Robert P. Wise

Infections and human tissue transplants: review of FDA MedWatch reports 2001–2004

BackgroundMore than 1.5 million tissue allografts are transplanted annually in the U.S. As part of the federal effort to improve tissue safety, FDA’s May 2005 Current Good Tissue Practices (CGTP) Rule requires tissue establishments to report to FDA serious infectious adverse events following allograft transplantation. To provide baseline data, we summarize reports of such infections received by FDA prior to the CGTP Rule.MethodsWe reviewed reports received by FDA’s MedWatch adverse event reporting system during 2001–2004. Our case definition was a reported infection in a human tissue transplant recipient within 1xa0year of transplantation. We examined demographics, tissue type, clinical outcomes and interventions, infectious organism(s), time from transplant to infection and reporter characteristics.ResultsWe identified 83 reports of infections following allograft transplantations. Median patient age was 40xa0years (range: 1xa0month–87xa0years). The allografts included heart valves (42%), tendons (33%), bones (8%), blood vessels (6%), ocular tissues (5%), and skin (4%). Commonly reported outcomes and interventions were hospitalization (72%), antibiotic therapy (46%) and graft removal (42%). Nine of 11 patients who expired had received heart valves. In 65 reports that identified suspected organisms, bacteria were most common (42), followed by fungi (25) and prions (1). The median time from transplant to infection was 5.5xa0weeks (range: 3xa0days–52xa0weeks). Tissue manufacturers submitted 26% of reports. Among the remaining 74%, the reporters were quality assurance staff, infection control or risk management personnel (45%); physicians (15%); consumers (15%); nurses (13%); and surgical staff (12%).ConclusionThis is the first review of reports to FDA for infections following allograft tissue transplantations. Infections led to serious outcomes and involved many tissue types. Although we were unable to confirm that reported infections were caused by the suspected tissue product, required reporting by tissue establishments and improvements in adverse event investigation will help to improve tissue safety surveillance.

Pediatric deaths reported after vaccination: the utility of information obtained from parents

BACKGROUNDnThe federally administered Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system that receives domestic and foreign reports of adverse events that occur following immunization. This investigation explored whether routinely interviewing parents for follow-up of VAERS pediatric deaths would provide additional information important to vaccine safety.nnnMETHODSnThe study was designed to follow up 100 consecutive pediatric deaths reported to VAERS by interviewing a parent and a healthcare provider (HCP) for each case. Several strategies contributed to successful follow-up. A standardized questionnaire was utilized to interview HCPs and parents. Overall and specific group frequencies (HCPs and parents) were calculated for each variable. McNemars statistical tests of exact inference were calculated to assess whether there were statistically significant differences between HCP and parent knowledge by case for various variables.nnnRESULTSnThe median age of the cases was 4 months. Approximately half of the deaths were attributed to sudden infant death syndrome. In many instances, the information was equivalent in quality. For certain variables, such as knowledge of the childs position when found in distress, more parents than HCPs indicated that they knew the answer.nnnCONCLUSIONSnConducting parental and HCP follow-up for pediatric deaths reported to VAERS was resource intensive. In some instances, parents were more likely than HCPs to provide information regarding some important variables about the nature of the death. None of the additional information obtained from parents, however, provided a signal or confirmation of a causal link between the vaccine and death.

Clarification of FDA and The Joint Commission reporting requirements for US tissue recipient adverse reactions.

In the September issue of Cell and Tissue Banking, Ted Eastlund’s article, ‘‘Bacterial infection transmitted by human tissue allograft transplantation,’’ reviews important issues related to tissue transplantation and transmission of communicable disease. We would like to clarify the Food and Drug Administration (FDA) and The Joint Commission reporting requirements for tissue products and a difference in the types of reports each requires. Effective May 25, 2005, tissue establishments must report to FDA any serious adverse reaction that involves transmission of a communicable disease from a tissue product that they made available for distribution in the United States (US). FDA issued this reporting requirement as part of its Current Good Tissue Practice final rule. Mandatory reports must be submitted to FDA on MedWatch Form FDA 3500A within 15 days of initial receipt of the information. Tissue establishments can refer to FDA guidance, available online, for additional instructions on how to complete a mandatory MedWatch form. FDA also requires these establishments to investigate any tissue recipient adverse reaction that involves transmission of communicable disease. In contrast, organizations accredited by The Joint Commission that store or issue tissue in the US are required to report all tissue recipient adverse reactions. All recipient adverse reactions, including communicable disease transmission or other complications suspected of being directly related to tissue use, are to be investigated and reported directly to the establishment that supplied the tissue product. The Joint Commission implemented its new standards