Laboratory-Developed Tests: A Legislative and Regulatory Review.

BACKGROUND: Twenty-five years ago, the Food and Drug Administration (FDA) asserted in a draft document that "home brew" tests-now commonly referred to as laboratory-developed tests (LDTs)-are subject to the same regulatory oversight as other in vitro diagnostics (IVDs)4. In 2010, the FDA began work on developing a proposed framework for future LDT oversight. Released in 2014, the draft guidance sparked an intense debate over potential LDT regulation. While the proposed guidance has not been implemented, many questions regarding LDT oversight remain unresolved. CONTENT: This review provides an overview of federal statutes and regulations related to IVDs and clinical laboratory operations, with a focus on those potentially applicable to LDTs and proposed regulatory efforts. Sources reviewed include the Code of Federal Regulations, the Federal Register, congressional hearings, guidance and policy documents, position statements, published literature, and websites. SUMMARY: Federal statutes regarding IVDs were passed without substantive evidence of congressional consideration toward the concept of LDTs. The FDA has clear oversight authority over IVD reagents introduced into interstate commerce. A 16-year delay in publicly asserting FDA authority over LDTs, the pursuit of a draft guidance approach toward oversight, and establishment of regulations under the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) applicable to LDTs contributed to community uncertainty toward LDT oversight. Future regulatory and/or legislative efforts may be required to resolve this uncertainty.

Laboratory Workup of Lymphoma in Adults: Guideline From the American Society for Clinical Pathology and the College of American Pathologists.

CONTEXT.­: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. OBJECTIVE.­: To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. DESIGN.­: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.­: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS.­: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

Laboratory Workup of Lymphoma in Adults.

OBJECTIVES: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. THE AIM OF THIS REVIEW IS TO: develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. METHODS: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of the literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were derived based on the available evidence, the strength of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. RESULTS: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions about specimen suitability, diagnostic capabilities, and correct utilization of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

Reliability and Validity of Proposed Risk Stratification Methods for Laboratory Developed Tests.

OBJECTIVES: To determine whether different laboratory developed test (LDT) risk stratification proposals would assign differing levels of risk to selected LDTs as a measure of the validity of those proposals, and whether there would be differing interrater agreement rates as a measure of the reliability of those proposals. METHODS: A total of 4 reviewers applied 6 proposals for risk stratification of 4 LDTs. Interrater agreement was calculated as a measure of the reliability of the proposals. Also, a consensus risk categorization and concordance rate for each LDT was developed as a measure of the validity of the proposals. RESULTS: Interrater agreement rates (reliability) ranged from 38% to 100%, and concordance rates (validity) ranged from 20% to 100%. CONCLUSIONS: A spectrum of reliability and validity was observed depending on the policy used and the LDT categorized. Before implementation or legislation of risk-stratification methods, large evaluations of reliability and validity should be conducted on any proposed method.

Training in laboratory management and the MBA/MD in laboratory medicine.

The business of medicine requires more than just the knowledge and skills necessary to provide quality patient care. A growing number of opportunities are available for physicians to learn how to better manage the business side of their practices. Today's clinical laboratories, particularly those in health care organizations under pressure to efficiently use limited resources, benefit from having management and leadership specifically trained for these roles.

Coding, coverage, and compensation for pathology and laboratory medicine services.

Compensation for pathologist and clinical laboratory services generally depends upon standardized procedural coding systems, the coverage determinations of individual insurance companies, fee schedules that assign reimbursement rates for those services, and contractual compensation arrangements. Procedural coding relies primarily on the American Medical Association's Current Procedural Terminology (CPT) nomenclature. Disease conditions, signs, and symptoms are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification. The single largest health insurance "company" in the United States is the Center for Medicare and Medicaid Services (CMS), and most private insurance companies look to CMS as a model for health services compensation. CMS uses a Physician Fee Schedule and a separate Clinical Laboratory Fee Schedule, whose designs and annual updates differ.

Risk management and compliance in pathology and laboratory medicine.

Successful and ethical management of a clinical laboratory requires vigilant focus on proper business conduct. A comprehensive risk management program must encompass government standards as provided for financial and marketing practices, including fraud and abuse, antitrust, antikickback, privacy, and security. The program also must incorporate the appropriate reaction to medical malpractice litigation along with considerations of expert testimony.

Future trends.

Several current forces have set anticipated future changes in health care in motion, or, at least, have set the stage for change. End-consumer demand increasingly drives the market; as a result, entire businesses are transforming or emerging anew to meet these demands. In general, consumers demand high quality at reasonable cost, to be delivered as fast as possible with minimal inconvenience. The health care consumer takes this expectation further, to include the desire for all helpful information regarding one's health to be made readily available for him/her to make the best decision and minimize morbidity, mortality, misdiagnosis, and inconvenience. This article addresses the impact upon the laboratory by considering four key interrelated dynamics that affect these trends: market, medicine, technology, and information systems.

Teaching Laboratory Management Principles and Practices Through Mentorship and Graduated Responsibility: The Assistant Medical Directorship.

With the changing landscape of medicine in general, and pathology in particular, a greater emphasis is being placed on laboratory management as a means of controlling spiraling medical costs and improving health-care efficiency. To meet this challenge, pathology residency programs have begun to incorporate formal laboratory management training into their curricula, using institutional curricula and/or online laboratory management courses offered by professional organizations. At the University of Utah, and its affiliated national reference laboratory, ARUP Laboratories, Inc, interested residents are able to supplement the departmental lecture-based and online laboratory management curriculum by participating in assistant medical directorship programs in one of several pathology subspecialty disciplines. The goals of many of the assistant medical directorship positions include the development of laboratory management skills and competencies. A survey of current and recent assistant medical directorship participants revealed that the assistant medical directorship program serves as an excellent means of improving laboratory management skills, as well as improving performance as a fellow and practicing pathologist.

A limited plasma cell flow cytometry panel with reflex CD138 immunohistochemistry is an optimal workflow process for evaluating plasma cell neoplasms in bone marrow specimens.

OBJECTIVES: To determine the optimal workflow combination of flow cytometry (FC) and immunohistochemistry tests for efficient and cost-effective evaluation of plasma cell (PC) neoplasms (PCNs) in bone marrow (BM) specimens. METHODS: Various workflow combinations of immunohistochemistry and FC for 4,031 BM specimens worked up for PCNs were compared. Turnaround time (TAT), immunohistochemistry usage, technical charges, and addendum/amendment rates were compared between periods to determine the optimal workflow combination. RESULTS: Five distinct workflow periods were identified, with varying combinations of full or limited FC panels for assessing PC clonality and CD138/κ/λ immunohistochemistry for PC quantification. Replacement of full FC with limited FC was associated with significant reductions in TAT and number of immunostains performed per case. Elimination of immunohistochemistry on cases determined to be polyclonal by FC also resulted in significant reductions in immunohistochemistry usage and significant cost savings. CONCLUSIONS: Assessment of PC clonality using a limited FC panel followed by reflex CD138 immunohistochemistry on cases that are monoclonal by FC provides an optimal and cost-effective workflow for evaluating PCNs in BM samples.

Estimating the budgetary impact of setting the medicare clinical laboratory fee schedule at the national limitation amount.

The Institute of Medicine (IOM) of the National Academy of Sciences was commissioned by Congress to study the current system for the payment of diagnostic clinical laboratory services provided to Medicare beneficiaries. The current system was established in 1984 and has grown in complexity and is of diminishing contemporary relevance. The IOM recommended that a single, rational, nationalfee schedule be established and that it be initially based on the National Limitation Amount (NLA) currently mandated as the national fee cap. To estimate the potential budgetary impact of this recommendation, we merged the 1999 Part B Extract and Summary System and the 1999 Clinical Diagnostic Laboratory Fee Schedule (CLFS). By using an estimated 193 million allowed services from this data set and the current mean fee of $9.14 per test, current spending is approximately $1,768 million. The impact of raising the CLFS to the NLA will be approximately $1,792 million, or $9.26 per test. The estimated cumulative budgetary effect, factoring in the current forecast for the Consumer Price Index, is an increase of approximately $993 million over 5 years and $2,359 million over 10 years.

Progress toward improved leadership and management training in pathology.

CONTEXT: Competency gaps in leadership and laboratory management skills continue to exist between what training programs deliver and what recent graduates and future employers expect. A number of recent surveys substantiate this. Interest in delivering content in these areas is challenged by time constraints, the presence of knowledgeable faculty role models, and the necessary importance placed on diagnostic skills development, which overshadows any priority trainees have toward developing these skills. OBJECTIVE: To describe the problem, the near-future horizon, the current solutions, and the recommendations for improving resident training in laboratory management. DATA SOURCES: The demands of new health care delivery models and the value being placed on these skills by the Pathology Milestones and Next Accreditation System initiative of the Accreditation Council for Graduate Medical Education for training programs emphasizes their importance. This initiative includes 6 milestone competencies in laboratory management. Organizations like the American Society for Clinical Pathology, the American Pathology Foundation, the College of American Pathologists, and the Association of Pathology Chairs Program Directors Section recognize these competencies and are working to create new tools for training programs to deploy. CONCLUSIONS: It is our recommendation that (1) every training program develop a formal educational strategy for management training, (2) greater opportunity and visibility be afforded for peer-reviewed publications on management topics in mainstream pathology literature, and (3) pathology milestones-oriented tools be developed to assist program directors and their trainees in developing this necessary knowledge and skills.

The long and winding regulatory road for laboratory-developed tests.

"High complexity" clinical laboratories are approved under the Clinical Laboratory Improvement Amendments to develop, validate, and offer a laboratory-developed test (LDT) for clinical use. The Food and Drug Administration considers LDTs to be medical devices under their regulatory jurisdiction, and that at least certain LDTs should be subject to greater regulatory scrutiny. This review describes the current regulatory framework for LDTs and suggests ways in which to appropriately enhance this framework.

A consensus curriculum for laboratory management training for pathology residents.

Through the combined efforts of the American Pathology Foundation (APF), the American Society for Clinical Pathology (ASCP), and the Program Directors Section (PRODS) of the Association of Pathology Chairs (APC), a needs assessment was performed via a survey on the PRODS listserv, workshops at the APC/PRODS annual meetings in 2009 and 2010, and a Work Group of representatives of APF, ASCP, and PRODS. Residency program needs and resource constraints common to training pathology residents in practice and laboratory management were identified. In addition, a consensus curriculum for management training was created to serve as a resource for residency training program directors and others. The curriculum was converted into a "wiki" design tool for use by program directors, residents, and faculty.