ORIGINAL RESEARCH Public Acceptance of Peramivir During the 2009 H1N1 Influenza Pandemic: Implications for Other Drugs or Vaccines Under Emergency Use Authorizations Sandra Crouse Quinn, PhD; Karen Hilyard, PhD; Nestor Castaneda-Angarita, PhD; Vicki S. Freimuth, PhD
ABSTRACT Objective: The Centers for Disease Control and Prevention estimated that up to 88 million H1N1 influenza cases, 398,000 hospitalizations, and up to 18,050 related deaths, including significant racial and ethnic disparities, occurred between April 2009 and March 13, 2010. The Food and Drug Administration (FDA) approved emergency use authorizations (EUAs), which allowed the distribution of unapproved drugs or the off-label use of approved drugs. In late 2009, peramivir was granted an EUA for patients with severe disease. This study examined factors associated with willingness to take peramivir. Methods: In 2010 we conducted a nationally representative survey with 2079 respondents randomly drawn from the Knowledge Networks research panel. Our completion rate was 56%. Respondents received information about peramivir from a fact sheet and then answered questions about their willingness to take the drug. Results: Overall, 48% of participants indicated that they would probably or definitely take peramivir. Seventy-nine percent definitely would take the drug if their doctor recommended it and there were no alternative treatments. There were significant racial differences in willingness. The term experimental to refer to the drug decreased willingness to accept peramivir among both whites and blacks. Conclusions: Trust in the FDA was important for peramivir acceptance. Particular care must be taken to ensure that patients and their families understand the complex nature of EUA drugs. Lessons learned can inform communication about future EUAs. (Disaster Med Public Health Preparedness. 2015;9:166-174) Key Words: communication, public health, vaccines
T
he Centers for Disease Control and Prevention (CDC) estimated that between 43 million and 88 million H1N1 influenza cases, between 192,000 and 398,000 H1N1-related hospitalizations, and between 8720 and 18,050 H1N1-related deaths occurred between April 2009 and March 13, 2010.1 Across the United States, racial and ethnic minorities were particularly over-represented among those hospitalized and among deaths.2-7 The emergence of a novel influenza virus in the spring of 2009 prompted a race to create an effective vaccine and the need to identify drugs for treatment. With the declaration of a public health emergency by the US Secretary of Health and Human Services in April 2009, the US Food and Drug Administration (FDA) 166
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had the authority to initiate an Emergency Use Authorization (EUA) for unapproved drugs or vaccines.8-12 The EUA mechanism was created to meet exactly the kind of need encountered during this pandemic in which the nation had a new disease threat for which either new drugs or off-label use (use for a purpose other than what the drug was approved for) of approved drugs was necessary. EUAs can also be used for new devices and diagnostic procedures.10 In April 2009, the FDA approved two EUAs for oseltamivir (Tamiflu) and zanamivir (Relenza) as well as EUAs for H1N1 tests and respirators.13 Later in 2009, the FDA approved peramivir IV, which was an unapproved antiviral drug then in adult clinical trials in the United States. It had not been VOL. 9/NO. 2
Copyright © 2015 Society for Disaster Medicine and Public Health, Inc. DOI: 10.1017/dmp.2014.156
Public Acceptance of Peramivir During the 2009 H1N1 Pandemic
tested in any clinical trials with children.14-16 Under the EUA, peramivir IV could be administered intravenously to hospitalized patients under the care of a licensed clinician.14 It had to be accompanied by a CDC fact sheet, which indicated use on adult patients for whom therapy with an intravenous agent was clinically appropriate, that a drug delivery route other than intravenously was not feasible, or that the clinician judged intravenous therapy appropriate owing to other circumstances. The drug was approved for use in pediatric patients if the patient was not responding to either oral or inhaled antiviral therapy or when drug delivery by a route other than the intravenous route was not feasible. There has been little research on public acceptance of EUA drugs and vaccines. The first study to examine EUA acceptance was Quinn et al’s research on public acceptance of the EUA drug oseltamivir for off-label use.9 They found that just over half (54%) of 1469 respondents would definitely or probably accept the drug for themselves and that 49% would definitely or probably accept the drug for their child. That these results hover around the 50% mark suggests that real ambivalence may exist about the acceptance of an EUA drug. Another potential indication of public response toward peramivir comes from the data on an unapproved vaccine under an EUA; fewer than 10% indicated that they would be willing to take such a vaccine, with African Americans least willing, followed by whites, whereas Hispanics were the most willing. Although the literature on EUA drugs and vaccines is limited, the literature on immunization confirms that racial and ethnic minorities are less likely to be immunized for influenza. Those disparities in immunization for influenza persisted through the 2009-2010 H1N1 pandemic, with African American and Hispanic adults vaccinated at lower rates than whites.17 This study examined public willingness to accept peramivir in a hypothetical medical crisis situation and the factors associated with the decision. Given the documented racial and ethnic disparities in H1N1 hospitalizations and immunization status, we were particularly interested in understanding the responses of the 2 largest racial and ethnic minorities, African Americans and Latinos. Although the case presented was hypothetical for the individual, the survey was administered during the 2009 pandemic and thus provided a more realistic opportunity to study EUA acceptance.
METHODS Participants The participants were randomly drawn from the Knowledge Network online research panel, which is representative of the US population. To recruit panel members, the Knowledge Network uses a combination of random-digit dial and addressbased probability sampling methods. The Knowledge Network provides low-income panelists with access to the Internet and
hardware, if necessary, to ensure a representative sample. Panelists participate in online research studies in return for Internet access and hardware or for points redeemable for cash. For this study, the sample was limited to the 3 largest racial/ethnic groups (white non-Hispanics [whites], black non-Hispanics [blacks], and Hispanics) who took the survey from January 22, 2010, to February 1, 2010. There were 2042 participants with a completion rate of 56%. The survey instrument was administered in both English and Spanish. Knowledge Network sends e-mails and telephone reminders to panelists to maximize participation. More information on the Knowledge Network research panel is available from their website (http://www.knowledgenetworks.com).
Measures Demographics Seven demographic variables were measured: gender, age, race, income, education, regular health care provider, and health insurance. Age was categorized into 3 levels. The majority of participants were aged between 35 and 64 years (54.4%). Income was categorized into 4 levels, which showed roughly equal proportions in each level. There were 4 levels of education: below high school, high school, some college, and bachelor’s degree or higher. About 50% of the participants had some college or a bachelor’s degree or higher. Having a regular health care provider and health insurance were measured dichotomously (yes or no).
Susceptibility
Five items measured the participants’ susceptibility to H1N1 flu. The participants’ perception about whether they had influenzalike illness since April 2009 was measured dichotomously (yes or no). Three 4-point Likert items were measured: (1) how likely are you to become ill with swine flu? (2) If you became ill with swine flu, how severe do you think the illness will be? and (3) I am concerned about getting swine flu. Last, whether the participants had a chronic disease (blood disorder, chronic lung disease, diabetes, heart disease, cancer, kidney disorders, liver disorders, and neurological or neuromuscular disorders) was measured.
Trust in Government Action Seven items addressed the level of trust the participant felt in the government handling of the H1N1 pandemic.9 The items measured attitudes toward openness, honesty, commitment, caring, concern, and competence of the government in addressing H1N1; the extent to which the participants believed that the government’s action in response to swine flu was in their personal interest; and how much they believed that the government will protect them from the swine flu. These items were measured on a 4-point Likert scale (a higher number indicated more trust). For the analysis, a composite was created by averaging across all 7 items (Cronbach’s alpha = 0.927). Disaster Medicine and Public Health Preparedness
167
Public Acceptance of Peramivir During the 2009 H1N1 Pandemic
Peramivir Fact Sheet The survey measured perceptions of the peramivir fact sheet. First, participants read this statement from the CDC fact sheet:8 Peramivir is experimental because it is still being studied. It is not approved by FDA for use in the United States. There is limited information known about the safety and effectiveness of using Peramivir to treat people in the hospital with 2009 H1N1 flu. There are no medicines approved by the FDA as safe and effective to treat people in the hospital who have the 2009 H1N1 virus. The information about peramivir was followed by 4 items assessing the information presented: (1) the information about the drug was clearly presented, (2) I understand the information about the drug, (3) I would need more information before I would take the drug, and (4) I believe that the FDA can be trusted to make a good decision about making this drug available for use. These items were measured on a 4-point Likert scale (strongly disagree to strongly agree).
Attitudes Toward Peramivir Four items measured attitudes about peramivir: (1) I am not confident that the drug would be safe for me, (2) words like “experimental” and “still being studied” make me less likely to take the drug even if I was very ill, (3) I would want more information on the drug’s effectiveness, (4) I would want more information about its side effects. These items were measured on a 4-point Likert scale (strongly disagree to strongly agree).
Acceptance of Peramivir Four items measured willingness to take peramivir: (1) if hospitalized, (2) if severely ill, (3) if my doctor recommended it, and (4) if I had no alternative treatments. These items were measured on a 4-point Likert scale (definitely would not to definitely would; strongly disagree to strongly agree), which were dichotomized (yes or no).
Analyses
had less education, and reported less access to health care providers and health insurance than did whites. Furthermore, Hispanics were more susceptible to H1N1 flu than were whites. Blacks and Hispanics had higher trust in government than did whites. We examined predictors by race/ethnicity for willingness to take peramivir under the following conditions: (1) if hospitalized, (2) if severely ill, (3) with a doctor recommendation, and (4) with no alternative (Tables 2 and 3). There were significant differences between racial/ethnic groups in the proportions of participants willing to take peramivir if hospitalized, if severely ill, and if their doctor recommended it. Hispanics were more likely than any other group to take peramivir under these conditions. The difference in the proportions ranged from about 8% to 19%. However, there was no significant difference between groups in the proportion of participants willing to take peramivir if there were no alternatives. Overall, the likelihood of taking peramivir increased across the conditions from “hospitalized” to “severely ill” and from “if doctor recommended” to “no alternative” for all groups. Hispanics also had higher trust in the FDA than did any other group. Whites had higher safety concerns about peramivir than both blacks and Hispanics. There were no other significant differences between groups in their perceptions of the peramivir fact sheet or in their attitudes toward peramivir. For whites, there were 4 significant predictors with large effects for 3 of these 4 situations (hospitalized, severely ill, and doctor recommended). In the context of no alternative, we found a medium effect. Higher-income whites and individuals over 65 were more likely to indicate willingness to take the drugs than were lower income whites or younger adults. White participants who took the seasonal flu vaccine annually were more likely to take peramivir than were those who had never received a seasonal flu vaccine. Last, whites who had influenza-like illness were more willing to take the drug than were those who did not report experiencing influenza-like illness. White participants with a regular health care provider were also more likely to take peramivir.
A logistic regression was performed on each acceptance of peramivir condition predicted by demographic variables, susceptibility, trust in government action, and peramivir fact sheet and attitudes for each racial/ethnic group by using a complex survey design in STATA 12.1. Wald F test statistics and McFadden’s Pseudo R2 are reported for each model. Alpha was set at 0.05. Descriptive statistics and frequencies were performed to examine the distribution of variables.
Whites who trusted the FDA, trusted government action, and reported that the peramivir fact sheet was clearly presented were more willing to take peramivir if their doctor recommended it or if they were severely ill. Whites who felt they needed more information about peramivir were less willing to take the drug under all conditions except when they had no alternative. Whites who were worried about the term experimental in describing peramivir were also less likely to take the drug.
RESULTS
For blacks, there were significant predictors of willingness to take peramivir under the 4 conditions (Tables 2 and 3). There were large effects for all 4 conditions. Blacks with middle income ($50,000-$75,000) were more likely to take
There were significant differences in age, income, education, health care provider, and health insurance between the groups (Table 1). Minorities were younger, had lower income, 168
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TABLE 1 Descriptive Statistics of Variables by Race/Ethnicitya Race/ethnicity
Variable Peramivir if hospitalized, % Peramivir if severely ill, % Peramivir if doctor recommended,% Peramivir if no alternative,% Gender (female),% Age, % 18-34 y 35-64 y ≥65 y Income, %
ABSTRACT Objective: The Centers for Disease Control and Prevention estimated that up to 88 million H1N1 influenza cases, 398,000 hospitalizations, and up to 18,050 related deaths, including significant racial and ethnic disparities, occurred between April 2009 and March 13, 2010. The Food and Drug Administration (FDA) approved emergency use authorizations (EUAs), which allowed the distribution of unapproved drugs or the off-label use of approved drugs. In late 2009, peramivir was granted an EUA for patients with severe disease. This study examined factors associated with willingness to take peramivir. Methods: In 2010 we conducted a nationally representative survey with 2079 respondents randomly drawn from the Knowledge Networks research panel. Our completion rate was 56%. Respondents received information about peramivir from a fact sheet and then answered questions about their willingness to take the drug. Results: Overall, 48% of participants indicated that they would probably or definitely take peramivir. Seventy-nine percent definitely would take the drug if their doctor recommended it and there were no alternative treatments. There were significant racial differences in willingness. The term experimental to refer to the drug decreased willingness to accept peramivir among both whites and blacks. Conclusions: Trust in the FDA was important for peramivir acceptance. Particular care must be taken to ensure that patients and their families understand the complex nature of EUA drugs. Lessons learned can inform communication about future EUAs. (Disaster Med Public Health Preparedness. 2015;9:166-174) Key Words: communication, public health, vaccines
T
he Centers for Disease Control and Prevention (CDC) estimated that between 43 million and 88 million H1N1 influenza cases, between 192,000 and 398,000 H1N1-related hospitalizations, and between 8720 and 18,050 H1N1-related deaths occurred between April 2009 and March 13, 2010.1 Across the United States, racial and ethnic minorities were particularly over-represented among those hospitalized and among deaths.2-7 The emergence of a novel influenza virus in the spring of 2009 prompted a race to create an effective vaccine and the need to identify drugs for treatment. With the declaration of a public health emergency by the US Secretary of Health and Human Services in April 2009, the US Food and Drug Administration (FDA) 166
Disaster Medicine and Public Health Preparedness
had the authority to initiate an Emergency Use Authorization (EUA) for unapproved drugs or vaccines.8-12 The EUA mechanism was created to meet exactly the kind of need encountered during this pandemic in which the nation had a new disease threat for which either new drugs or off-label use (use for a purpose other than what the drug was approved for) of approved drugs was necessary. EUAs can also be used for new devices and diagnostic procedures.10 In April 2009, the FDA approved two EUAs for oseltamivir (Tamiflu) and zanamivir (Relenza) as well as EUAs for H1N1 tests and respirators.13 Later in 2009, the FDA approved peramivir IV, which was an unapproved antiviral drug then in adult clinical trials in the United States. It had not been VOL. 9/NO. 2
Copyright © 2015 Society for Disaster Medicine and Public Health, Inc. DOI: 10.1017/dmp.2014.156
Public Acceptance of Peramivir During the 2009 H1N1 Pandemic
tested in any clinical trials with children.14-16 Under the EUA, peramivir IV could be administered intravenously to hospitalized patients under the care of a licensed clinician.14 It had to be accompanied by a CDC fact sheet, which indicated use on adult patients for whom therapy with an intravenous agent was clinically appropriate, that a drug delivery route other than intravenously was not feasible, or that the clinician judged intravenous therapy appropriate owing to other circumstances. The drug was approved for use in pediatric patients if the patient was not responding to either oral or inhaled antiviral therapy or when drug delivery by a route other than the intravenous route was not feasible. There has been little research on public acceptance of EUA drugs and vaccines. The first study to examine EUA acceptance was Quinn et al’s research on public acceptance of the EUA drug oseltamivir for off-label use.9 They found that just over half (54%) of 1469 respondents would definitely or probably accept the drug for themselves and that 49% would definitely or probably accept the drug for their child. That these results hover around the 50% mark suggests that real ambivalence may exist about the acceptance of an EUA drug. Another potential indication of public response toward peramivir comes from the data on an unapproved vaccine under an EUA; fewer than 10% indicated that they would be willing to take such a vaccine, with African Americans least willing, followed by whites, whereas Hispanics were the most willing. Although the literature on EUA drugs and vaccines is limited, the literature on immunization confirms that racial and ethnic minorities are less likely to be immunized for influenza. Those disparities in immunization for influenza persisted through the 2009-2010 H1N1 pandemic, with African American and Hispanic adults vaccinated at lower rates than whites.17 This study examined public willingness to accept peramivir in a hypothetical medical crisis situation and the factors associated with the decision. Given the documented racial and ethnic disparities in H1N1 hospitalizations and immunization status, we were particularly interested in understanding the responses of the 2 largest racial and ethnic minorities, African Americans and Latinos. Although the case presented was hypothetical for the individual, the survey was administered during the 2009 pandemic and thus provided a more realistic opportunity to study EUA acceptance.
METHODS Participants The participants were randomly drawn from the Knowledge Network online research panel, which is representative of the US population. To recruit panel members, the Knowledge Network uses a combination of random-digit dial and addressbased probability sampling methods. The Knowledge Network provides low-income panelists with access to the Internet and
hardware, if necessary, to ensure a representative sample. Panelists participate in online research studies in return for Internet access and hardware or for points redeemable for cash. For this study, the sample was limited to the 3 largest racial/ethnic groups (white non-Hispanics [whites], black non-Hispanics [blacks], and Hispanics) who took the survey from January 22, 2010, to February 1, 2010. There were 2042 participants with a completion rate of 56%. The survey instrument was administered in both English and Spanish. Knowledge Network sends e-mails and telephone reminders to panelists to maximize participation. More information on the Knowledge Network research panel is available from their website (http://www.knowledgenetworks.com).
Measures Demographics Seven demographic variables were measured: gender, age, race, income, education, regular health care provider, and health insurance. Age was categorized into 3 levels. The majority of participants were aged between 35 and 64 years (54.4%). Income was categorized into 4 levels, which showed roughly equal proportions in each level. There were 4 levels of education: below high school, high school, some college, and bachelor’s degree or higher. About 50% of the participants had some college or a bachelor’s degree or higher. Having a regular health care provider and health insurance were measured dichotomously (yes or no).
Susceptibility
Five items measured the participants’ susceptibility to H1N1 flu. The participants’ perception about whether they had influenzalike illness since April 2009 was measured dichotomously (yes or no). Three 4-point Likert items were measured: (1) how likely are you to become ill with swine flu? (2) If you became ill with swine flu, how severe do you think the illness will be? and (3) I am concerned about getting swine flu. Last, whether the participants had a chronic disease (blood disorder, chronic lung disease, diabetes, heart disease, cancer, kidney disorders, liver disorders, and neurological or neuromuscular disorders) was measured.
Trust in Government Action Seven items addressed the level of trust the participant felt in the government handling of the H1N1 pandemic.9 The items measured attitudes toward openness, honesty, commitment, caring, concern, and competence of the government in addressing H1N1; the extent to which the participants believed that the government’s action in response to swine flu was in their personal interest; and how much they believed that the government will protect them from the swine flu. These items were measured on a 4-point Likert scale (a higher number indicated more trust). For the analysis, a composite was created by averaging across all 7 items (Cronbach’s alpha = 0.927). Disaster Medicine and Public Health Preparedness
167
Public Acceptance of Peramivir During the 2009 H1N1 Pandemic
Peramivir Fact Sheet The survey measured perceptions of the peramivir fact sheet. First, participants read this statement from the CDC fact sheet:8 Peramivir is experimental because it is still being studied. It is not approved by FDA for use in the United States. There is limited information known about the safety and effectiveness of using Peramivir to treat people in the hospital with 2009 H1N1 flu. There are no medicines approved by the FDA as safe and effective to treat people in the hospital who have the 2009 H1N1 virus. The information about peramivir was followed by 4 items assessing the information presented: (1) the information about the drug was clearly presented, (2) I understand the information about the drug, (3) I would need more information before I would take the drug, and (4) I believe that the FDA can be trusted to make a good decision about making this drug available for use. These items were measured on a 4-point Likert scale (strongly disagree to strongly agree).
Attitudes Toward Peramivir Four items measured attitudes about peramivir: (1) I am not confident that the drug would be safe for me, (2) words like “experimental” and “still being studied” make me less likely to take the drug even if I was very ill, (3) I would want more information on the drug’s effectiveness, (4) I would want more information about its side effects. These items were measured on a 4-point Likert scale (strongly disagree to strongly agree).
Acceptance of Peramivir Four items measured willingness to take peramivir: (1) if hospitalized, (2) if severely ill, (3) if my doctor recommended it, and (4) if I had no alternative treatments. These items were measured on a 4-point Likert scale (definitely would not to definitely would; strongly disagree to strongly agree), which were dichotomized (yes or no).
Analyses
had less education, and reported less access to health care providers and health insurance than did whites. Furthermore, Hispanics were more susceptible to H1N1 flu than were whites. Blacks and Hispanics had higher trust in government than did whites. We examined predictors by race/ethnicity for willingness to take peramivir under the following conditions: (1) if hospitalized, (2) if severely ill, (3) with a doctor recommendation, and (4) with no alternative (Tables 2 and 3). There were significant differences between racial/ethnic groups in the proportions of participants willing to take peramivir if hospitalized, if severely ill, and if their doctor recommended it. Hispanics were more likely than any other group to take peramivir under these conditions. The difference in the proportions ranged from about 8% to 19%. However, there was no significant difference between groups in the proportion of participants willing to take peramivir if there were no alternatives. Overall, the likelihood of taking peramivir increased across the conditions from “hospitalized” to “severely ill” and from “if doctor recommended” to “no alternative” for all groups. Hispanics also had higher trust in the FDA than did any other group. Whites had higher safety concerns about peramivir than both blacks and Hispanics. There were no other significant differences between groups in their perceptions of the peramivir fact sheet or in their attitudes toward peramivir. For whites, there were 4 significant predictors with large effects for 3 of these 4 situations (hospitalized, severely ill, and doctor recommended). In the context of no alternative, we found a medium effect. Higher-income whites and individuals over 65 were more likely to indicate willingness to take the drugs than were lower income whites or younger adults. White participants who took the seasonal flu vaccine annually were more likely to take peramivir than were those who had never received a seasonal flu vaccine. Last, whites who had influenza-like illness were more willing to take the drug than were those who did not report experiencing influenza-like illness. White participants with a regular health care provider were also more likely to take peramivir.
A logistic regression was performed on each acceptance of peramivir condition predicted by demographic variables, susceptibility, trust in government action, and peramivir fact sheet and attitudes for each racial/ethnic group by using a complex survey design in STATA 12.1. Wald F test statistics and McFadden’s Pseudo R2 are reported for each model. Alpha was set at 0.05. Descriptive statistics and frequencies were performed to examine the distribution of variables.
Whites who trusted the FDA, trusted government action, and reported that the peramivir fact sheet was clearly presented were more willing to take peramivir if their doctor recommended it or if they were severely ill. Whites who felt they needed more information about peramivir were less willing to take the drug under all conditions except when they had no alternative. Whites who were worried about the term experimental in describing peramivir were also less likely to take the drug.
RESULTS
For blacks, there were significant predictors of willingness to take peramivir under the 4 conditions (Tables 2 and 3). There were large effects for all 4 conditions. Blacks with middle income ($50,000-$75,000) were more likely to take
There were significant differences in age, income, education, health care provider, and health insurance between the groups (Table 1). Minorities were younger, had lower income, 168
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Public Acceptance of Peramivir During the 2009 H1N1 Pandemic
TABLE 1 Descriptive Statistics of Variables by Race/Ethnicitya Race/ethnicity
Variable Peramivir if hospitalized, % Peramivir if severely ill, % Peramivir if doctor recommended,% Peramivir if no alternative,% Gender (female),% Age, % 18-34 y 35-64 y ≥65 y Income, %
