Clinical Laboratory Improvement Act Research Articles

A-003 Beckman Coulter DxI 9000 Immunoassay Analyzer’s High Sensitivity Troponin I achieves >90% six sigma performance when assessed against clia 2024 performance goals

Abstract Background In July 2024, the Clinical Laboratory Improvement Act (CLIA) proficiency testing (PT) criteria will directly regulate Troponin I performance for the very first time. The new CLIA goal is 0.9 ng/mL or 30%, whichever is greater. CAP previously set a goal of 30% or 3 times the group standard deviation (SD), whichever is greater, a more permissive setting. Estimates of current instrument group performance from an international proficiency testing (PT) survey have shown none of the 5 major diagnostic instruments can achieve the biological minimum goal at a 6-Sigma level, while 4 of the 5 instruments perform at 3 Sigma or below. Performance of these platforms was assessed using the methodology introduced in 2006 by Westgard JO and Westgard SA. The DxI 9000 high sensitivity Troponin I assay was assessed to determine if it could achieve the new CLIA 2024 goals. Methods The DxI 9000 high sensitivity Troponin I assay was assessed with three reagent lots, on both serum and Lithium Heparin (LiHep) samples, following Clinical Laboratory Standards Institute (CLSI) protocols EP05 and EP09 to estimate imprecision and bias. The new CLIA 2024 PT criteria supplied the allowable total error for the standard Sigma-metric calculation: Sigma-metric = (TEa - |bias|) / SD The Sigma-metric predicts not only future problems with PT, but also potential optimization of QC procedures, including fewer Westgard Rules, control levels, even reduced QC frequency which can lead to less cost, time, and materials. Results The majority (91.7%) of data points across the analytical measuring range for DxI 9000’s high sensitivity Troponin I assay from both serum and LiHep samples achieved 6-Sigma performance. For serum, only 8.3% of samples achieved 5-sigma performance. For LiHep, only 4.2% of the performance was 4 Sigma. None of the performance was 3 Sigma or lower. Conclusions The superior precision observed on DxI 9000 high sensitivity Troponin I delivers overwhelming 6-sigma performance when assessed by CLIA’s 2024 goal. This assay is highly unlikely to face PT difficulties and can be optimized for reduced Westgard Rules, reduced control levels leading to a reduction in time, materials, and cost.

B-113 Beckman Coulter DxI 9000 immunoassay analyzer assay performance meets new CLIA 2024 performance goals with highest proportion of Six Sigma performance amongst all major manufacturers

Abstract Background The Clinical Laboratory Improvement Act (CLIA) proficiency testing (PT) criteria will be updated in July 2024 with some goals tightening by up to 40%. It is assumed, but not known, that all assays and instruments will be able to achieve these goals. Using these new CLIA 2024 goals, estimates of current instrument group performance from an international proficiency testing (PT) survey have shown significant differences in quality, calling into question which assays can achieve the new CLIA goals. Currently, the highest performing diagnostic instrument achieves only 35.2% 6-Sigma, while the majority of instruments have less than 15% 6-Sigma performance indicating a higher probability of future PT failures. Methods Eighteen assays that will be governed by new CLIA 2024 goals were assessed for Sigma metric performance on the DxI 9000 immunoassay analyzer: Alpha Fetoprotein (AFP), Beta hCG, Carcinoembryonic antigen (CEA), Cortisol, Creatine Kinase MB (CK-MB), Estradiol, Ferritin, Folate, Follicle-Stimulating Hormone (FSH), Prolactin, Para-thyroid hormone (PTH), Total Prostate specific antigen (Total PSA), Testosterone, Thyroid Stimulating Hormone (TSH), Total Triiodothyronine (TT3),high sensitivity Troponin I, Total Thyroxine (TT4) and Vitamin B12. Precision and bias were determined following CLSI EP5 and EP9 guidelines, measured across 3 reagent lots. CLIA 2024 PT criteria provides the allowable total error for the standard Sigma-metric calculation: Sigma-metric = (TEa - |bias|) / SD Performance of the other major analyzers was assessed using the methodology introduced in 2006 by Westgard JO and Westgard SA. The Sigma-metric predicts future problems with PT and potential optimization of QC procedure opportunities, including fewer Westgard Rules, control levels, even reduced QC frequency and materials leading to less cost and time saved. Results Half (50%) of the assays on DxI 9000 achieves 6-Sigma, outperforming all other major manufacturers in the market who range from only 5% to 35% 6-Sigma. Further, over 78% of the DxI 9000 performance was 4Sigma and higher. Less than 8% of performance fell below 3-Sigma, which was observed at the extreme ends of the reportable range. Conclusions The DxI 9000 assay performance is well designed to meet CLIA 2024’s new PT criteria and has the highest prevalence of 6-sigma assay performance observed on market when compared to the top 5 major instrument manufacturers. Assays with Sigma metrics at 4-Sigma and higher are unlikely to face analytical PT difficulties and can be optimized for reduced Westgard Rules, control levels, and potentially even QC frequency.

Abstract 5023: Analytical validation of the Oncomine™ Dx Express Test using liquid biopsy samples as an IUO assay in a CAP/CLIA lab

Abstract Introduction: The Oncomine™ Dx Express Test (ODxET) is a next-generation sequencing (NGS) test. It can be used as an investigational use only (IUO**) test to detect somatic DNA and RNA alterations in human cell-free total nucleic acid (cfTNA) isolated from plasma samples. This study outlines the analytical validation of the ODxET for relevant single nucleotide variants (SNV) and insertion/deletions (INDEL) in liquid biopsy specimens. The Ion Torrent Genexus™ platform has a short turnaround time with minimal operator input. This study was performed in a College of American Pathologists (CAP™) accredited and Clinical Laboratory Improvement Act (CLIA) licensed laboratory. Methods: Forty-seven unique samples (39 clinical, 3 derived, 2 reference and 3 commercially available DNA controls) were analyzed. All experiments began with sample extraction, except the lower input limit of detection (LLOD). We evaluated limit of detection, variant calling accuracy, and precision. Two control NIST™ samples were sequenced with 3 technical replicates each for INDEL and SNVs analytical accuracy. The LOD was evaluated at both the target input of 2ng/µl (40ng), and the minimum input,0.33ng/µl (6.6ng) with allele frequency (AF) levels at 1%, 0.5%, and 0.25%. The 39 clinical plasma samples were used for variant calling accuracy. Inter-assay reproducibility was assessed by sequencing DNA controls across four runs by different operators over multiple days/systems. Intra-assay repeatability was assessed by sequencing 4 samples in replicate on the same run by one operator on the same day/system. Results: The analytical accuracy and NPV was 100% for SNV/INDEL variants. The 40ng input LOD sensitivity was 96% for SNVs at 0.5% AF and 100% for INDELs at 0.25% Minimum AF. The lower input LOD sensitivity was 89% for SNVs and 100% for INDEL at 1% AF. Variant calling accuracy on samples with pre-characterized data was 100% for the 13 positive samples. Specificity was >99% for all samples including both healthy donor and positive samples. Repeatability was 100% for INDELs and >96% for SNVs, reproducibility was 100% for both variant classes. Conclusion: This validation study to estimate analytical accuracy, limit of detection, variant calling accuracy and precision has demonstrated that the ODxET assay is highly robust in detecting SNV and INDEL mutations in plasma samples and is suitable for use in a CAP/CLIA laboratory as an IUO assay.**=In Vitro Diagnostic use only. Not available in all regions including North America. Citation Format: Juan C. Espinoza, Rajendra Ramsamooj, Akemi Yuki, John Williamson, Diarra Hassell, Madhu Jasti, Suzanne Salazar, David Ginzinger. Analytical validation of the Oncomine™ Dx Express Test using liquid biopsy samples as an IUO assay in a CAP/CLIA lab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5023.

Deceptively simple: Can urine samples from NexScreen cup be re-used for confirmatory testing?

Abstract Background The NexScreen urine drug screen cup (SKU: HCDOAV-8145EF1KT, NexScreen LLC, CO, USA) is a Clinical Laboratory Improvement Act (CLIA)-waived test used at our affiliated mental health institute. Specimens testing positive are sent for Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) confirmation. The manufacturer instructs patients to urinate directly into the NexScreen cup. Doing so raised concern about whether this urine can be re-used for confirmatory testing. Modifying the test by collecting urine in another container before pouring it into the NexScreen cup would reclassify the test as high complexity. This would require further regulatory oversight and negate the convenience of a CLIA-waived test. Requesting the patient to urinate into a second container is not always feasible, as patients may be unable or unwilling to provide another sample. A straightforward solution would be to take specimens from the NexScreen container and use them for confirmatory testing. However, the assay components of the NexScreen drug test strips may contaminate specimens and generate false positives with highly sensitive LC-MS/MS assays. In addition, false negatives on confirmatory testing could occur if NexScreen test strips or the plastic cup adsorb drug compounds from patient urine. The manufacturer provides no guidance in this regard. Objective The goal of this study was to investigate if re-using urine from NexScreen cups for LC-MS/MS confirmatory testing was appropriate. Methods and Results We pooled 25 NexScreen-negative patient specimens and confirmed by LC-MS/MS that no NexScreen-detectable compounds were present in this pool. To evaluate drug conjugate leaching into the specimens, 30 mL blank urine was poured into 10 NexScreen cups, followed by incubation for 1 hour at room temperature, which is the maximum time recommended by the manufacturer for reading NexScreen results. All 10 cups tested negative for all drugs. In addition, none of the negative samples tested positive on LC-MS/MS for any drug compounds targeted, proving that the test strips in the NexScreen cups do not interfere with LC-MS/MS testing. Next, to assess drug adsorption by the NexScreen drug cup, a representative analyte from each of the 13 drug classes was chosen and spiked at concentrations slightly above the published NexScreen positivity cutoffs. Then, 30 mL of spiked urine was placed into 10 NexScreen cups, incubated for 1 hour, and aliquots were sent for LC-MS/MS confirmation. Interestingly, 11 of the 13 analytes achieved at least 95% recovery, while buprenorphine and THC-COOH had 94% and 87% recoveries, respectively, indicating some minor adsorption. However, all analytes, including buprenorphine and THC-COOH, recovered well above the cutoffs for LC-MS/MS assays, suggesting that there is no significant adsorption to alter confirmatory results. Conclusion Use of an aliquot from a NexScreen cup for confirmatory testing is appropriate within the manufacturer-recommended readability window of 1-hour post-collection.

POLICING FORENSIC EVIDENCE

POLICING FORENSIC EVIDENCE

Analytical Performance Validation of Next-Generation Sequencing Based Clinical Microbiology Assays Using a K-mer Analysis Workflow.

Next-generation sequencing (NGS) enables clinical microbiology assays such as molecular typing of bacterial isolates which is now routinely applied for infection control and epidemiology. Additionally, feasibility for NGS-based identification of antimicrobial resistance (AMR) markers as well as genetic prediction of antibiotic susceptibility testing results has been demonstrated. Various bioinformatics approaches enabling NGS-based clinical microbiology assays exist, but standardized, computationally efficient and scalable sample-to-results workflows including validated quality control parameters are still lacking. Bioinformatics analysis workflows based on k-mers have been shown to allow for fast and efficient analysis of large genomics data sets as obtained from microbial sequencing applications. We here demonstrate applicability of k-mer based clinical microbiology assays for whole-genome sequencing (WGS) including variant calling, taxonomic identification, bacterial typing as well as AMR marker detection. The wet-lab and dry-lab workflows were developed and validated in line with Clinical Laboratory Improvement Act (CLIA) guidelines for laboratory-developed tests (LDTs) on multi-drug resistant ESKAPE pathogens. The developed k-mer based workflow demonstrated ≥99.39% repeatability, ≥99.09% reproducibility and ≥99.76% accuracy for variant calling and applied assays as determined by intra-day and inter-day triplicate measurements. The limit of detection (LOD) across assays was found to be at 20× sequencing depth and 15× for AMR marker detection. Thorough benchmarking of the k-mer based workflow revealed analytical performance criteria are comparable to state-of-the-art alignment based workflows across clinical microbiology assays. Diagnostic sensitivity and specificity for multilocus sequence typing (MLST) and phylogenetic analysis were 100% for both approaches. For AMR marker detection, sensitivity and specificity were 95.29 and 99.78% for the k-mer based workflow as compared to 95.17 and 99.77% for the alignment-based approach. Summarizing, results illustrate that k-mer based analysis workflows enable a broad range of clinical microbiology assays, potentially not only for WGS-based typing and AMR gene detection but also genetic prediction of antibiotic susceptibility testing results.

Individualized Quality Control Plan (IQCP): Is It Value-Added for Clinical Microbiology?

The Center for Medicaid and Medicare Services (CMS) recently published their Individualized Quality Control Plan (IQCP [https://www.cms.gov/regulations-and-guidance/legislation/CLIA/Individualized_Quality_Control_Plan_IQCP.html]), which will be the only option for quality control (QC) starting in January 2016 if laboratories choose not to perform Clinical Laboratory Improvement Act (CLIA) [U.S. Statutes at Large 81(1967):533] default QC. Laboratories will no longer be able to use "equivalent QC" (EQC) or the Clinical and Laboratory Standards Institute (CLSI) standards alone for quality control of their microbiology systems. The implementation of IQCP in clinical microbiology laboratories will most certainly be an added burden, the benefits of which are currently unknown.

S02.3 Extra-Genital CT/GC Testing by NAATS: Use in Screening and Prevalence of Infection in MSM, Issues in Validation

Most Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections in men who have sex with men (MSM) are not in the urethra. This has been confirmed often since it was...

Hospital Laboratory Leadership and the Dyad Model of Management

The medical director of the hospital-based clinical laboratory is ultimately responsible, according to Clinical Laboratory Improvement Act (CLIA) regulations, for the quality of services provided. The medical director, however, may have little authority over laboratory operations, possibly because of the organizational structure of the laboratory or the limited interaction between the medical director and hospital administrators. The Dyad (pair) model of management is ideal for implementation in the clinical laboratory. In this model, as applied in the hospital laboratory setting, the medical director and a member of the hospital administration team form a dyad to embrace shared accountability and to implement a common vision and shared goals. As a result, the hospital administrators view the laboratory through the perspective of the medical director, and the medical director gains a defined mechanism to exert influence over the laboratory production process. * COO : chief operating officer; CLIA : Clinical Laboratory Improvement Act; TAT : turnaround time; CAP : College of American Pathologists; VP : vice president; CEO : chief executive officer; QC : quality control; PT : proficiency testing; CE : continuing education

Laboratory Self-Inspection: Using a Checklist for Safety and Health Audits

Objective: To help readers gain an understanding of the laboratory professional’s role in the safety and health self-inspection process, the contents of the Occupational Safety and Health Administration (OSHA)’s Laboratory Safety Guidance document, the purpose of selfinspection, and essential design elements that should be included in a safety checklist. The Occupational Safety and Health Act of 1970 gives laboratory workers the legal right to a safe workplace. Quality assessment (QA) is a requirement for clinical laboratories under the Clinical Laboratory Improvement Act (CLIA) for evaluating all facets of the laboratory’s technical and nontechnical operations. Most clinical laboratory accreditation programs include safety as part of QA and promote the use of checklists. An effective self-inspection program engages laboratory staff to participate in the QA process with an easy-to-use, concise checklist. This list is used to verify whether safety equipment, standards, and practices required by the Occupational Safety and Health Administration (OSHA), other applicable regulatory agencies, and institutional policies are available and observed to be in use in the workplace. I present herein a report about a laboratory self-inspection program for a university-based biomedical research laboratory; this program can easily be adapted for use in a clinical laboratory.

Implementation of External Quality Assessment Scheme in Clinical Chemistry for District Laboratories in Bhutan.

External Quality Assessment Scheme (EQAS) involves evaluation of a number of laboratories by an outside agency on the performance of a number of laboratories based on their analytical performance of tests on samples supplied by the external agency. In developing countries, establishment of national EQAS by preparing homemade quality control material is a useful scheme in terms of resources and time to monitor the laboratory performance. The objective of this study is to implement an EQAS to monitor the analytical performance of the district laboratories in Bhutan. Baseline information was collected through questionnaires. Lyophilized human serum including normal and abnormal levels were prepared and distributed to 19 participating laboratories. Nine routine analytes were included for the study. Their results were evaluated using Variance index scores (VIS) and Coefficient of variations (CV) was compared with Clinical Laboratory Improvement Act (CLIA) Proficiency Testing Criteria (PT) for each analyte. There was significant decrease in CV at the end of the study. The percentages of results in acceptable VIS as 'A' were 63, 60, 66, 69, 73 and 74, 75, 76 and 79% in November 2009-July 2010 respectively. From our results, we concluded that, establishment of EQAS through distribution of home-made quality control material could be the useful scheme to monitor the laboratory performance in clinical chemistry in Bhutan.

IRB perspectives on the return of individual results from genomic research

PurposeReturn of individual research results from genomic studies is a hotly debated ethical issue in genomic research. However, the perspective of key stakeholders—institutional review board (IRB) professionals—has been missing from this dialogue. This study explores the positions and experiences of IRB members and staff regarding this issue. MethodsIn-depth interviews with 31 IRB professionals at six sites across the United States. ResultsIRB professionals agreed that research results should be returned to research participants when results are medically actionable but only if the participants want to know the results. Many respondents expected researchers to address the issue of return of results (ROR) in the IRB application and informed-consent document. Many respondents were not comfortable with their expertise in genomics research and only a few described actual experiences in addressing ROR. Although participants agreed that guidelines would be helpful, most were reticent to develop them in isolation. Even where IRB guidance exists (e.g., Clinical Laboratory Improvement Act (CLIA) lab certification required for return), in practice, the guidance has been overruled to allow ROR (e.g., no CLIA lab performs the assay). ConclusionAn IRB–researcher partnership is needed to help inform responsible and feasible institutional approaches to returning research results.Genet Med 2012:14(2):215–222

Comments on the participation in proficiency programs and promotion of quality in transfusion services of Minas Gerais

Comments on the participation in proficiency programs and promotion of quality in transfusion services of Minas Gerais

Testing Men Who Have Sex With Men for Urethral Infection With Chlamydia trachomatis and Neisseria gonorrhoeae Is Only Half the Job, and We Need the Right Tools

Standard operating procedure in STD clinics commonly has been to test urethral specimens when evaluating males, whether they are heterosexual or men who have sex with men (MSM). Rectal or oropharyngeal specimens may be tested in MSM with symptoms, or in some clinics as screening tests if individuals report sexual practices that would indicate risk of infection at these sites. In a report in this issue of Sexually Transmitted Diseases, Marcus and colleagues studied the prevalence of infection with Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in the urethra, the oropharynx, and rectum in asymptomatic MSM visiting the San Francisco STD clinic.1 A retrospective analysis of 3398 patient visits found CT or GC at 549 (16.2%) of those visits. The prevalence of infections among these asymptomatic men ranged from a high of 7.8% for rectal CT to a low of 0.4% for urethral GC. Strikingly, 83.8% of CT and GC infections would have been missed if only urethral screening was performed. What was found in the Marcus study, and in others, as well, is that the majority of infections with CT/GC in MSM are not in the urethra. The first major study to make this point was performed by Kent and colleagues, in 2 clinics in San Francisco, where they found that 50% of chlamydial and gonococcal infections were extraurethral.2 That finding has been confirmed by a number of approaches, including retrospective chart reviews and prospectively designed studies (Table 1). While these studies have focused on rectal and pharyngeal CT/GC infections in MSM, it must be noted that such infections are far from rare in women.12,13 In many clinical settings, the infections in women will be seen more often than those in men. These extragenital infections should not be ignored now, and we need more research to better define their potential consequences. Both CT and GC are recognized as causes of proctitis, and even asymptomatic infections have been associated with HIV transmission. 14 Current CDC recommendations call for routine screening of the oropharynx and rectum in MSM who may be exposed to GC or CT at those sites. It is not clear whether pharyngeal infections have a major direct impact on health. But evidence is emerging that infection can be transmitted from the oropharynx to the urethra of sex partners, thus continuing chains of infection.15 All of the cited studies have been made possible by the introduction and application of highly sensitive and specific nucleic acid amplification tests (NAATs) for the diagnosis of CT and GC infections. NAATs are recommended for routine diagnosis of CT/GC infections.15 Where direct comparisons have been done, it has been shown that the increment in sensitivity for NAATs as compared to culture is greater with pharyngeal and rectal specimens than it is with cervical and urethral specimens. An approximate doubling of the number of infections detected has been obtained with NAATs. 4,11 Alas, there remains a gap wherein the best tests are not readily available to the patients and providers who need them. Several NAATs are commercially available and have received FDA clearance for male and female urine specimens, urethral swabs from men, and cervical and vaginal swabs from women. Unfortunately, none have been cleared by the FDA for pharyngeal or rectal specimens. But the CDC, recognizing the superior performance of these tests used on these specimens, has taken an unusual step and recommended the use of NAATs for diagnosis of CT/GC in oropharyngeal and rectal specimens, even though such use has not received FDA clearance. 16 The

Quality Management Issues in the Assisted Reproduction Laboratory

In the United States, the Clinical Laboratory Improvement Act (CLIA) of 1988 describes requirements and guidelines for implementing a quality control/quality assurance (QC/QA) program for moderate and high complexity laboratories. These requirements and guidelines apply to Assisted Reproductive Technology (ART) laboratories as well. The general topic of QC and QA as it pertains to in vitro fertilization (IVF) and embryo transfer (ET) is extensively reviewed. This review summarizes many of the QC and QA events that contribute to the advancement of knowledge in this biotechnological field. These events include control of the culture environment inside and outside of the incubator, as well as factors that affect culture media. This review also discusses, in considerable detail, the QC and the QA that pertain to equipment used within the laboratory and how to control for potential contaminants, which reside within the laboratory. This review provides evidence to indicate the need for laboratory personnel to monitor quality improvement issues on a continuous basis. Personnel must be willing to change as improvements in technology occur in order to meet the ever-evolving demands of a more difficult patient population. Suggestions for meeting these demands are offered.

Research Highlights

Research Highlights

Human tumor cell lysates as a protein source for the detection of cancer antigen-specific humoral immunity

Measurement of humoral tumor-specific immunity can predict what proteins are specific tumor antigens, be used to evaluate patient diagnosis or prognosis, and function as a method by which one can measure the effects of an immune intervention, such as a vaccine. Antibody assays can easily be adapted to high throughput formats; however, specific reagents needed for assay development often are not available. Developing methods to produce large quantities of purified recombinant tumor antigen proteins for indirect ELISA is both laborious and expensive. In addition, using proteins derived from E. coli might preclude the detection of certain antibody epitopes. We questioned whether a human tumor cell-based ELISA could be developed to assess antibody immunity to common tumor-associated antigens and whether such an ELISA could be optimized to the clinical standards needed for evaluation of large scale trials. Assays were based on the detection of HER-2/neu and p53 antibodies by capture ELISA, using human tumor cell lysate as a protein source. After optimization, the HER-2/neu and p53 ELISA intra-assay coefficients of variation (CV) of positive control sera were consistently 9% and 12%, respectively, at a 1:100 dilution. The HER-2/neu and p53 inter-assay CV of positive control sera over a 5-month time period were 20% and 15%, respectively. The sensitivity and specificity of the ELISAs were evaluated based on comparison to immunoblot. Analysis demonstrated the HER-2/neu ELISA had a specificity of 77% and sensitivity of 89%, and the p53 ELISA had a specificity of 100% and sensitivity of 93%. Cell-based ELISA can be developed to be Clinical Laboratory Improvement Act (CLIA)-compliant and the flexibility of the approach will allow adaptation of the assay to multiple tumor antigen systems.

A Quality Assurance Program for AIDS Clinical Trials Group Pharmacology studies

The goal of the AIDS Clinical Trials Group (ACTG) Pharmacology Quality Assurance (QA) Program is to provide mechanisms that assure, in a timely manner, the validity and integrity of the data produced in pharmacology-related ACTG research protocols. In 2000, a new QA Program for ACTG Pharmacology Studies was strategized and implemented. By identifying the common problems and errors occurring within prior clinical studies and utilizing the quality procedures inherent within Good Clinical Practice (GCP) Regulations, Good Laboratory Practice (GLP) Regulations and the Clinical Laboratory Improvement Act (CLIA), specific program components were designed. The latter regulation, CLIA, is required for ACTG Pharmacology Support Laboratories (PSL) generating laboratory results directly impacting patient care. New pharmacology QA practices were implemented throughout the conduct of ACTG clinical trials. This document provides an overview of the present ACTG Pharmacology QA program. Copyright © 2005 John Wiley & Sons, Ltd.

Oversight of Genetic Testing: An Update

Oversight of Genetic Testing: An Update

The College of American Pathology Inspection Process

The College of American Pathology Inspection Process