The Connecticut Department of Public Health (CT DPH) became concerned about error rates and inconsistencies between LeadCare package inserts and the Advisory Committee for Childhood Lead Poisoning Prevention’s (ACCLPP) POC recommendations for confirmatory tests. CT DPH consulted with scientists who informed the ACCLPP guidelines, about their concerns. In January 2016, CT DPH notified pediatricians and hospital laboratories via a “circular letter” that venous results from LeadCare instruments were not an acceptable form of confirmation.¹⁶ Circular Letter 2016–02 also briefly described the differentiation of moderate and high complexity testing for confirmation.

As a result of their investigation, CT DPH found certain laboratories used as “reference labs” were, unbeknownst to pediatricians, using the moderate complexity LeadCare Ultra/Plus instruments for confirmatory analysis. Differences exist between the underlying analytic ASV method of the LeadCare II, intended for POC use, and the LeadCare Ultra/Plus instruments being used to confirm screening results.^17,18 These differences include: the number of channels, and therefore tests, for analysis at the same time, the freshness of sample matrix from time of draw, how samples are transferred to sensors, whether carbon particles are part of the analytical process, and the limits of detection. Additionally, CT DPH learned that due to quick turnaround time, providers were basing clinical decisions on whether or not to chelate using results derived from LeadCare instruments which do not meet the ACCLPP-recommended definition of confirmatory test utilizing high complexity analytic methods.⁶

On May 17, 2017, CT DPH learned of the Class I FDA recall through the CDC Health Advisory via the Association of State and Territorial Health Officials (ASTHO) email listserv. Following the recall of the LeadCare venous feature and CDC’s subsequent retesting recommendations, CT DPH sent out a second circular letter that informed providers of the recall and recommendations and required all labs using LeadCare to inform referring pediatricians to determine if patients needed retesting. CT DPH also worked diligently with the Medical Director of the Department of Children and Families (DCF) to determine which children needed retesting. Additionally, CT DPH worked with hospitals to gather paired data on venous samples analyzed using both LeadCare and high complexity methods to further understand potential discrepancies. Analysis revealed differences for BLLs greater than 5 µg/dL (as measured by LeadCare II) ranging from −28 to +4.3 µg/dL between paired results for LeadCare II and high complexity methods (unpublished data). Therefore, differing medical courses of action may have been prescribed depending on which analytical method was used.

Informing healthcare providers and laboratories that venous results obtained using LeadCare instruments were not acceptable prior to the FDA recall likely reduced the number of children who required retesting in CT. To ensure confirmatory testing is appropriately done, health departments may want to consider educating providers and laboratories, particularly hospital labs, regarding the important differences, such as detection limits, between the various laboratory methods. In addition, healthcare providers can denote the blood sample type and whether the sample is for screening or confirmatory purposes to better advise the analyzing lab and health department responsible for collecting and following up on blood lead test results.

The New Jersey Department of Health (NJ DOH) identified 11 providers representing 24 user sites in New Jersey that reported blood lead test results on venous samples that were analyzed on either a LeadCare II or LeadCare Ultra instrument. Providers included: local health departments (LHDs), health care professional offices, hospitals, and independent laboratories. The NJ DOH contacted each user site by phone to instruct the laboratory director to cease analyzing venous samples on LeadCare instruments and to inform them that further guidance would be provided about the FDA recall and CDC health advisory. The NJ DOH faxed a FAQ information sheet, the FDA notification, the retesting protocol, and a sample patient notification letter to each user site. Additionally, the NJ DOH used a Family Health Warm Line to address FAQs from the public regarding the health advisory.

Fifteen thousand children were identified by the NJ DOH as meeting the CDC retesting criteria. Two LHDs were impacted by the warning, resulting in 4,700 children requiring retesting according to the CDC recommendations. The NJ DOH provided a list of identified children to the impacted LHDs.

In reviewing blood lead test results for the impacted providers, the NJ DOH noted an abnormally high quantity of homogenous results for an independent laboratory. Of 956 reports to the NJ DOH between May 2011-June 2016, 944 (98.7%) were reported with a value of 3.0 µg/dL. The LeadCare II instrument has a limit of detection of 3.3 µg/dL; however, the results of 3µg/dL may be the result of rounding and highlight the importance of reporting non-integer test results to at least one digit to the right of the decimal point particularly for results below 10 µg/dL. When the NJ DOH attempted to contact the independent laboratory about the warning and advisory, the phone number was no longer in service. A web search for additional contact information revealed multiple news articles regarding a U.S. Federal Bureau of Investigation (FBI) investigation regarding the provider. The Child and Adolescent Health Program (CAHP) forwarded its concerns regarding the possible falsification of medical records to the NJ DOH’s Office of Legal and Regulatory Compliance. Subsequently, the issue was forwarded to the NJ Deputy Attorney General, Division of Criminal Justice for further investigation. Ultimately, the owners of the independent laboratory pled guilty and forfeited assets in 2016. As of April 2017, the medical fraud case has led to 51 convictions, including 38 doctors, with more than a dozen people awaiting sentencing. News accounts report that it is the largest number of medical professionals ever prosecuted in a federal bribery case, with over $150 million in billed payments from Medicare and private insurance over eight years.¹⁹

The warning and advisory provided an opportunity for the NJ DOH to update its LeadCare user contact list and to reinforce regulatory reporting requirements. Another positive outcome arising from the recall is that NJ DOH’s childhood lead surveillance data management plan has put quality assurance and improvement protocols to identify anomalies in place. An important lesson learned is that intra- and inter-departmental communication can facilitate efficient communication with impacted providers and the public and to address other concerns that affect public health outcomes.

The Oklahoma Childhood Lead Poisoning Prevention Program (OCLPPP) was notified of the FDA advisory officially via email notices through the CDC Health Alert Network. The OCLPPP participated on a CDC conference call on May 18^th describing the potential for falsely low venous test results and clarifying retesting recommendations.

Magellan Diagnostics mails the OCLPPP a monthly, updated list of organizations or providers who have purchased a LeadCare instrument in Oklahoma. The OCLPPP assists new users with reporting, onboarding, and follows up with non-reporters to identify if the instrument is still in use. Because these procedures were already in place, the OCLPPP had contact information for the LeadCare II users affected by the recall and a large hospital laboratory, which was using a LeadCare Ultra instrument. In OCLPPP’s blood lead surveillance and case management system, blood lead test results analyzed using a LeadCare II instrument are identified by the laboratory name “In Office.” The OCLPPP was easily able to identify which patients were impacted by the FDA advisory and CDC’s recommended retesting protocol by analyzing the “In Office” and large hospital data. Relevant data were imported into SAS to identify patients who: (1) were born on or after May 17, 2011; and (2) had a venous specimen tested on a LeadCare instrument; and (3) either had no further blood lead testing or subsequent testing was also a venous specimen on a LeadCare instrument.

The OCLPPP mailed letters to the parents or guardian of the 6,442 children who met the retesting criteria. The letter detailed the advisory and potential for falsely low results in the previous blood lead test, recommended that the child receive a follow-up blood lead test, and provided contact information for the OCLPPP to answer any additional questions or provide assistance. In addition to the “parent” letter, the 383 unique health care providers who ordered the original blood lead tests on the 6,442 children were sent a letter asking them to contact the child’s guardian to schedule a retest. If a parent letter was returned, OCLPPP personnel queried additional databases to see if a newer address was on file and, if so, mailed the letter to the new address. The OCLPPP has not tracked the proportion of children who received the recommended follow-up test because querying the blood lead surveillance system for new blood lead testing data cannot definitively ascertain if the retest was collected due to the recall or as part of standard Oklahoma screening requirements.

CDC guidance was helpful in establishing the criteria for recommended retesting and allowed for standardization of how each state would handle the challenge and uniformity of response from all states. At this time, the OCLPPP is not pursuing additional steps in their response and considers that the matter has been resolved satisfactorily. No changes will be made to the reporting methodology as the current system easily identified LeadCare II test results and could do so again if a similar situation should arise.

In response to the CDC-issued health alert, the Minnesota Department of Health (MDH) issued a health advisory on May 18, 2017 to ensure health care providers and local and tribal health departments were aware of the recall and retesting recommendations. MDH also developed frequently asked questions (FAQ) for health care providers and parents. MDH identified laboratories with LeadCare instruments. Laboratories and local public health agencies were sent lists of patients meeting retesting criteria and were encouraged to ensure patients were retested. Individuals identified as meeting CDC’s retesting criteria through the surveillance system, as well as refugees 6–17 years of age, were recommended for retesting. Retesting was prioritized for persons with previous elevated blood lead levels [EBLLs (defined as ≥ 5 µg/dL)] MDH monitored retesting progress through routine blood lead surveillance and sent updated lists to partners. Logistic regression was used to examine trends in the proportion of individuals retested by the year of their pre-recall blood lead test.

MDH identified fifty-nine laboratories with LeadCare instruments that had analyzed 58,319 samples of venous blood or unknown sample type. Four of those laboratories were using LeadCare Ultra instruments. Of identified test results, 26,491 persons met retesting criteria, including: 18,152 children, 7,113 adults with unknown pregnancy status, and 1,226 refugees; 1,528 had an elevated result from a capillary sample in the 12 months prior to having a venous sample analyzed on a LeadCare instrument (prior EBLL). As of April 30, 2018, MDH had received retests from 4,867 (18.4%) persons, including 3,994 (22.0%) of children, 796 (11.2%) of adult women, and 77 (6.3%) of refugees. Of those with prior EBLLs, 502 (32.9%) received a retest.

The proportion of individuals who received a retest was associated with the year of their pre-recall blood lead test (p<0.01). Only 1.6% (16/1,023) of individuals who had been tested during 2007–2011 received a retest, compared to 10.4% (1,224/11,754) of individuals with a pre-recall test during 2012–2015, and 26.4% (3,627/13,714) of individuals with a pre-recall test during 2016–2017. Of retested persons, 80 (1.6%) had at least one elevated blood lead test result following the recall. Of those, 39 (48.8%) had confirmed EBLLs; 7 (8.8%) had elevated capillary results and have not yet received confirmatory testing; and the remainder were found to be non-cases.

As a group, refugees had the lowest retest rates (6.3%). Because many of these patients were originally tested at their intake examination and did not continue to receive primary care from the same health care provider, it was difficult for the clinics to contact these individuals. Additionally, it was difficult to determine the pregnancy status of adult women, as clinics often do not know whether a patient has become pregnant unless she is receiving regular, ongoing care. Retesting was also minimally successful for individuals tested prior to 2012.

Several factors were instrumental to this response. Purchase records from the manufacturer allowed identification of laboratories that used LeadCare instruments. However, the type of instrument used by each laboratory that submits data to MDH had to be validated because purchase records did not include instruments purchased prior to 2007 or laboratories that are located outside of Minnesota. Quality data in MDH’s surveillance system facilitated generating lists of persons to retest. Voluntary cooperation from laboratories and local public health agencies was invaluable for contacting patients.

MDH was contacted about several instances when a patient attempted to schedule a retesting appointment and experienced difficulty because their clinic schedules appointments using a centralized switchboard, and the operators were unaware of the recall. Several health care providers reportedly told their patients that they did not need to be retested. In addition, some patients received confusing or contradictory messages about who would pay for the retesting appointment. In each of these circumstances, MDH staff attempted to intervene and educate health care providers and clinic staff on the importance of retesting. These difficulties highlight the importance of communicating with all levels of the health care delivery system, including local and tribal health departments, health care providers, staff who schedule appointments for clinics, and health insurance providers and managed care plans. MDH continues to monitor test results received to ensure that laboratories utilizing LeadCare instruments do not test venous samples.