NIC 2005 Jeanne M. Santoli, MD, MPH National Immunization Program Overview of the 2004-05 Influenza Season — Disease, Vaccine Supply, Vaccine Uptake NIC 2005 Jeanne M. Santoli, MD, MPH National Immunization Program This morning, I will talk with you about the 2004-05 influenza season. I will give a brief status of the disease activity, vaccine supply, and vaccine uptake and then provide an overview of how we arrived at this point. The information I am going to share with you involves the work of a great number of individuals and I am privileged to speak with you on their behalf.

Disease First, I will provide a brief update about disease activity.

Influenza Activity Update This graph depicts the number and % of specimens testing positive for influenza viruses reported by WHO and National Respiratory and Enteric Virus Surveillance System collaborating laboratories in the US by week, through March 12 (week 10). As you can see, disease activity was low in the US from October-mid December and steadily increased during January and early February. The peak occurred during February and disease activity continues to decline. As of March 12, only 18 pediatric deaths have been reported (vs. 153 in 2003-04) but reports of deaths associated with lab-confirmed influenza are expected to increase before the end of season.

Vaccine Supply As for vaccine supply this year . . .

We learned of a severe and unanticipated shortfall of vaccine on Oct 5 with the announcement that Chiron would not be able to supply the US market this season. This slide contains a headline from one of the many news stories that appeared in early October highlighting the dramatic reduction in supply.

Vaccine uptake Despite the severity of the supply disruption, however, the news about vaccine uptake this season is extremely positive. Beginning on November 1, 2004, questions were added to the Behavioral Risk Factors Surveillance System (BRFSS) survey to collect information about influenza vaccine use for all persons aged >= 6 months of age, including receipt of vaccine, priority group status, and reasons for non-vaccination. The BRFSS is a monthly telephone survey conducted by state health departments which includes about 5,000 households per week and collects information about one sampled adult and one sampled child (if there is one) per household. The next two slides present information about persons interviewed between January 1-22, 2005, the final vaccine coverage data collected by BRFSS for the 2004-05 influenza season.

Adult Influenza Vaccination Coverage September – December 2004 BRFSS, 2005* (n = 19,091) Population n 2004-05 % 2003 NHIS** % Aged 18-64y, high-risk§ 2,669 28.0 34.2 Aged ≥65y 4,747 58.9 65.5 Health-care workers with patient contact 1,204 42.6 40.1 Priority adults¶‡ 8,454 43.1 47.8 Nonpriority adults 10,637 8.3 19.6 This slides shows coverage among adults in each of the priority groups as well as non-priority adults. The column in red indicates vaccine coverage reported by BRFSS participants and the column in yellow provides comparison data collected by the National Health Interview Survey in 2003. The comparison isn’t a perfect one because of differences in the way that BRFSS and NHIS collect data, but it does give some context in which to view the coverage levels achieved this season. The first thing I’d like to point out in the red column is the contrast between coverage among adults in priority groups this year (43.1%) compared with non-priority adults (8.3%). This difference indicates that efforts to target vaccine as outlined in the October 5, 2004 interim recommendations were effective. A second key finding is the relatively high coverage among each of the priority groups, which is fairly close to coverage from 2003-04. In looking at the coverage among non-priority adults, we see that it decreased from 19.6% last year to 8.3% this year, which represents more than 16 million adults who stepped aside this year in order to make vaccine available for persons in priority groups. *Interviews conducted January 2-22, 2005 †Confidence interval §Asthma; other lung, heart, or kidney problems; diabetes, weakened immune system, anemia, or pregnancy ¶Persons can be included in more than one priority group. ‡Includes persons in households with children aged <6m. ** Data from the 2003 National Health Interview Survey reflect vaccinations received in the 2002-03 and 2003-04 influenza seasons.

Child Influenza Vaccination Coverage September – December 2004 BRFSS, 2005* (n = 4,424) Population n 2004-05 % 2002-03 ** % Aged 6-23m 403 57.3 7.7 Aged 2-17y, high-risk§ 478 43.8 ------ Priority children 881 50.7 Nonpriority children¶ 3,543 12.4 This slide presents vaccination coverage among children and also shows evidence of effective implementation of the interim recommendations with 50.7% of priority children vaccinated versus 12.4% of non-priority children. Another very notable finding is the coverage among 6-23 month old children, which was 57.3%, quite an accomplishment given the fact that this was the first year of a full recommendation for this age group and in light of the supply shortage. Final BRFSS data, through the end of February, have also been collected. Some of you may have seen a preview of those data at yesterday’s BRFSS workshop and the data will be published in the MMWR on April 1. *Interviews conducted Jan 2-22 †Confidence interval §Asthma; other lung, heart, or kidney problems; diabetes, weakened immune system, anemia, or aspirin therapy. ¶Includes persons in households with, and out-of-home care givers of, children aged <6m, and others with rare high-risk conditions. **Data from the 2003 National Immunization Survey.

The Problem With the announcement that Chiron would not be able to supply the US market US licensed vaccine supply decreased by ~50% More than 50% of the remaining supply of inactivated vaccine already distributed to approximately 34,000 customers Distribution primarily by sanofi pasteur (formerly Aventis Pasteur), using partial shipments So, in early October, we found ourselves with about half of the vaccine supply we anticipated, and with more than half of the remaining supply already distributed to approximately 34,000 customers. Distribution had been carried out primarily by sanofi pasteur (formerly Aventis Pasteur), using partial shipments.

Doses of sanofi pasteur TIV Distributed Before 10/5/04 This chart depicts the provider types to which the first 33 million doses had been distributed prior to October 5, 2004. As you can see, approximately 50% of doses had been distributed to primary care providers and hospitals.

Immediate Actions Taken ACIP provided interim recommendations on October 5 identifying priority groups Number of persons recommended for vaccination drops from 188 million to 98 million Sanofi pasteur voluntarily ceased shipment of vaccine, begins discussions with CDC FDA authorized redistribution of influenza vaccine State/local public health officials redistributed vaccine, identified sites for vaccination of high risk persons, reduced inappropriate use of vaccine, sub prioritized vaccine use as needed Several immediate actions were taken: The ACIP provided interim recommendations on Oct 5 and identified priority groups for vaccination. This decreased the number of persons recommended for vaccination from 188 million to 98 million. Sanofi pasteur voluntarily ceased shipment of vaccine and began discussions with CDC about how to proceed. The FDA authorized the redistribution of vaccine among providers. And state/local ph officials took on many tasks, including redistribution of vaccine, identifying sites for vaccination of high risk individuals, and reducing inappropriate use of vaccine.

Efforts to Augment Supply Sanofi pasteur freed up additional doses by reaching out to large customers with outstanding orders and produced 2.6 million additional late season doses MedImmune increased production from 1 million doses to 3 million doses DHHS contacted several foreign manufacturers of influenza vaccine to inquire about obtaining vaccine to supplement US vaccine supply under an Investigational New Drug (IND) protocol In addition, efforts were made to augment the supply of available vaccine by sanofi pasteur and MedImmune, who both produced additional doses and the Dept of HHS who contacted a number of foreign manufacturers of influenza vaccine to inquire about purchase of additional vaccine that could be administered via an Investigational New Drug (IND) protocol.

Tracking the Location of Vaccine Detailed proprietary information about vaccine shipments Sanofi pasteur provided vaccine shipment information Vaccine distributors provided pre-booked orders and vaccine shipment information Information on CDC’s Secure Data Network (SDN), accessible to state health officials or designees SDN also used by states to place vaccine orders for their jurisdictions Another key step taken was the development of software to track the distribution of influenza vaccine. Detailed proprietary information was provided by sanofi pasteur and vaccine distributors and this information was made accessible to state health officials or their designees via CDC’s secure data network. This network was also used by states to place vaccine orders for providers in their jurisdictions.

Vaccine Distribution: An Iterative Process Objective: To distribute a scarce resource to the providers most likely to be able to reach priority patients. 1. Immediately identifiable orders 2. Apportioned vaccine doses 3. Late season strategies As everyone in this this room is well aware, vaccine distribution was an iterative process this year, evolving as information about supply and demand became available. First immediately identifiable orders were addressed; Then states used apportioned doses to allocate to providers in their jurisdictions; And finally, late season strategies were put into place to enhance continued use of vaccine.

Inactivated Vaccine Supply Status October 5, 2004 ~25 million doses ~33 million doses This pie chart depicts the status of inactivated vaccine on October 5, 2004: 33 million doses distributed and approximately 25 million doses, including late season doses, remained to be distributed.

Identifiable Orders Allowed vaccine distribution to resume quickly Included many public health orders placed with Chiron Orders selected for full or partial filling included: State/local public health departments Long term care facilities/hospitals VA/IHS/DoD Providers who care for children (VFC orders, p-free orders, office-based pediatricians) Community immunization providers/VNAA Office-based primary care providers Approximately 13 million doses distributed during October-early December There was an initial focus on immediately identifiable orders in order to resume vaccine distribution as quickly as possible. These orders included many (but not all) public health orders placed with Chiron as well as orders placed with sanofi pasteur by providers serving substantial numbers of high risk patients. Orders selected for full or partial filling included: State/local public health departments Long term care facilities/hospitals VA/IHS/DoD Providers who care for children (VFC orders, p-free orders, office-based pediatricians) Community immunization providers/VNAA Office-based primary care providers Filling of these orders resulted in approximately 13 million doses of vaccine distributed over a 6-8 week period.

Inactivated Vaccine Supply Status Early November 2004 ~12 million doses ~46 million doses At the close of this stage of vaccine distribution, 46 million doses of inactivated vaccine had been (or were in the process of being ) distributed and approximately 12 million doses remained.

State/Local Public Health Officials Pivotal role Relationships with providers, facilities (including licensing) Emergency powers Vaccine redistribution activities Knowledgeable about local supply/demand situation Best suited to identify and address gaps in vaccine distribution During the first weeks of the response, as we were anticipating the next stage of vaccine distribution, it became clear that state/local public health officials should play a central role. First, these individuals play a pivotal role in terms of their existing relationships with providers and facilities, their emergency powers, and their knowledge of the vaccine redistribution activities that had already taken place. Because of their knowledge and expertise about local supply and demand for vaccine, these public health officials were best suited to identify and address gaps in vaccine distribution and ensure community protection.

Apportioned Vaccine Doses ~3.5 million doses filled remaining identifiable public health orders ~8.5 million doses apportioned across states according to unmet need formula Formula developed collaboratively by state and local health officials and CDC Based upon a state’s “share” of unmet national need Unmet need = # of priority persons- total doses delivered Two re-apportionments to redirect vaccine States allocated vaccine across providers from November 9, 2004 to mid January 2005 Thus began the second stage, which involved dividing up the remaining 12 million doses across the states. First, approximately 3-4 million doses were used to fill remaining identifiable public health orders. Then we worked with state and local health officials to develop a formula to apportion the remaining ~8 million doses across the states according to each state’s percentage of the national unmet need. States could then allocate doses from their apportionment to providers and facilities who would purchase the vaccine through a participating distributor. The state ordering process began on November 9 and continued through mid January. The formula used was equitable, but it was imperfect and it became apparent that some states had more vaccine than they needed to reach the priority groups while other states had too little. In response, two reapportionments were conducted to move vaccine (virtually) from states with excess to states with an undersupply.

Broadened Recommendations: December 2004 ACIP reviewed data about vaccine supply and coverage Recommendations broadened to include those aged 50-64 and household contacts at discretion of state/local public health Effective date: January 3, 2005 VFC resolution broadened to include household contacts Effective date: Immediately Midway through this second stage of vaccine distribution, recommendations for use of influenza vaccine were broadened to include two additional groups based on state/local assessment of vaccine supply and demand. The VFC resolution was modified to address this change in the recommendations.

Inactivated Vaccine Supply Status Mid January 2005 ~3.5 million doses ~54.5 million doses By mid-January, this stage of vaccine distribution had largely ended. At that time, approximately 3.5 million doses of inactivated vaccine remained unordered.

Late Season Strategies: Announced 1/27/2005 CDC encourages states to Continue to target high risk individuals Broaden administration of vaccine to make most effective use of existing supply Stockpile strategy Sanofi pasteur distributes doses with a return policy to minimize financial risk to providers VFC transfer strategy Limited amounts of VFC vaccine transferred to state health departments in jurisdictions in which the need for VFC vaccine among eligible children has been met Because the demand for vaccine had decreased considerably (including demand from providers and the public), and in light of increasing disease activity, less than typical vaccine coverage, and remaining vaccine, options for enhancing continued use of vaccine were considered. On Janaury 27, CDC announced three strategies, each aimed at increasing demand for vaccine late in the season and making vaccine more accessible. The first strategy involved encouraging states to broaden vaccine administration to make the most effective use of vaccine. The second strategy involved allowing sanofi pasteur to distribute doses from the CDC influenza stockpile, which represented the vast majority of remaining doses. Sanofi pasteur marketed those doses to private and public providers with a return policy in order to minimize the financial risk to providers, which was becoming an increasingly important barrier to the distribution and ordering system in place during Nov-January. The third strategy involved VFC vaccine purchased for use this season that currently existed in the states. In states where the demand for influenza vaccine among VFC eligible children had been met, we undertook steps to transfer limited amounts of this vaccine out of the VFC program and into the hands of state health departments for non-VFC use.

Doses Distributed in millions (%) Vaccine Production and Distribution: How Does 2004 Compare with Prior Seasons? Year Doses Produced in millions Doses Distributed in millions (%) 1999 77.2 76.8 (99%) 2000 77.9 70.4 (90%) 2001 87.7 77.7 (89%) 2002 95.0 83.0 (87%) 2003 86.9 83.1 (96%) 2004 61.0 56.5 (93%) This table illustrates the total amount of influenza vaccine produced and distributed since 1999. The numbers in parentheses indicate the percent of vaccine remaining undistributed at the end of the season. For 2004-05, approximately 7% of the total licensed vaccine produced remained undistributed, which is about average over the past six years. But given the efforts undertaken target limited supplies of vaccine this year and the number of persons who stepped aside, having vaccine left over at the end of the season gives us pause. Data provided by vaccine manufacturers No data are available on how many doses of influenza vaccine are administered each year.

Conclusions When it comes to influenza, disease, supply, and demand for vaccination are highly unpredictable This influenza season represented a difficult situation with a number of important positive outcomes Relatively high vaccine coverage among priority groups Evidence of successful targeting of vaccine Forging and strengthening of alliances that will serve us well in the face of future public health challenges Alignment of roles during a crisis with routine responsibilities and authorities maximized accomplishments Timeliness of decision-making and implementation is critical—an opportunity for continued improvement This year’s experience underscores the importance of planning for future seasons Start early Anticipate multiple scenarios Involve key stakeholders This season contains a number of lessons for us. It underscores the unpredictability of influenza disease, vaccine supply, and public demand for vaccination. We ended up with a number of positive outcomes despite a drastic reduction in anticipated vaccine supply. These positive outcomes in include the vaccine coverage levels achieved, the effective targeting that took place, and the enhanced partnership between and among public and private sector stakeholders. The most salient accomplishments occurred when there was an alignment between roles during the crisis and routine responsibilities/authorities. The involvement of state/local public health in vaccine allocation is a clear example of this. A key area for improvement at the federal level involves the enhancing the speed at which policy decisions are made. And there is a need for planning, planning, planning. Planning needs to start early, involve key stakeholders, and anticipate multiple scenarios.

A Word of Thanks Any successes that can be claimed rest upon the shoulders of more individuals and groups than can be named Individuals who stepped aside to save vaccine for persons in priority groups Private providers State/local public health officials Sanofi pasteur MedImmune Vaccine distributors FDA and other federal agencies And finally, I’d like to take a moment to recognize some of the individuals and groups whose efforts and dedication contributed to what has been accomplished this season—the credit rests on a good many shoulder, more than I can adequately cover here: First, the persons who stepped aside this season and did not allow concerns about scarcity of vaccine to deter them from looking out for those at increased risk of complications from influenza. Second, the private provider community, who took on the difficult task of asking their patients to step aside and who supported and worked closely with state and local public health officials. Third, the public health officials whose input shaped the vaccinate distribution process this season and who bravely took on the task of distribution within their jurisdictions and dealt with the frustrations of providers and the public that such a start-up system inevitably inspired. Fourth, sanofi pasteur, who took a public health approach to this vaccine supply crisis, and without whose collaboration very little could have been accomplished. Fifth, MedImmune, who increased their production in response to the crisis and worked to target their vaccine toward the ACIP’s priority groups for whom it was indicated. Sixth, the vaccine distributors who participated in our start-up ordering and distribution system, despite its challenges. The role of this group has been less in the spotlight than some others, but it is no less important. Finally, the FDA who authorized vaccine redistribution and scoured the globe for additional vaccine manufacturers, as well as other federal agencies and departments who assessed and reassessed their needs for vaccine throughout the season to make the most of a limited supply.