Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

For adults and children who present with uncomplicated influenza, what is the comparative effectiveness of early treatment interventions for reducing complication rates?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

A comparison of antivirals for influenza (primarily neuraminidase inhibitors) to each other or to placebo

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

If treatment can be administered within 36 hours after symptom onset:

1. Persons with lab-confirmed or highly suspected influenza infection at high risk for developing complications.
2. Persons requiring hospitalization for lab-confirmed or highly suspected influenza infection at high risk for developing complications.
3. Outpatients with lab-confirmed or highly suspected influenza infection who are not at increased risk of complications and:

• who wish to shorten duration of illness or
• who are in close contact with persons at high risk of complicated influenza.

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Important subpopulations would include pregnant women, immunocompromised hosts and the elderly.

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

• Reduction in serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases)
• Reduction in duration of hospitalization or hospitalization rates
• Reduction in time to return to work or school
• Reduction in all-cause and influenza-specific mortality rates

Describe any health-related risks, side effects, or harms that you are concerned about.

• Mortality
• Common adverse events associated with treatment (e.g., diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose, and throat infections)
• Less common adverse events (e.g. self-harm, delirium)
• Drug resistance

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Infectious diseases, including HIV/AIDS

AHRQ Priority Populations

• Low income groups
• Minority groups
• Women
• Children
• Elderly
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

• Medicaid
• Medicare
• State Children's Health Insurance Program (SCHIP)

Importance

Describe why this topic is important.

According to the 2009 Guideline by the Infectious Diseases Society of America (IDSA) for seasonal influenza, the majority of persons infected with influenza exhibit self-limited, uncomplicated, acute febrile respiratory symptoms or are asymptomatic. Benefits of influenza antiviral treatment administered within the first 36 hours of symptom onset (i.e., early treatment) have been reported in clinical trials primarily comprised of healthy adults with uncomplicated influenza. However, rates of influenza and secondary complications vary from year to year and across studies, which complicates interpretation of the evidence.

Early influenza treatment is recommended for adults and children with laboratory confirmed or highly suspected influenza virus infection who are at higher risk for complications of influenza infection and severe illness. However, studies of higher risk populations are more limited, particularly among hospitalized patients and children age < one year.

For adults and children with laboratory confirmed or highly suspected influenza virus infection who are not at increased risk of complications, early treatment may be considered to shorten the duration of illness or transmission to others at high risk, or to further reduce their relatively low risk of complications secondary to influenza infection. Yet given the largely self-limiting nature of the illness, an already low risk of secondary complications and the potential for drug resistance and adverse effects of treatment, there is uncertainty in the benefit of influenza treatment in this population and corresponding variability in practice.

According to the stakeholder panel convened for the AHRQ topic identification project, the IDSA has no plans at this time to update their seasonal influenza guideline. In light of the uncertainty in the risks and benefits of early influenza treatment, a systematic review is needed to address the safety and effectiveness of antivirals for a range of

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

This topic was given a high priority by a multi-disciplinary stakeholder panel (including patient and employer perspectives) convened to identify and select important research questions on respiratory tract infections amenable for systematic review.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

The stakeholder panel noted the uncertainty in the benefits of antiviral treatments in adults and children with uncomplicated influenza. There is also uncertainty about the extent of benefit in terms of reducing complications in higher risk patients because of the limited number of studies in those populations, and the fact that studies have not been published.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

A report would inform clinical decision-making for patients, payers and providers.

Describe the timeframe in which an answer to your question is needed.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

This topic nomination is relevant to all populations, including the healthy, but particularly to high risk populations such as children, the elderly, persons with chronic medical conditions (e.g., heart disease, diabetes, obesity), Native American/Alaskan Natives, and persons with compromised immune systems (e.g., HIV/AIDS, cancer treatment).

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

A report would inform clinical decision-making for patients, payers and providers.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program

The Blue Cross and Blue Shield Association Technology Evaluation Center is an Evidence-based Practice Center of AHRQ.