Please summarize national guidelines and clinical trials and literature surrounding use of oseltamivir (Tamiflu) for use in the critically ill population.

Comment by InpharmD Researcher

Available guidelines recommend initiating standard-dose oseltamivir as soon as possible in all hospitalized patients with suspected or confirmed influenza, including those presenting more than 48 hours after symptom onset. In critically ill patients, observational studies have associated neuraminidase inhibitor treatment with lower mortality, including when treatment is initiated more than 48 hours after symptom onset, although the lack of adequately powered randomized trials limits certainty regarding the magnitude of this benefit. Available randomized evidence does not support increasing oseltamivir to double the standard dose, as higher doses have not demonstrated improved viral clearance or clinical outcomes. Evidence supporting treatment beyond 5 days is primarily observational, although longer treatment may be considered for patients who remain severely ill or have evidence of ongoing viral replication. Overall, standard-dose oseltamivir remains the best-supported antiviral strategy for critically ill patients, with treatment duration individualized according to clinical course and evidence of persistent viral shedding.

Background

A 2026 Centers for Disease Control and Prevention (CDC) clinician summary recommends initiating oral or enterically administered oseltamivir as soon as possible in all hospitalized patients with suspected or confirmed influenza, without awaiting laboratory confirmation; observational evidence indicates that benefit is greatest with early treatment but may persist when treatment is initiated more than 48 hours after symptom onset. No sufficiently powered, randomized, placebo-controlled trials of neuraminidase inhibitor monotherapy have been completed in hospitalized patients; however, observational studies have associated treatment with shorter hospitalization and reduced risks of intensive care unit (ICU) transfer, invasive mechanical ventilation, or death, although some studies have not demonstrated a mortality reduction. Standard-dose oseltamivir achieves therapeutic concentrations in critically ill adults, including limited data involving administration through gastric tubes and use during continuous renal replacement therapy or extracorporeal membrane oxygenation, whereas available evidence does not indicate additional clinical benefit from higher dosing. The optimal treatment duration in severe or complicated influenza remains uncertain; longer treatment may be considered for patients who remain severely ill after 5 days or have prolonged lower respiratory tract viral replication, with decisions guided by clinical judgment and, when appropriate, lower respiratory tract RT-PCR testing. Inhaled zanamivir, intravenous peramivir, and oral baloxavir are not routinely recommended for hospitalized patients because clinical-benefit data are insufficient, and adding baloxavir to a neuraminidase inhibitor did not improve time to clinical improvement in one randomized trial. [1]

The 2024 World Health Organization (WHO) clinical practice guideline conditionally recommends oseltamivir for patients with suspected or confirmed severe influenza, including infections caused by novel influenza A viruses associated with high mortality or an unknown risk of severe disease, based on very-low-quality evidence; treatment should be initiated as early as possible and within 2 days of symptom onset. Evidence was derived from 2 randomized controlled trials involving 104 patients with severe influenza and indicated that oseltamivir may reduce hospitalization duration by 1.63 days versus standard care or placebo (95% confidence interval [CI] 0.45 to 2.81 days fewer; low-certainty evidence), whereas its effects on seasonal influenza mortality (risk ratio [RR] 0.53; 95% CI 0.07 to 4.24) and intensive care unit admission were very uncertain. The recommended adult dosage is 75 mg orally twice daily for 5 days, with renal dose adjustment as indicated; longer treatment may be considered for severe or zoonotic influenza and in immunocompromised patients. Oseltamivir may be administered enterically through an orogastric or nasogastric tube in intubated patients and is well absorbed by this route, but the guideline identifies malabsorption, gastric stasis, ileus, and gastrointestinal bleeding as contraindications to enteric administration. [2]

A 2025 narrative review evaluating antiviral therapy for critically ill patients with influenza reported that no randomized controlled trials have specifically assessed oseltamivir in this population; however, six prospective or retrospective observational studies consistently associated early oseltamivir administration with improved survival or reduced mortality. International guidelines recommend initiating oseltamivir as soon as possible in hospitalized patients with severe influenza, including when illness has been present for more than 48 hours, although the strength and quality of supporting evidence vary. The usual recommended regimen is 75 mg twice daily for 5 days, adjusted for renal impairment; extending treatment to 10 days may be reasonable in immunocompromised patients or those with persistent symptoms and viral shedding at day 5, whereas higher-dose oseltamivir (150 mg twice daily) has not demonstrated faster viral-load reduction or clinical superiority. The review also noted limited and variable pharmacokinetic data in critically ill patients and emphasized that persistent viral replication, particularly among immunocompromised patients, may promote oseltamivir resistance and warrant resistance testing and consideration of an alternative antiviral. [3]

A 2024 network meta-analysis evaluated 8 randomized controlled trials involving 1,424 hospitalized patients with severe suspected or laboratory-confirmed influenza, with 6 trials included in the network meta-analysis. Compared with placebo or standard care, oseltamivir might reduce hospitalization duration (3.37 vs 5.00 days; mean difference [MD] −1.63 days; 95% CI −2.81 to −0.45; low-certainty evidence) but demonstrated little or no difference in time to symptom alleviation (MD 0.34 days; 95% CI −0.86 to 1.54; low-certainty evidence). The effect of oseltamivir on mortality was very uncertain (risk ratio [RR] 0.53; 95% CI 0.07 to 4.24; very-low-certainty evidence), and uncertainty remained regarding ICU admission, progression to mechanical ventilation, and other clinically important outcomes. The included trials did not report treatment timing relative to symptom onset, precluding evaluation of early versus delayed oseltamivir initiation. [4]

A 2014 individual-participant-data meta-analysis of 78 observational studies evaluated neuraminidase inhibitor treatment and mortality among 29,234 patients hospitalized with pandemic influenza A(H1N1)pdm09, including 6,828 patients admitted to critical care; oral oseltamivir accounted for 92% of reported neuraminidase inhibitor use. Among critically ill adults, treatment at any time was associated with lower mortality versus no treatment (adjusted odds ratio [OR] 0.72; 95% CI 0.56 to 0.94), while treatment initiated within 2 days of symptom onset was associated with lower mortality versus later treatment (adjusted OR 0.62; 95% CI 0.49 to 0.77) and no treatment (adjusted OR 0.31; 95% CI 0.20 to 0.47). Treatment initiated more than 2 days after symptom onset was also associated with lower mortality versus no treatment in critically ill adults (adjusted OR 0.65; 95% CI 0.46 to 0.93); corresponding associations were not statistically significant in critically ill children. The authors advocated early neuraminidase inhibitor treatment in adults hospitalized with suspected or confirmed influenza but acknowledged the observational design, inability to adjust specifically for disease severity, potential residual confounding, and missing treatment-exposure data. [5]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Please summarize national guidelines and clinical trials and literature surrounding use of oseltamivir (Tamiflu) for use in the critically ill population.

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Tables 1-4 for your response.

Oseltamivir for Critically Ill Patients with Influenza: A Randomised Trial

Design

Randomized controlled trial

N= 442

Objective

To evaluate the efficacy of oseltamivir in critically ill patients with influenza

Study Groups

Oseltamivir x 5 days (n= 162)

Oseltamivir x 10 days (n= 156)

No antiviral (n= 124)

Inclusion Criteria

Critically ill patients aged ≥ 12 years old with confirmed influenza infection requiring intensive care unit (ICU) admission

Exclusion Criteria

Patients with contraindications to oseltamivir, those who had received more than 48 hours of antiviral therapy prior to enrollment, imminent death expected within 24 hours

Methods

Patients were randomly assigned to receive one of two dosing regimens of oseltamivir or no antiviral. Oseltamivir was dosed at 75 mg administered enterally twice daily for 5 or 10 days. Treatment was continued until discharge or completion of 5 or 10 day treatment course, whichever came first.

Duration

Follow-up period of 90 days

Outcome Measures

Primary: Mortality at 90 days

Secondary: Duration of hospital and ICU stay, duration of mechanical ventilation

Baseline Characteristics

Baseline characteristic	5-day oseltamivir (n=162)	10-day oseltamivir (n=156)	No antiviral (n=124)
Age, years, median (IQR)	60 (49–70)	60 (51–70)	63 (51–71)
Female sex at birth	73 (45.1%)	63 (40.4%)	47 (37.9%)
Body mass index, median (IQR)	27 (24–34); n=129	27 (23–32); n=129	28 (23–31); n=116
APACHE II score, median (IQR)	15 (11–21); n=157	18 (12–25); n=148	16 (11–24); n=121
Influenza A	144/162 (88.9%)	138/156 (88.5%)	111/124 (89.5%)
Influenza B	10/162 (6.2%)	15/156 (9.6%)	8/124 (6.5%)
SARS-CoV-2 coinfection	1/162 (0.6%)	4/156 (2.6%)	3/124 (2.4%)
Symptoms before randomization, days, median (IQR)	5 (3–7); n=143	5 (3–7); n=129	5 (3–8); n=101
Received oseltamivir before randomization	81 (50.0%)	64 (41.0%)	40 (32.2%)
Clinical Frailty Scale, median (IQR)	3 (2–4); n=162	3 (2–4); n=155	3 (2–4); n=122
Invasive mechanical ventilation	77 (47.5%)	83 (53.2%)	48 (38.7%)
PaO₂/FiO₂ ratio, median (IQR)	166 (125–240); n=138	160 (110–228); n=138	178 (135–247); n=112
Vasopressor support	70 (43.2%)	86 (55.1%)	47 (37.9%)
ECMO	0/157 (0%)	2/150 (1.3%)	0/123 (0%)
Cardiovascular SOFA score, median (IQR)	1 (0–3); n=162	3 (0–4); n=155	1 (0–3); n=122
Lactate, mmol/L	1.5 (1.0–2.3); n=149	1.8 (1.2–3.1); n=143	1.5 (1.0–2.3); n=118
Creatinine, μmol/L	88 (71–150); n=157	97 (71–168); n=153	9 (62–150); n=119¹
eGFR, mL/min/1.73 m²	75.8 (41.8–100.2); n=157	71.2 (32.8–97.1); n=153	75.9 (38.4–100.8); n=119

Results

Outcome	5-day oseltamivir (n=162)	10-day oseltamivir (n=156)	No antiviral (n=124)	Comparative result vs no antiviral
Primary: 90-day all-cause mortality	32/162 (19.8%)	30/155 (19.4%)	17/124 (13.7%)	Adjusted OR: 2.13 (95% CrI, 1.03–4.52) and 2.17 (1.05–4.64), respectively
Survival time through day 90	-	-	Reference	Adjusted HR: 1.35 (0.72–2.49) and 1.29 (0.67–2.43), respectively
Organ support-free days through day 28, median (IQR)	22 (0.5–26)	21 (0–25.5)	23 (12.75–27)	Adjusted OR: 1.28 (0.78–2.11) and 1.33 (0.80–2.21)
Disease progression among patients not invasively ventilated at baseline¹	23/85 (27.1%)	13/73 (17.8%)	15/76 (19.7%)	Adjusted OR: 2.53 (0.92–7.26) and 1.65 (0.52–4.98)
ICU-free days	Not reported descriptively	Not reported descriptively	Reference	Adjusted HR: 1.20 (0.88–1.65) and 1.18 (0.85–1.64)
Hospital-free days	Not reported descriptively	Not reported descriptively	Reference	Adjusted HR: 1.12 (0.82–1.53) and 1.07 (0.78–1.48)

Adverse Events

Common Adverse Events: Nausea (15% vs. 10%); vomiting (8% vs. 5%)

Serious Adverse Events: No significant difference between groups

Study Author Conclusions

Oseltamivir did not significantly reduce mortality at 90 days in critically ill patients with influenza, but it was associated with a reduction in the duration of ICU stay and mechanical ventilation.

Critique

The study was well-designed with a robust randomization process, but the lack of significant mortality benefit may limit its impact. The study's strengths include a large sample size and comprehensive data collection. However, the exclusion of patients who had received prior antiviral therapy may limit the generalizability of the findings to all critically ill influenza patients.

Table 1 References:
[6] REMAP-CAP Investigators. Oseltamivir for critically ill patients with influenza: a randomised trial. SSRN. Preprint published online July 27, 2026. doi:10.2139/ssrn.7172531

Combining baloxavir marboxil with standard-of-care neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trial
Design	Randomised, parallel-group, double-blind, placebo-controlled, superiority trial N= 366
Objective	To test whether combining the cap-dependent endonuclease inhibitor baloxavir marboxil with standard-of-care neuraminidase inhibitors would result in improved clinical outcomes compared with neuraminidase inhibitor monotherapy in hospitalised patients with severe influenza
Study Groups	Baloxavir group (n= 241) Control group (n= 125)
Inclusion Criteria	Patients aged 12 years or older who were hospitalised with laboratory-confirmed influenza and had a National Early Warning Score 2 (NEWS2) of 4 or greater
Exclusion Criteria	Patients weighing less than 40 kg, expected to be discharged or die within 48 h, or who had received antiviral treatment for 48 h or longer before screening
Methods	Patients were randomly assigned to receive either baloxavir plus neuraminidase inhibitors (NAIs) or placebo plus NAIs. Baloxavir was administered orally on day 1 and day 4 (40 mg for bodyweight <80 kg, or 80 mg for ≥80 kg), and on day 7 if no clinical improvement had occurred by day 5. NAIs included oseltamivir, zanamivir, and peramivir, administered according to local standard practice. The primary endpoint was time to clinical improvement, defined as time to a NEWS2 of 2 or lower for 24 h or hospital discharge, whichever came first
Duration	January 8, 2019, to March 16, 2020
Outcome Measures	Primary: Time to clinical improvement S Secondary: Safety analyses
Baseline Characteristics		Baloxavir group (n= 208)*	Control group (n= 114)*
	Age, years	59.4 ± 19.6	61.9 ± 19.9
	Female	99 (48%)	53 (46%)
	Asian	39 (19%)	21 (18%)
	White	151 (73%)	86 (75%)
	Current influenza episode	197 (95%)	107 (94%)
	Requires ventilation or supplemental oxygen	143 (69%)	80 (70%)
	NEWS2 at baseline	6.72 ± 2.25	6.69 ± 2.33
	Antiviral treatment ≤48 h before screening** Oseltamivir/oseltamivir Peramivir Laninamivir octanoate	64/76 (84%)* 11/76 (14%)* 1/76 (1%)*	39/46 (85%)* 7/46 (15%)* 0/46*
	The modified intention-to-treat infected (mITTI) population (ie, all patients who were randomly assigned to treatment, received a dose of study drug, and were RT-PCR-positive for influenza at any timepoint according to the treatment assigned at randomisation) *As a proportion of patients who received antiviral treatment within 48 h before screening. Prior antiviral use within 48 hours before screening was similar between groups, occurring in 37% of patients in the baloxavir group and 40% in the control group, with oseltamivir being the most commonly used antiviral. Among patients receiving baloxavir, 78% received two doses, 16% received three doses, and 6% received one dose. Baseline demographic and clinical characteristics were generally similar between treatment groups.
Results		Baloxavir group (n= 208)	Control group (n= 114)	p-value
	Median time to clinical improvement, hours (95% CI)	97.5 (75.9-117.2)	100.2 (75.9-144.4)	0.467
	Median time to cessation of viral shedding, hours (95% CI)	23.9 (23.2-24.5)	63.7 (46.4-68.1)	<0.0001
	Among 322 patients in the modified intent-to-treat infected population (mITTI), 208 received baloxavir and 114 received control, with 87% having influenza A. Median time to clinical improvement was similar between groups (97.5 vs 100.2 hours, median difference −2.7 hours, 95% CI −53.4 to 25.9, P=0.467). Baloxavir plus a NAI was well tolerated, with serious adverse events occurring in 12% vs 15% of patients, respectively. Mortality was 2% with baloxavir compared with 6% with control, with no deaths considered treatment-related.
Adverse Events	Baloxavir plus NAI was well tolerated, with no new safety signals observed. Serious adverse events occurred in 12% of patients in the baloxavir group versus 15% in the control group. One serious adverse event (orthostatic hypotension) was considered related to treatment in the control group.
Study Author Conclusions	Combining baloxavir with NAIs did not result in superior clinical outcomes compared with NAIs alone. The combination was well tolerated, suggesting that combination antivirals would not be routinely indicated in clinical practice for hospitalised patients with severe influenza
Critique	The study was well-designed as a double-blind, placebo-controlled trial, providing robust data on the efficacy and safety of combining baloxavir with NAIs. However, the lack of significant clinical improvement with combination therapy suggests limited benefit over standard NAI treatment. The study's limitations include the inability to assess the effect of baloxavir monotherapy and the potential impact of late treatment initiation. Additionally, the study did not evaluate the efficacy of the combination against influenza B due to the limited number of such cases in the cohort.

Table 2 References:
[7] Kumar D, Ison MG, Mira JP, et al. Combining baloxavir marboxil with standard-of-care neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trial. Lancet Infect Dis. 2022;22(5):718-730. doi:10.1016/S1473-3099(21)00469-2

Effectiveness of prolonged versus standard‐course of oseltamivir in critically ill patients with severe influenza infection: A multicentre cohort study
Design	Retrospective cohort study of prospectively collected data N= 2397
Objective	To investigate the effectiveness of prolonged versus standard‐course oseltamivir treatment among critically ill patients with severe influenza
Study Groups	Prolonged oseltamivir (n= 1943) Standard oseltamivir (n= 454)
Inclusion Criteria	Adults with severe acute respiratory infection and acute respiratory failure requiring ICU admission, microbiological confirmation of influenza A or B virus infection by rt-PCR, and received oseltamivir at ICU admission for at least 5 days
Exclusion Criteria	Children younger than 15 years old, subjects with missing data on antiviral therapy or ICU survival, and patients with ICU length of stay less than 5 days
Methods	Retrospective analysis of a database including adults with influenza infection admitted to 184 ICUs in Spain from 2009 to 2018. Prolonged oseltamivir was defined as treatment beyond 5 days, standard as 5 days. Propensity score matching was used to control for confounding factors. Primary outcome was all-cause ICU mortality, analyzed through Cox regression and RCSs.
Duration	2009 to 2018
Outcome Measures	Primary: All-cause ICU mortality Secondary: Differences in ICU length of stay and duration of invasive mechanical ventilation
Baseline Characteristics		Total (N = 2397)	Prolonged Oseltamivir (n= 1943)	Standard Oseltamivir (n = 454)	p Value
	Age (years)	56 (44–67)	54 (43–66)	61 (50–72)	<0.001
	Male	1458 (60.8%)	1176 (60.5%)	282 (62.5%)	0.57
	APACHE II score	16 (12–22)	16 (12–21)	18 (14–24)	<0.001
	SOFA score	6 (4–8)	6 (4–8)	6 (4–9)	0.51
	Pulmonary infiltrates in chest X-ray >2	1240 (51.7%)	1033 (53.2%)	207 (45.6%)	0.004
	Type of influenza virus A(H1N1)	1691 (70.5%)	1458 (75%)	233 (51.3%)	<0.001
	Obesity	779 (32.5%)	647 (33.3%)	132 (29.1%)	0.09
	Chronic obstructive pulmonary disease	555 (23.2%)	422 (21.7%)	133 (29.3)	<0.001
	Immunosuppression	370 (15.4%)	291 (15%)	79 (17.4%)	0.22
	Pneumonia	2108 (87.9%)	1742 (89.7%)	366 (80.6%)	<0.001
Results		Prolonged Oseltamivir (n= 1943)	Standard Oseltamivir (n= 454)	p-value
	ICU mortality	387 (22.1%)	119 (28.3%)	0.009
	ICU length of stay, days (IQR)	14 (8–25)	8 (6–14)	<0.001
	Duration of mechanical ventilation, days (IQR)	14 (9–23)	9 (5–16)	<0.001
Adverse Events	Not specifically reported
Study Author Conclusions	Prolonged oseltamivir was associated with reduced ICU mortality in critically ill patients with severe influenza. Clinicians should consider extending the oseltamivir treatment duration to 10 days, particularly in higher-risk groups of prolonged viral shedding.
Critique	The study's strengths include a large sample size and the use of propensity score matching to control for confounding factors. However, limitations include its retrospective design, lack of monitoring for viral shedding duration, and potential for selection bias. The study was conducted in Spain, which may limit generalizability to other regions. Additionally, the cost implications of prolonged treatment were not fully explored.

Table 3 References:
[8] Moreno G, Carbonell R, Daz E, et al. Effectiveness of prolonged versus standard-course of oseltamivir in critically ill patients with severe influenza infection: A multicentre cohort study. J Med Virol. 2023;95(8):e29010. doi:10.1002/jmv.29010

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial
Design	Double blind randomised trial N= 326
Objective	To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza
Study Groups	Double dose oseltamivir (n= 165) Standard dose oseltamivir (n= 161)
Inclusion Criteria	Patients aged ≥1 year admitted to hospital with confirmed severe influenza
Exclusion Criteria	Pregnancy or positive for chorionic gonadotrophin (hCG) in urine, women who were actively breast feeding, a delay of more than 72 hours before treatment with oseltamivir, and severe renal impairment defined by creatinine clearance <10 mL/min
Methods	Patients were randomised to receive double dose (150 mg twice a day or paediatric equivalent) or standard dose (75 mg twice a day or paediatric equivalent) oseltamivir. Treatment was supervised by the research team and continued for five days, with an additional five days for those meeting clinical failure criteria
Duration	April 2007 to February 2010
Outcome Measures	Primary: Proportion of patients with no detectable viral RNA by RT-PCR on day five Secondary: Mortality, mechanical ventilation, admission to intensive care, symptoms, resumption of activity
Baseline Characteristics	At enrollment, the study included 246 children and 80 adults randomized to double-dose or standard-dose oseltamivir. Baseline characteristics were generally similar between treatment groups within both age populations. Children had a mean age of 2.8 years and had been ill for approximately 5 days, while adults had mean ages of 37.9 years in the double-dose group and 45.9 years in the standard-dose group and approximately 5 days of illness. Cough was nearly universal in both populations, while dyspnea, tachypnea, and fever were also common. Adults had a greater burden of severe illness and comorbidities, including lower Karnofsky scores, hypertension, and alcoholism, and were more likely to have received antivirals before enrollment (63–67% vs 10% of children). Radiographic infiltrates were common in both children and adults (77–79% and 90–95%, respectively), while acute respiratory distress syndrome (ARDS) was more frequent in adults (19.5–25.6% vs 2.4–3.3% in children). Adults also more frequently required intensive care, supplemental oxygen, and mechanical ventilation. Viral subtypes varied across groups, with H3N2 predominating in children and H1N1-pdm09 and H3N2 commonly identified in adults.
Results	The primary virological endpoint showed no significant difference between double- and standard-dose oseltamivir. On day 5, viral RNA was undetectable in 72.3% of patients receiving double-dose compared with 68.2% receiving standard-dose oseltamivir (difference 4.2%, 95% CI −5.9% to 14.2%, p=0.42), with similar findings in children and adults and across influenza subgroups. Viral shedding continued to decline after day 5, with no meaningful differences between treatment groups through day 14. Day 5 clinical failure also did not differ significantly between groups (9.9% vs 13%, p=0.44). Overall mortality was 6.4%, with similar rates between double- and standard-dose groups (7.3% vs 5.6%, p=0.54), and most deaths occurred in patients with H5N1 influenza. Requirements for supplemental oxygen, intensive care, and mechanical ventilation, as well as their durations, were similar between groups. No H275Y resistance mutations were detected in H1N1-pdm09 or H5N1 infections. Among patients with seasonal H1N1, the H275Y mutation was present at baseline in 56% of sequenced samples, and some patients developed the mutation during treatment, predominantly in the standard-dose group, although no clear differences in viral clearance or clinical outcomes were observed.
Adverse Events	Oseltamivir was generally well tolerated; 55 (16.9%) patients had 75 treatment emergent adverse events with similar rates between the two arms. The most common adverse events were respiratory failure, diarrhoea, and multi-organ failure. Overall 14 (19%) adverse events were judged as possibly, probably, or definitely related to oseltamivir.
Study Author Conclusions	There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital.
Critique	The study was well-designed as a double-blind randomised controlled trial, providing robust evidence. However, the study was not powered for subgroup analyses, and the heterogeneous population characteristics may limit the generalizability of the findings. Additionally, the study was not placebo-controlled, which could have provided more definitive conclusions on the efficacy of oseltamivir in severe influenza

Table 4 References:
[9] South East Asia Infectious Disease Clinical Research Network. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. BMJ. 2013;346:f3039. Published 2013 May 30. doi:10.1136/bmj.f3039