Docket Management
Docket: 02N-0466 - Randomized Dose Response Study of Dryvax in Children Ages 2 to 5
Comment Number: EC -455

Accepted - Volume 4

Comment Record
Commentor Dr. james oleske Date/Time 2002-12-02 12:25:55
Organization umdnj/njms
Category Health Professional

Comments for FDA General
Questions
1. General Comments Dr. Leslie K. Ball, OHRP After careful review of the documents, including the well reasoned responses of experts, I would be reluctent to recommend implementation with Dryvax immunization in children 1-5 yrs. as proposed in investigators' protocol. While put forth that this more than minimal risk study in healthy children could be justified under HHS 45 CFR 46.407 and FDA 21 CFR 50.54, I would argue that there are several factors not adequatly adressed. The real and present danger of smallpox used as an agent in bioterrorism has not been clearly stated by the investigators nor the NIAID, especially for children in 1-5 yr. age group. How much greater than 0 is the risk? How many covert stockpiles are suspected? There are a number of practical problems in the use of Dryvax. After a 25 yr hiatus, I have recently administered this vaccine to 13 labratory workers at the Center for Labratory Investigation (CLI), NJMS under the CDC 002 protocol. The vaccine is contained in small top-heavy vials that are easily spilled. The technique of administration using bifocated needles by multiple puncture is awkward at best and requires skills that most health professionals no longer have. While the 40 children in the proposed study can be expected to have this vaccine administered appropriately, the translation of this study for large numbers of children will be associated with mishaps that will increase errors and potential serious adverse effects. While historically five punctures have been used in children, present adult studies utilized 15 punctures and the investigators should consider the need to introduce the virus effectively by increasing the numbers of punctures in children. In addition, by convention individuals had received smallpox on the left deltoid area of the upper arm. If this protocol is to be undertaken the investigators should explicitely follow this practice. The stated expectations that safer more easily administered vaccinea vaccines may be available as early as 2003 argues that using 20 year old+ lots of vaccinea (Dryvax) would not be prudent. For the present time, Dryvax should be used for emergency response and healthcare personnel. Based on the evidence presented, it appears that Dryvax can be diluted at least 1-5 while retaining potency. It is also reassurring that significant adverse events bave not been common in recipients of Dryvax but it would be unwise to conclude that when large numbers of individuals are vaccinated, there would not be serious adverse effects and death. While there is logic and convenience in choosing 2-5 age range, this is also a more vulnerable population with less likelihood of exposure to smallpox if used as a bioterrorist weapon. If the protocol were to proceed, I would prefer that 1-5 dilution of Dryvax be utilized with topical coverage as outlined in the protocol. It is laudable that the investigators propose long term follow up however, most children should be offered this follow up, rather than the small group proposed in this study. The informed consent is a long, complex document that needs to be further developed to assure understanding by parents and more accurately reflect the risks entailed for these young children.




EC -455