replacement system for the Central Contractor Registration (CCR) database. Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the grantee organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its DUNS number to the grantee organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for HHS/CDC support.

9. Cost Sharing This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html).

10. Number of Applications Only one application per institution (normally identified by having a unique DUNS number) is allowed.

As defined in the HHS Grants Policy Statement, (http://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html), applications received in response to the same funding opportunity announcement generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Section IV. Application and Submission Information

1. Address to Request Application Package Applicants must download the SF424 (R&R) application package associated with this funding opportunity from www.Grants.gov.

If access to the Internet is not available or if the applicant encounters difficulty accessing the forms on-line, contact the HHS/CDC Procurement and Grants Office Technical Information Management Section (PGO TIMS) staff at (770) 488-2700 or pgotim@cdc.gov for further instructions. Hours: Monday - Friday, 7am – 4:30pm U.S. Eastern Standard Time. CDC Telecommunications for the hearing impaired or disabled is available at: TTY 1-888-232-6348.

Content and Form of Application Submission It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/guide/url_redirect.htm?id=12000), except where instructed in this Funding Opportunity Announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow the instructions in the SF 424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application. While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components. These forms can be downloaded and uploaded as Attachment A from the following link: http://www.cdc.gov/od/pgo/funding/grants/foamain.shtm

Letter of Intent Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows CIO staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Name of the Applicant Descriptive title of proposed research Name, address, and telephone number of the PD(s)/PI(s) Names of other key personnel Participating institutions Number and title of this funding opportunity

The letter of intent should be sent to:

Michael A. Brown, M.P.H.

Scientific Program Official Extramural Research Program Office Centers for Disease Control and Prevention 4770 Buford Hwy, NE Mailstop F-46 Atlanta, GA 30341 Telephone: (770) 488-5118

FAX: (770) 488-7863

E-mail: mab5@cdc.gov

Required and Optional Components A complete application has many components, both required and optional. The forms package associated with this FOA in Grants.gov includes all applicable components for this FOA, required and optional.

PHS 398 Research Plan Component The SF424 (R&R) Application Guide includes instructions for applicants to complete a PHS 398 Research Plan that consists of 16 components. Not all 16 components of the Research Plan apply to all Funding Opportunity Announcements (FOAs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See Part I, Section 5.5 of the SF 424 (R&R) Application Guide (http://grants.nih.gov/grants/guide/url_redirect.htm?id=12000) for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Funding Opportunity Announcement Description). Follow the page limits stated in the SF 424 unless otherwise specified in the FOA. As applicable to and specified in the FOA, the application should include the bolded headers in this section and should address activities to be conducted over the course of the entire project, including but not limited to:

1. Introduction to Application (for Resubmission and Revision ONLY) - provide a clear description about the purpose of the proposed research and how it addresses the specific requirements of the FOA.

2. Specific Aims – state the problem the proposed research addresses and how it will result in public health impact and improvements in population health.

3. Research Strategy – the research strategy should be organized under 3 headings: Significance, Innovation and Approach. Describe the proposed research plan, including staffing and timeline.

4. Inclusion Enrollment Report (Renewal and Revision applications ONLY)

5. Progress Report Publication List (for Continuation ONLY)

Human Subjects Section

6. Protection of Human Subjects

7. Inclusion of Women and Minorities

8. Targeted/Planned Enrollment Table (for New Application ONLY)

9. Inclusion of Children

Other Research Plan Sections

10. Vertebrate Animals

11. Select Agent Research

12. Multiple PD/PI Leadership Plan.

13. Consortium/Contractual Arrangements

14. Letters of Support

15. Resource Sharing Plan(s)

16. Appendix

Component 4 (Inclusion Enrollment Report) applies only to Renewal and Revision applications for clinical research. Clinical research is that which is conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies). Follow the page limits in the SF 424 unless otherwise specified in the FOA.

All instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerB.pdf) must be followed along with any additional instructions provided in the FOA.

The research plan should address activities to be conducted over the entire project period and must include the following:

Introduction/Background

· Describe the demographics (e.g., age, race/ethnicity, income, insurance status) of the pregnant clients served by the site(s) where the intervention will be implemented and evaluated. Include rates of smoking during pregnancy, and rates of fetal growth restriction and preterm birth.

· Describe the site(s) from which pregnant smokers will be recruited. Include prenatal health services provided to the target population at the proposed site(s), including (but not limited to) smoking cessation services offered during prenatal care either on-site, by referral, or available in the surrounding community. Include any clinic protocols specific to smoking assessment and cessation services.

· Describe the research team’s experience developing and evaluating RCTs to evaluate contingency management interventions aimed at increasing smoking cessation during pregnancy. Include information on experience with RCTs for evaluating the cost-benefit of interventions.

· Describe the research team’s experience collecting medical cost reimbursement information and analyzing medical claims data.

· Describe the research team’s experience working with the target population within the site(s) where the intervention will be implemented and evaluated, including experience of proposed staff.

· Demonstrate capacity to recruit the estimated number of prenatal smokers required for an adequately powered 3-arm RCT.

· Describe experience retaining pregnant smokers, from the target population, in longitudinal studies. Include steps taken to locate participants that are lost to follow-up.

· Provide letter(s) of support from proposed site(s). In addition to a commitment to collaborate, the letter of support should identify proposed roles for site staff.

Specific Aims

· Specify overall aims or objectives for intervention development and evaluation.

· Specify primary and secondary outcomes, how they will be measured, and expected effect size.

Research strategy

· Describe the RCT to increase smoking cessation among pregnant women and each of the 3 arms: 1) a high intensity CM intervention arm; 2) a low intensity CM intervention arm; and 3) a standard of care arm.

· Describe the inclusion criteria of study participants.

· Describe how the proposed intervention approaches or methodologies will be integrated into ongoing services at the proposed site(s).

· Describe whether and how the proposed intervention will appeal to the target population, and how it will be culturally appropriate, including incentives that will be used in the high and low intensity contingency management study arms.

· Provide information on sample size calculations for the RCT. The RCT should be powered with respect to the primary outcomes (bio-chemically confirmed quit by end of pregnancy and cost-benefit) and must take into account the unit of randomization (e.g., individual, group).

· Describe approach for recruitment and retention of the study participants.

· Describe approach for randomization of study participants or sites, depending on the unit of analysis, into the 3 arms.

· Describe method of data collection, management and quality assurance.

· Describe how abstinence from smoking will be biochemically verified. It is required that abstinence from smoking be biochemically verified.

· Provide a timeline for conducting follow-up assessments and collecting biological and behavioral data at baseline and subsequent time points during a minimum follow-up period of 6 months after delivery.

· Describe how study data will be analyzed to compare abstinence at end of pregnancy and cost–benefit of the interventions using appropriate statistical methods.

· Describe plans to share de-identified data with CDC for secondary analyses.

· Describe expected changes in biological and behavioral outcomes associated with the proposed intervention (e.g., specify baseline and post-intervention rates of smoking).

· Describe expected contributions to the field (e.g., further understanding of CM interventions for pregnant smokers, potential for dissemination to and sustainability of the proposed intervention in the health care system).

Staffing and Milestones for Development and Implementation Phases

· Describe experience and expertise of key proposed staff, including ability to conduct a RCT using contingency management to increase smoking cessation among pregnant smokers and the ability to evaluate cost-benefit of different interventions in a 3-arm RCT.

· Identify tasks and a timeline for key intervention and protocol development activities to occur in the first 18 months of the project (i.e., development phase and first 6 months of intervention implementation phase). Include milestones and/or measurable outputs that will be used to indicate progress toward having an Institutional Review Board (IRB)-approved protocol and all intervention materials pilot-tested, revised, and intervention staff trained within the first 18 months of the project.

· Identify key milestones and staffing needs for implementation of the RCT and cost-benefit evaluation (e.g., recruitment and enrollment, intervention delivery, data collection, data management, data analysis, report writing).

· Provide evidence of a clear management and staffing plan for all 3 phases: 1) Development; 2) Intervention implementation; and 3) Study findings, publications and dissemination.

· Include in the budget planned travel each year for two key staff to attend an annual meeting in Atlanta, GA to discuss study progress and any issues related to accomplishing project objectives.

Appendix Do not use the appendix to circumvent page limits. A maximum of 10 PDF documents are allowed in the appendix.