TESTING TOBACCO PRODUCTS PROMOTED TO REDUCE HARM

RELEASE DATE:  May 5, 2004

PA NUMBER:  PA-04-103

The R01 portion of this funding opportunity has been 
replaced by PA-07-174, which now uses the electronic SF424 (R&R) 
application for February 5, 2007 submission dates and beyond.

March 2, 2006 (NOT-OD-06-046)   Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
expires on the date indicated below. Other mechanisms relating to this announcement 
will continue to be accepted using paper PHS 398 applications until the stated 
expiration date below, or transition to electronic application submission. 
A replacement R21 (PA-06-361) funding opportunity announcement has been issued 
for the submission date of June 1, 2006 and submission dates for AIDS and 
non-AIDS applications thereafter.

EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006 
EXPIRATION DATE for All R01 Applications: November 2, 2006

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Cancer Institute (NCI) 
 (http://www.nci.nih.gov/)
National Institute on Drug Abuse (NIDA) 
 (http://www.nida.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.393, 93.399, 93.279

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanisms of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Receipt and Review Schedule
o Required Federal Citations

PURPOSE OF THIS PA

The purpose of this Program Announcement (PA) is to stimulate 
multidisciplinary research on potential reduced-exposure tobacco products, 
both smoked and smokeless, through the interplay of basic, biological, and 
behavioral research, surveillance, and epidemiology. The tobacco industry is 
currently promoting some new products with claims that they are less harmful 
or less addictive because these products purportedly deliver lower amounts of 
toxic, carcinogenic, and/or addictive agents to the user compared with 
conventional products. However, to date, the scientific evidence is 
insufficient to evaluate whether these new products actually reduce the 
users  exposure or risk for tobacco-related diseases. The key research 
question of this PA is,  Do potential reduced-exposure tobacco products 
provide a truly, less-harmful alternative to conventional tobacco products, 
both on the individual and population level? 

RESEARCH OBJECTIVES

The objective of this Program Announcement (PA) is to stimulate 
multidisciplinary research on the chemical composition, behavior of use, 
exposure to toxic agents, addictive properties, differential toxicity, and 
individual and public health impact of potential reduced-exposure tobacco 
products. 

Forty years after the Surgeon General’s first report on smoking and health, 
tobacco use continues to pose an enormous public health threat in the United 
States and worldwide. In 2000, 46 million people in the United States (23.3 
percent of the adult population 18 years of age or older) were smokers and 
44.3 million adults (22.2 percent) were former smokers (CDC, 2002). During 
the period 1995-1999, more than 440,000 people died annually from smoking-
attributable diseases. 

Current smoking prevalence among U.S. adults is nearly double the nation’s 
year 2010 health goal of 12 percent (Objective 27-1a, Healthy People 2010).  
Current low annual quit rates (4.7 percent of current smokers quit and 
maintained abstinence for 3-12 months in 2000; CDC, 2002) and high relapse 
rates among those who have tried to quit (60-90 percent after one year off; 
CDC MMWR, July 2003) present strong challenges to meeting the 2010 goal. 

Currently, there is increased interest among public health scientists in 
evaluating potential strategies to reduce the harm among people who continue 
tobacco use (Stratton et. al., 2001). However, previous tobacco harm 
reduction efforts pursued by the public health community were limited by 
incomplete knowledge and methods for evaluating the health impact of modified 
tobacco products. In the late 1960s, the Federal Trade Commission (FTC) 
established a laboratory to measure and report on the levels of tar and 
nicotine in mainstream smoke of cigarettes by brand (National Cancer 
Institute, 1996).  Based on the FTC protocol, the average sales-weighted tar 
and nicotine smoke yields have decreased by about 70 percent since the 1950s 
(Hoffmann and Hoffmann, 2001). Yet a recent NCI review of the risks 
associated with smoking cigarettes with low, machine-measured yields of tar 
and nicotine demonstrated that  there is no convincing evidence that changes 
in cigarette design between the1950s and the 1980s have resulted in an 
important decrease in the disease burden caused by cigarette use either for 
smokers as a group or for the whole population  (Burns et al., 2001). 

The theoretical benefits of low-yield products were offset by the fact that 
these products were designed to allow compensatory smoking behaviors so that 
smokers could overcome draw resistance and obtain the desired dose of 
nicotine (Burns et al., 2001) More intense puffing on ventilated, low-yield 
products may have resulted in an increase in delivered dosages of cancer-
causing agents as well as nicotine to the smoker (Djordjevic et al., 2000). 
In addition to failing to reduce cancer risk, low-yield cigarettes may have 
played a significant role in promoting initiation and impeding cessation, the 
most important determinants of smoking-related diseases (Burns and Benowitz, 
2001).

In recent years, there has been a proliferation of new potential reduced-
exposure tobacco products that are marketed and advertised by the tobacco 
industry, with claims that they are less harmful or less addictive compared 
with conventional tobacco products. These products have specifically 
targeted: (a) current tobacco users who are as yet unable or unwilling to 
quit; (b) health-conscious individuals who perceive switching to a 
potentially less hazardous product as beneficial and more appealing than 
trying to quit; and (c) smokers who want an alternative to cigarettes when 
they are in smoke-free environments (e.g., workplace, home, during travel). 

Many of these products have not yet been widely used in larger populations. 
Their toxicity is generally unknown, and their potential impact on both 
individual and public health is also unknown. The limited scientific evidence 
currently available, based on a handful of small studies, is inconsistent and 
insufficient for developing meaningful conclusions about whether there is any 
reduction in harm to tobacco users who switch to these products. Some small, 
short-term clinical studies have suggested that smokers who switch to 
potential reduced-exposure products have lower levels of biomarkers for known 
carcinogens, including the lung-specific carcinogen 4-(methylnitrosamino)-1-
(3-pyridyl)-1-butanone (NNK) and polynuclear aromatic hydrocarbons (PAHs) 
(Breland et al., 2003, Melikian et al., 2003). However, other clinical 
studies have suggested that such products are unlikely to significantly 
reduce smokers  exposure to harmful tobacco smoke constituents (Breland et 
al., 2002, Lemmonds et al., 2003). Moreover, the design of some products may 
use ingredients or materials that pose additional health risks  (Pauly et 
al., 1998), and smokers who switch to such products may smoke more often or 
more intensely to compensate for reduced nicotine delivery  (Buchhalter and 
Eisenberg, 2000).  

Even if potential reduced-exposure products are shown to be less toxic to the 
individual, their impact must also be evaluated at the population level. The 
introduction and marketing of these new products might results in a reduction 
in quitting rates, an increase in initiation and progression of tobacco use 
by youth and young adults, and/or a secondary initiation by former smokers.. 
For example, a recent study found that young males who were not smokers in 
1989 but regularly used smokeless tobacco were more than three times as 
likely as never users to be current smokers 4 years later (Tomar, 2003). 
Moreover, it is possible that smokers of conventional cigarettes will not 
completely switch to new products, but will continue using multiple products 
to obtain desired doses of nicotine. There are also questions regarding harm 
to nonsmokers who are exposed to secondhand smoke. Although there is a clear 
reduction in environmental tobacco smoke from using smokeless tobacco or 
cigarettes that heat rather than burn tobacco, there may be an increase in 
secondhand smoke exposure if smoking duration or prevalence increases or if 
new products result in an increase in toxicants present in either sidestream 
smoke or exhaled mainstream smoke.

Applications to study potential reduced-exposure tobacco products and their 
potential public health impact are encouraged in, though not limited to, the 
following areas:

o  studying behavioral changes that accompany use of new smoked and smokeless 
tobacco products that are being marketed with health claims and how these 
behaviors, including possible dual use with other products, impact delivered 
dosages of addictive agents and toxins, including carcinogens;

o  validating currently available tobacco exposure and candidate disease-
specific surrogate biomarkers;

o  developing new biomarkers that accurately reflect mechanisms of disease to 
serve as intermediate indicators of disease and disease risk; 

o  exploring differential toxicity of various tobacco and nicotine products 
using in vitro and in vivo models;

o  examining the relationship between a reduction in tobacco toxins and 
health and biomarker endpoints;

o  developing comprehensive surveillance systems to monitor marketing, 
patterns of use, and health consequences of new potential reduced-exposure 
tobacco products; and/or

o  examining the impact of marketing on consumers' and healthcare providers' 
attitudes, knowledge, and perceptions about new products, and exploring ways 
to communicate accurate information about these products. 

Additional research questions and priorities related to purported reduced-
exposure tobacco products have been identified elsewhere (Stratton et. al. 
2001, Hatsukami et al. 2002).

MECHANISMS OF SUPPORT 

This PA will use the NIH investigator-initiated research project grant (R01) 
and the exploratory/developmental grant (R21) award mechanisms.  As an 
applicant, you will be solely responsible for planning, directing, and 
executing the proposed project. 

For R01 applications submitted in response to this PA, the total proposed 
project period may not exceed 5 years.  

For R21 submissions, the applicant may request a project period of up to 2 
years with a combined budget for direct costs of up $275,000 for the 2-year 
period.  For example, the applicant may request $100,000 in the first year and 
$175,000 in the second year.  The request should be tailored to the needs of 
the project.  Normally, no more than $200,000 may be requested in a single 
year.

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular budget format.  Otherwise, follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.  

ELIGIBLE INSTITUTIONS 

You may submit (an) application(s) if your institution has any of the 
following characteristics:
   
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government 
o Domestic or foreign institutions/organizations
o Faith-based or community-based organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution 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 NIH programs.  

SPECIAL REQUIREMENTS
 
Investigators will be convened twice annually throughout the award period to 
discuss research findings and methods with other grantees. Support for travel 
by the Principal Investigator and one co-investigator should be included in 
the proposed budget.  For purposes of estimating budgets, plan on two 2-day 
meetings each year, with one meeting on the East Coast of the United States 
and one on the West Coast. 

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

o Direct your questions about scientific/research issues to:

Mirjana V. Djordjevic, Ph.D.
Division for Cancer Control and Population Sciences 
National Cancer Institute 
6120 Executive Boulevard, EPN Room 4044, MSC 7337
Bethesda, MD  20892
Rockville, MD 20852 (for courier/express service)
Telephone:  (301) 496-8584 
FAX:  (301) 496-8675
Email: djordjev@mail.nih.gov

Allison L. Chausmer, Ph.D.
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD 20892
Rockville MD 20852 (for courier/express service)
Telephone: (301) 402-5088
FAX: (301) 594-6043
Email: achausme@nida.nih.gov

o Direct your questions about financial or grants management matters to:

Ms. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243, MSC 7150
Bethesda, MD 20892-7150
Rockville, MD 20852 (express/courier service)
Telephone:  301-496-8634
Fax:  301-496-8601
Email: wolfreyc@mail.nih.gov

Gary Fleming, J.D.
National Institute on Drug Abuse
6101 Executive Boulevard, Room 250, MSC 8403
Bethesda, MD  20892-9605
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-6710
FAX:  (301) 594-6849
Email:  gfleming@nida.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have 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 can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance, contact GrantsInfo; Telephone: (301) 710-0267; Email: GrantsInfo@nih.gov.

The title and number of this program announcement must be typed on line 2 of 
the face page of the application form and the YES box must be checked.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: 
 
Applications requesting up to $250,000 per year in direct costs must be 
submitted in a modular grant format.  The modular grant format simplifies the 
preparation of the budget in these applications by limiting the level of 
budgetary detail.  Applicants request direct costs in $25,000 modules.  
Section C of the research grant application instructions for the PHS 398 
(rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html 
includes step-by-step guidance for preparing modular grants.  Additional 
information on modular grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:  
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:
   
1) Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your         
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member       
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt 
dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm.  The CSR will 
not accept any application in response to this PA that is essentially the 
same as one currently pending initial review unless the applicant withdraws 
the pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an unfunded version of an application 
already reviewed, but such application must include an Introduction 
addressing the previous critique.  

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.   Appropriate scientific review groups 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate national advisory council 
or board. 

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of these criteria in assigning the 
application’s overall score, weighting them as appropriate for each 
application.  

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

SIGNIFICANCE: Does this study address an important problem? If the aims of 
the application are achieved, how will scientific knowledge be advanced? What 
will be the effect of these studies on the concepts or methods that drive 
this field?

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

INNOVATION: Does the project employ novel concepts, approaches or methods? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

INVESTIGATOR: Is the investigator appropriately trained and well suited to 
carry out this work? Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below.)
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below.)

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS 

Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers. However, 
reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score.  
(http://grants.nih.gov/grants/policy/data_sharing )

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities 
involving live, vertebrate animals must comply with PHS Policy on Humane Care 
and Use of Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as 
mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA 
Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
See http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm. 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); and efficacy, 
effectiveness, and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants. (See NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998, at 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html.) 

Clinical trials supported or performed by NCI require special considerations.  
The method and degree of monitoring should be commensurate with the degree of 
risk involved in participation and the size and complexity of the clinical 
trial.  Monitoring exists on a continuum from monitoring by the principal 
investigator/project manager or NCI program staff or a Data and Safety 
Monitoring Board (DSMB).  These monitoring activities are distinct from the 
requirement for study review and approval by an Institutional review Board 
(IRB).  For details about the Policy for the NCI for Data and Safety 
Monitoring of Clinical trials, see 
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.  For Phase I and II 
clinical trials, investigators must submit a general description of the data 
and safety monitoring plan as part of the research application.  For 
additional information, see NIH Guide Notice on  Further Guidance on a Data 
and Safety Monitoring for Phase I and II Trials  at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.  
Information concerning essential elements of data safety monitoring plans for 
clinical trials funded by the NCI is available at 
http://www.cancer.gov/clinical_trials/.

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking 
$500,000 or more in direct costs in any single year are expected to include a 
plan for data sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing . Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: (a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and (b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. 

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.  A 
continuing education program in the protection of human participants in 
research is available online at http://cme.nci.nih.gov/.
 
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the  Standards for Privacy of Individually Identifiable Health Information,  
the  Privacy Rule,  on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on  Am I a covered 
entity?   Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.

References

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Breland, A.B., Acosta, M.C., and Eissenberg, T. (2003) Tobacco-specific 
nitrosamines and potential reduced exposure products for smokers: A 
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Buchhalter, A.R. and Eissenberg, T. (2000) Preliminary evaluation of a novel 
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Burns, D.M. and Benowitz, N.L. (2001) Public health implications of changes 
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Burns, D.M., Major, J.M., Shanks, T.G., Thun, M.J., and Samet, J.  (2001) 
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Djordjevic, M. V., Stellman, S. D., Zang, E. (2000). Doses of Nicotine and 
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Varga, J.H. Jaffe, W. H. Barr (2003) Reduction of Urinary Metabolites of 
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Pauly, J.L., Allart, H.A., Rodrigez, M.I., and Streck, R.J. (1995) Fibers 
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Tomar, S. (2003) Is use of smokeless tobacco a risk factor for cigarette 
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