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[Federal Register Volume 79, Number 124 (Friday, June 27, 2014)]
[Notices]
[Pages 36514-36516]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-14962]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality

Scientific Information Request on Interventions To Improve 
Appropriate Antibiotic Use for Acute Respiratory Tract Infections

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for Scientific Information Submissions.

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public. Scientific 
information is being solicited to inform our review of Interventions to 
Improve Appropriate Antibiotic Use for Acute Respiratory Tract 
Infections, which is currently being conducted by the Evidence-based 
Practice Centers for the AHRQ Effective Health Care Program. Access to 
published and unpublished pertinent scientific information will improve 
the quality of this review. AHRQ is conducting this systematic review 
pursuant to Section 1013 of the Medicare Prescription Drug, 
Improvement, and Modernization Act of 2003, Public Law 108-173, and 
Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a).

DATES: Submission Deadline on or before July 28, 2014.

ADDRESS: Online submissions: http://effectivehealthcare.AHRQ.gov/index.cfm/submit-scientific-information-packets/. Please select the 
study for which you are submitting information from the list to upload 
your documents. Email submissions: /src.org">src.org">SIPS@epc-src.org.

Print Submissions

Mailing Address

    Portland VA Research Foundation, Scientific Resource Center, ATTN: 
Scientific Information Packet Coordinator, PO Box 69539, Portland, OR 
97239.

Shipping Address (FedEx, UPS, etc.)

    Portland VA Research Foundation, Scientific Resource Center, ATTN: 
Scientific Information Packet Coordinator, 3710 SW. U.S. Veterans 
Hospital Road, Mail Code: R&D 71, Portland, OR 97239.

FOR FURTHER INFORMATION CONTACT: Ryan McKenna, Telephone: 503-220-8262 
ext. 58653 or Email: /src.org">src.org">SIPS@epc-src.org.

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Effective Health Care (EHC) Program 
Evidence-based Practice Centers to complete a review of the evidence 
for Interventions to Improve Appropriate Antibiotic Use for Acute 
Respiratory Tract Infections.
    The EHC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on Interventions to Improve Appropriate Antibiotic Use for 
Acute Respiratory Tract Infections, including those that describe 
adverse events. The entire research protocol, including the key 
questions, is also available online at: http://effectivehealthcare.AHRQ.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1913.
    This notice is to notify the public that the EHC Program would find 
the following information on Interventions to Improve Appropriate 
Antibiotic Use for Acute Respiratory Tract Infections helpful:
     A list of completed studies that your company has 
sponsored for this indication. In the list, indicate whether results 
are available on ClinicalTrials.gov along with the ClinicalTrials.gov 
trial number.
     For completed studies that do not have results on 
ClinicalTrials.gov, please provide a summary, including the following 
elements: study number, study period, design, methodology, indication 
and diagnosis, proper use instructions, inclusion and exclusion 
criteria, primary and secondary outcomes, baseline characteristics, 
number of patients screened/eligible/enrolled/lost to follow-up/
withdrawn/analyzed, effectiveness/efficacy, and safety results.
     A list of ongoing studies your company has sponsored for 
this indication. In the list, please provide the ClinicalTrials.gov 
trial number or, if the trial is not registered, the protocol for the 
study including a study number, the study period, design, methodology, 
indication and diagnosis, proper use instructions, inclusion and 
exclusion criteria, and primary and secondary outcomes.

[[Page 36515]]

     Description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your company for this 
indication and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the EHC Program. Since the 
contents of all submissions will be made available to the public upon 
request, materials submitted must be publicly available or can be made 
public. Materials that are considered confidential; marketing 
materials; study types not included in the review; or information on 
indications not included in the review cannot be used by the EHC 
Program. This is a voluntary request for information, and all costs for 
complying with this request must be borne by the submitter.
    The draft of this review will be posted on AHRQ's EHC Program Web 
site and available for public comment for a period of 4 weeks. If you 
would like to be notified when the draft is posted, please sign up for 
the email list at: http://effectivehealthcare.AHRQ.gov/index.cfm/join-the-email-list1/.
    The systematic review will answer the following questions. This 
information is provided as background. AHRQ is not requesting that the 
public provide answers to these questions. The entire research protocol 
is also available online at: http://effectivehealthcare.AHRQ.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1913.

The Key Questions

Key Question 1

    For patients with an acute respiratory tract infection (RTI) and no 
clear indication for antibiotic treatment, what is the comparative 
effectiveness of particular strategies in improving the appropriate 
prescription or use of antibiotics compared with other strategies or 
standard care?
    I. Does the comparative effectiveness of strategies differ 
according to how appropriateness is defined?
    II. Does the comparative effectiveness of strategies differ 
according to the intended target of the strategy (i.e., clinicians, 
patients, and both)?
    III. Does the comparative effectiveness of strategies differ 
according to patient characteristics, such as type of Rh, signs and 
symptoms (nature and duration), when counting began for duration of 
symptoms, previous medical history (e.g., frailty, comorbidity), prior 
RTIs, and prior use of antibiotics, age, ethnicity, socioeconomic 
status, and educational level attained?
    IV. Does the comparative effectiveness of strategies differ 
according to clinician characteristics, such as specialty, number of 
years in practice, type of clinic organization, geographic region, and 
population served?
    V. Does the comparative effectiveness differ according to the 
diagnostic method or definition used, the clinician's perception of the 
patient's illness severity, or the clinician's diagnostic certainty?
    VI. Does the comparative effectiveness differ according to various 
background contextual factors, such as the time of year, known patterns 
of disease activity (e.g., an influenza epidemic, a pertussis 
outbreak), system-level characteristics, or whether the intervention 
was locally tailored?

Key Question 2

    For patients with an acute RTI and no clear indication for 
antibiotic treatment, what is the comparative effect of particular 
strategies on antibiotic resistance and medical complications 
(including mortality and adverse effects of receiving or not receiving 
antibiotics) compared with other strategies or standard care?
    I. Does the comparative effect of strategies differ according to 
the intended target of the strategy (i.e., clinicians, patients, and 
both)?
    II. Does the comparative effect of strategies differ according to 
patient characteristics, such as type of RTI, signs and symptoms 
(nature and duration), when counting began for duration of symptoms, 
previous medical history (e.g., frailty, comorbidity), prior RTIs, 
prior use of antibiotics, age, ethnicity, socioeconomic status, and 
educational level attained?
    III. Does the comparative effect of strategies differ according to 
clinician characteristics, such as specialty, number of years in 
practice, type of clinic organization, geographic region, and 
population served?
    IV. Does the comparative effectiveness differ according to the 
diagnostic method or definition used, the clinician's perception of the 
patient's illness severity, or the clinician's diagnostic certainty?
    V. Does the comparative effect differ according to various 
background contextual factors, such as the time of year, known patterns 
of disease activity (e.g., an influenza epidemic, a pertussis 
outbreak), whether the intervention was locally tailored, system-level 
characteristics, or the source of the resistance data (i.e., population 
versus study sample)?

Key Question 3

    For patients with an acute RTI and no clear indication for 
antibiotic treatment, what is the comparative effect of particular 
strategies on other clinical outcomes (e.g., hospitalization, health 
care utilization, patient satisfaction) compared with other strategies 
or standard care?
    I. Does the comparative effect of strategies differ according to 
the intended target of the strategy (i.e., clinicians, patients, and 
both)?
    II. Does the comparative effect of strategies differ according to 
patient characteristics, such as type of RTI, signs and symptoms 
(nature and duration), when counting began for duration of symptoms, 
previous medical history (e.g., frailty, comorbidity), prior RTIs, 
prior use of antibiotics, age, ethnicity, socioeconomic status, and 
educational level attained?
    III. Does the comparative effect of strategies differ according to 
clinician characteristics, such as specialty, number of years in 
practice, type of clinic organization, geographic region, and 
population served?
    IV. Does the comparative effectiveness differ according to the 
diagnostic method or definition used, the clinician's perception of the 
patient's illness severity, or the clinician's diagnostic certainty?
    V. Does the comparative effect differ according to various 
background contextual factors, such as the time of year, known patterns 
of disease activity (e.g., an influenza epidemic, a pertussis 
outbreak), whether the intervention was locally tailored or system-
level characteristics?

Key Question 4

    For patients with an acute Rh I and no clear indication for 
antibiotic treatment, what is the comparative effect of particular 
strategies on achieving intended intermediate outcomes, such as 
improved knowledge regarding use of antibiotics for acute RTIs 
(clinicians and/or patients), improved shared decision making regarding 
the use of antibiotics, and improved clinician skills for appropriate 
antibiotic use (e.g., communication appropriate for patients' literacy 
level and/or cultural background)?

Key Question 5

    What are the comparative non-clinical adverse effects of strategies 
for improving the appropriate use of antibiotics for acute RTIs (e.g., 
increased time burden on clinicians, patients, clinic staff)?
    The following inclusion/exclusion criteria reflect input from key 
informants, public comments, AHRQ and the TEP.

[[Page 36516]]

PICOTS (Population, Interventions, Comparators, Outcomes, Timing, 
Setting)

Populations

    I. Adult and pediatric patients with an acute RTI and no clear 
indication for antibiotic treatment. Respiratory tract infections of 
interest include: acute bronchitis; otitis media; sore throat/
pharyngitis/tonsillitis; rhinitis; sinusitis; cough and common cold.
    II. Parents of pediatric patients with acute RTI and no clear 
indication for antibiotic treatment.
    III. Healthy adults and/or children without a current acute RTI, 
who may develop an acute RTI in the future.
    IV. Clinicians and others who care for patients with acute RTI in 
outpatient settings.
    V. Groups whose attendance policies may indirectly affect the use 
of antibiotics, such as employers or school officials.

Interventions

    Any strategy for improving appropriate use of antibiotics when not 
indicated for acute RTI, which may fall into various categories, 
including:
    I. Educational, behavioral and psychological interventions that 
target clinicians, patients, or both.
    II. Strategies to improve communication between clinicians and 
patients, such as those designed to improve shared decision making.
    III. Clinical strategies, such as delayed prescribing of 
antibiotics, clinical prediction rules, use of risk assessment or 
diagnostic prediction, use of non-antibiotic alternatives, or use of 
relevant point-of-care (POC) diagnostic tests.
    A. EPC will include any POC test that is available and used in 
primary care settings for diagnostic purposes with the ability to 
provide results within a reasonable period (e.g. during the clinic 
visit). Examples include inflammatory tests (e.g., procalcitonin, c-
reactive protein [CRP], white blood cell, etc.), rapid multiplex 
polymerase chain reaction (PCR) tests used to rule in/out organisms 
(e.g. rapid strep test, influenza, RSV), routine diagnostic tests, such 
as chest x-ray, pulse oximetry, and blood gasses, when they are 
specifically evaluated as an intervention for improving antibiotic use.
    IV. System level strategies, such as clinician reminders (paper-
based or electronic), clinician audit and feedback, financial or 
regulatory incentives for clinicians or patients, antimicrobial 
stewardship programs, pharmacist review.
    V. Multifaceted approaches that include numerous elements of one or 
more of the above strategies.

Comparators

    I. Different strategies for improving appropriate use of 
antibiotics when not indicated for acute RTI.
    II. Standard care without a strategy for improving appropriate use 
of antibiotics.

Outcomes

Key Question 1

 Increased appropriate prescription of antibiotics (primary 
outcome)
 Increased appropriate use of antibiotics (primary outcome)

    Note: Studies may vary in how appropriateness is defined or 
determined. We will accept and record any definition of 
appropriateness. We will group together studies that use similar 
definitions of appropriateness and categorize the different groups 
based on concordance with (e.g., high, medium, low) select clinical 
practice guidelines (e.g., AAP, ACCP, AAFP). We will then evaluate 
whether the comparative effectiveness of strategies differ across 
categories. We may also find that overall reduction in antibiotic 
prescription or use is reported, without a determination of 
appropriateness. While this is not a direct measure of the primary 
outcomes, we will report these as indirect measures of the impact of 
the intervention.

Key Question 2

 Mortality
 Antibiotic resistance
 Medical complications
 Adverse drug effects, including clostridium difficile 
infections

Key Question 3

 Admission to hospital
 Clinic visits (Index, return and subsequent episodes), ED 
visits
 Time to return to work and/or school
 Patient satisfaction
 Quality of life
 Improvement in patient symptoms, speed of improvement
 Use of non-antibiotic treatments, such as over-the-counter 
medications
 Utilization of vaccinations
 Quality metrics

Key Question 4

Intermediate outcomes, such as improved knowledge regarding use of 
antibiotics for acute RTI (clinician and/or patient), or improved 
shared decision making

Key Question 5

Adverse effects of the strategy, such as increased time burden on 
clinicians, sustainability of intervention (e.g. measures of continued 
effectiveness over time), diagnostic resource use associated with POC 
testing, diagnostic coding (e.g. ICD billing codes) according to 
desired action (prescribe/not prescribe)

Timing

    Any duration of follow-up.

Setting

I. Outpatient care settings including institutional settings
II. Emergency care settings
III. Other settings, such as school or workplace

Study Design

    We will prioritize comparative studies with concurrent control 
groups (e.g. randomized controlled trial, prospective and retrospective 
cohort studies including database studies). For areas in which direct 
comparative evidence is lacking, we will include before-after studies, 
with or without a control group and with or without repeated measures.

    Dated: June 16 2014.
Richard Kronick,
AHRQ Director.
[FR Doc. 2014-14962 Filed 6-26-14; 8:45 am]
BILLING CODE 4160-90-M
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