Mi opinion sobre las diferencias entre la acreditación por CAP y por ISO 15189

Estas son algunas de las diferencias que yo veo entre la acreditación de laboratorios clínicos por ISO 15189 y por CAP (considerando que los requerimientos de acreditación de CAP son similares a los de la cláusula 5 de ISO 15189).

[Esta información es proporcionada independientemente del College of American Pathologists (CAP) y consiste solamente ideas del autor que de ninguna manera representan pronunciamientos del CAP] [This information is solely the opinion of Dr. Reichberg and in no way represent any positions or statements by the College of American Pathologists]

1. Los requerimientos de Colegio Americano de Patólogos (College of American Pathologists, CAP) se originan en la comunidad de profesionales de laboratorio que forma parte de los comités de elaboración de las "preguntas de inspección", las que son basadas en evidencia de la literatura, revisadas y ampliadas anualmente. Los criterios de ISO 15189 y sus procesos de actualización cada cinco años son creados por el comité ISO/TC 212 of ANSI

2. Los requerimientos de CAP son articulados en su totalidad en las "preguntas de inspección" que son explícitas, concretas y contienen explicaciones y ejemplos, y que son exactamente las mismas para todos los laboratorios en el mundo. En contraste, los criterios de inspección para ISO dependen de la agencia que maneja la acreditación y pueden variar en grado y expresión de agencia a agencia o de país a país.

3. Generalmente los criterios de ISO 15189 son más abstractos. Para asegurar cobertura por ISO, los laboratorios escriben documentos más extensos que lo necesarios para la acreditación por CAP, cuyos requerimientos son más concretos y literales. La acreditación por CAP se puede asegurar por anticipado simplemente siguiendo al pié de la letra los requerimientos en las preguntas de acreditación. Cualquier duda sobre una pregunta se puede aclarar llamando a un número sin cargo. Preparación para la acreditación por ISO requiere imaginación y esfuerzo para tratar de cubrir las posibles interpretaciones que las versiones locales y los inspectores puedan tener de los requerimientos.

4. La acreditación de CAP sólo puede obtenerse para el laboratorio completo. La acreditación de ISO se puede obtener para una sección del laboratorio, o aún un solo examen. Consideraciones éticas requieren que la cobertura de las acreditaciones sean claramente explicadas en toda oportunidad en que se anuncian, no sólo en el despliegue de los certificados, sino también en los materiales de promoción.

5. Los inspectores de CAP son simplemente colegas que han sido entrenados en las técnicas de inspección y toman uno o dos días de su rol en el laboratorio para inspeccionar un laboratorio de características similares al propio. Todo laboratorio acreditado por CAP debe permitir a sus miembros,tiempo para inspeccionar otros laboratorios para el CAP. El tiempo lo proporciona el laboratorio que inspecciona y los gastos de viaje los paga el CAP. En el caso de ISO, la implementación es llevada a cargo por una variedad de agencias diferentes. Por lo tanto, la constitución del equipo de inspección depende de la agencia y puede incluir miembros dedicados a inspección de laboratorios a tiempo completo.

6. Cualquier duda, consulta o queja de miembros del equipo del laboratorio, los pacientes o los usuarios clínicos, se puede comunicar o aclarar con una simple llamada telefónica al número de teléfono del  CAP desplegado públicamente en el laboratorio mismo (uno de los requerimientos de acreditación). El sistema de quejas es variable en laboratorios acreditados por ISO.

7. En caso de las instituciones que requieren acreditación por la "Joint Commission" (JC) para tratar pacientes que residen en los EEUU, la acreditación del laboratorio por CAP es suficiente y no necesitan una inspección del laboratorio por la JC. En general, laboratorios acreditados por CAP pueden obtener certificación bajo la ley de laboratorios clínicos de los EEUU (CLIA) sin una inspección adicional.

8. En laboratorios fuera de los EEUU, la acreditación por ISO no requiere el uso de servicios de control externo (proficiencia) específicos. El CAP exige el uso de su programa de control externo. Ese requerimiento comprueba constantemente que el laboratorio se mantiene a un nivel de calidad analítica comparable con otros laboratorios acreditados en el mundo entero.

9. Mientras los requerimientos de auto-inspección varían en las diferentes encarnaciones de ISO, el CAP requiere que la mitad de las inspecciones anuales sean hechas por el equipo del laboratorio mismo, siguiendo las mismas pautas (preguntas y otros componentes de inspección) que usan los colegas-inspectores externos en los años alternantes.

10. En general, la cultura de la acreditación de CAP persigue el objetivo de mejorar la calidad del servicio a través del mejoramiento paulatino y permanente de las prácticas y del nivel profesional del equipo del laboratorio. Esto contrasta con la filosofía de otras acreditaciones que se basan en reducir en número de violaciones y, a menudo, se llevan a cabo por inspectores profesionales que pueden no tener experiencia reciente de haber trabajado en laboratorios.

11. El CAP ofrece programas para la acreditación de CAP y también para ISO 15189 (la acreditación CAP es requerimiento previo para la acreditación ISO otorgada por el CAP). Otras agencias que acreditan para ISO, no proporcionan la opción de acreditación por CAP.

First CAP clinical laboratory accreditation in Chile

What does it take for a laboratory without any experience with, or neighbors who know anything about, the College of American Pathologists (CAP) accreditation and whose staff is not fluent in English, to obtain CAP accreditation?

The Specialty Clinical Laboratory at Clínica Dávila Hospital in Santiago, Chile received its College of American Pathologists (CAP) accreditation last December 11th, the first full-service clinical laboratory ever to be so accredited in Chile.

It was no small task, considering the language and cultural environment. Carlos Vega MT, the Administrative and Technical Director, drove this initiative despite the absence of a professional with knowledge of CAP accreditation in the country with whom to consult, and despite significant language barriers (CAP accreditation questions do not have an official Spanish translation). In addition, during 2018, while preparing for the accrediting inspection, the lab endured a hospital-wide 45-day strike, changed its chemistry instrumentation from Ortho to Roche, its middleware, its laboratory information system (LIS), its quality management data system and its laboratory Quality Manager, who left to join a commercial firm.

Despite these odds, the Clínica Dávila Specialty laboratory prevailed due to the strong culture and tradition of quality championed for years by Mr. Vega, an impressively competent staff and a strong resolve.

Carlos Vega (third from right), Dr. Cecilia Tapia, Laboratory Director (second from left) and some of the laboratory leaders preparing for the CAP inspection in April 2018

I am fortunate to have worked with this impressive group of laboratory professionals, personally during trips in April and September 2018, and remotely during the year, helping them translate their solid culture of quality into practices that are familiar to me. While language represented a barrier to some, it was the ability to internalize the pragmatic and rather literal style of quality that I practice in New York that underlies their success. 

The Dávila laboratory was already ISO 15189 accredited and, after a professional absence of more than four decades, I struggled with the extensive documents the laboratory had created to achieve that accreditation and with the rather philosophical emphasis on general principles and concepts prevalent in my native country of poets. It took many repetitions until they understood that the detailed requirements in the CAP accreditation questions meant exactly what was written. No more, no less. Much of the changes in documents consisted in trimming them down and in the simple measure of making them instantly available.

I will summarize my impression of the general differences between CAP and ISO 15189 accreditation in my next blog.

Updated cholesterol testing guidelines

Updated guidelines blood (plasma and serum) cholesterol laboratory testing were published this month (1) by two European societies (2).

While upholding the central importance of the Low Density Lipoprotein cholesterol (LDLC) fraction, they extend the focus to the important role of the LDL protein component, apolipoprotein B (“apoB”), to an additional cholesterol fraction: the triglyceride (“TG”, fat) -associated cholesterol (remnant particles, “Remnant-C”) and to Lipoprotein(a) (“Lp(a)”).

This expanded view was motivated by the impact of new effective treatments that drastically lower LDLC and by the increased prevalence of diabetes and metabolic syndrome. It translates into the consensus-based recommendations transliterated in this glossary table:

- Follow-up of lipid profiles of a patient, from baseline at diagnosis to on-treatment measurements, should be ideally performed with the same assay method (and preferably the same laboratory and instrument).

- Laboratories..should report lipid profiles with declaration of the assay method/manufacturer used.

- Values near the treatment decision cutoffs should be confirmed by ≥ 2 repeated measurements by the same method and then averaged.

- Comprehensive assay(s) of atherogenic lipoproteins should not only assess the risk conferred by LDL particles, but also by remnant particles, and Lp(a).

- When LDLC is unavailable because of an invalid Friedewald equation (TG ≥ 400 mg/dL), calculation of non-High Density Lipoprotein Cholesterol (non-HDLC) should be used instead of direct LDLC. Non-HDLC can be calculated in the fasting and non-fasting state, independent of TG variability and also includes an estimate of Remnant-C.

- LDLC continues to be the primary target of lipid-lowering therapy. But, when LDLC goal is achieved, then non-HDLC or apoB should be preferred as secondary treatment targets in patients with triglycerides (TG) ≥ 175 mg/dL, obesity, metabolic syndrome, or type 2 diabetes.

- The ApoB assay can estimate LDLP (95% of apoB) plus Remnant-P and Lp(a) particle numbers in the fasting and non-fasting state.

- The Lp(a)-corrected LDLC should be assessed at least once if the patient shows a poor response to LDL-lowering therapy or in patients with suspected or known high Lp(a).

(1) Langlois, M. R. and 21 other authors. Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM. Clinical Chemistry 64, 1006–1033 (2018).

(2) European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative

School closures

It turns out that I have not been alone in wondering about what to do if school children or staff appear to have the flu. The death of Mitchell Wiener, assistant principal at Intermediate School 238 here in New York City (NYC), sparked a wave of concern and much debate on when to close schools. NYC Health Commissioner (and soon-to-be head of the CDC), Dr. Frieden and school Chancellor Klein posted criteria that the city will use to close affected schools, following CDC's own guidelines. But these measures have not reduced the concerns as fear spreads faster than the virus.

As previously mentioned, the dilemma of whether or not to close a school would be greatly alleviated if a fast (overnight turnaround) accurate test was available. The majority of disease clusters will turn out not to be due to the swine flu virus. Conversely, true swine flu cases could be identified before the infection spreads within the school (hopefully, even before the child has attended school).

Is that test necessary?: blood cultures in pneumonia

In response to a question in the American Society of Microbiology laboratory discussion group (DivC), I sent this message:

In fact, as Dr. Manasse suspects, blood cultures are the subject of the Joint Commission Core Measure PN-3b.

However, careful examination of the measure does not justify the use of blood culture tests in all Emergency Department patients with pneumonia.

Core Measure PN-3b "Blood Cultures Performed in the Emergency Department Prior to Initial Antibiotic Received in Hospital" is described at:
http://manual.jointcommission.org/bin/view/Manual/MIF0006

As you can see there, the measure is justified by "Published pneumonia treatment guidelines recommend performance of blood cultures for all inpatients to optimize therapy" and lists several published guidelines. The most recent citation is:

Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin. Infect. Dis. 2007;44 Suppl 2:S27-72
(http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=10560)

Mandell et al. write that "Recommendations for diagnostic testing remain controversial. The overall low yield and infrequent positive impact on clinical care argue against the routine use of common tests, such as blood and sputum cultures", however they add that "cultures may have a major impact on the care of an individual patient" and identify the individual patients for whom "pretreatment blood samples for culture...should be obtained" as those with:

• Intensive care unit admission
• Cavitary infiltrates
• Leukopenia
• Active alcohol abuse
• Chronic severe liver disease
• Asplenia (anatomic or functional)
• Positive pneumococcal Urinary Antigen Test result
• Pleural effusion

(Table 5 and Recommendation # 12)

Severe pneumonia that justifies blood culture testing, in addition to the criteria above, also includes patients with three or more of the following "minor" criteria:

• Respiratory rate >=30 breaths/min
• PaO2/FiO2 ratio =<250 li="">
• Multilobar infiltrates
• Confusion/disorientation
• Uremia (BUN level, >=20 mg/dL)
• Hypothermia (core temperature, <36>
• Thrombocytopenia (platelet count, <100>
• Hypotension requiring aggressive fluid resuscitation
• Hypoglycemia (in nondiabetic patients)
• Hyponatremia
• Unexplained metabolic acidosis or elevated lactate level

For the rest of patients with less severe pneumonia, recommendation #11 applies: "Routine diagnostic tests to identify an etiologic diagnosis are optional for outpatients with Community Acquired Pneumonia".

Thus, Denise Jones' Emergency Department (ED) physicians are only 33.3% correct in requesting blood cultures in patients with low oxygen saturation, since hypoxia should be accompanied by two other minor criteria to justify the test, according to the authorities cited by the Joint Commission.

The criteria listed above require a basic patient assessment that can be completed quickly in the ED (problem-oriented patient history, measurement of blood pressure, temperature and respiration rate, chest x-ray, CBC, urine antigen tests and serum metabolic profile plus alcohol and lactic acid levels) so that they will only slightly delay administration of antibiotics.

For these reasons, and armed with the information above, the laboratory could argue convincingly against the need to obtain a sample before deciding whether a blood culture will be needed.

In addition to the unnecessary work imposed on usually overwhelmed ED and laboratory staffs, the invasive nature of the procedure and the cost of supplies and equipment, there is the problem of false negatives: in samples kept at room temperature, some organisms might grow to exceed the CO2 detection threshold so that their presence will not be detected by the continuous CO2 monitoring system when they are eventually placed in the blood culture incubator. BioMérieux sent a BacT/Alert system notification to that effect a couple of years ago.

False positive results could also be more frequent under these circumstances. I have noticed that often, blood culture contamination rates are higher in the ED than in in-patient services (is that also your experience?) and I wonder whether sterility precautions are observed as scrupulously when the person drawing the sample is not sure that it will, in fact, be used.

We are all compelled to avoid waste and error in health care, especially now that the prospect of real reform is on the horizon. Laboratory efforts to fine-tune accreditation demands so that they make sense, are a valuable contribution. Denise: go ahead and fight that battle using the information above.

In preparation for the Fall

As the number of confirmed cases seems to be decreasing (as shown by the May 4th CDC figure) and severity appears not to exceed that of seasonal influenza, public attention to the 2009 H1N1 flu wanes. Laboratorian's attention should not: as mentioned earlier, parallels with the 1918 pandemic predict worse outbreaks in the Fall. In my opinion, the following laboratory diagnostic tools should be in place in the U.S. by then: (1) a sensitive molecular test for virus detection and (2) a specific serum/plasma antibody test for retroactive diagnosis.

The CDC developed the amplified RNA test in an amazingly short time. However, it has been limited to local Public Health laboratories. Despite those laboratories' heroic efforts, this limitation precludes its widespread use. The first test offered outside Public Health labs, was only made available by Quest Diagnostics two days ago. However, this test is only offered in one location in the U.S. and still requires confirmation by local Public Health laboratories. Further, important details of sample collection and estimates for the clinical sensitivity of the molecular test are not yet available.

I was personally involved in two potential school events which begged a rapid sensitive test. I described the first experience below (another teacher in that school's district has since been confirmed as suffering from the swine flu). Last Friday, I was asked advice in a third-grade incidence, where six out of 30 students in a single classroom in a school in New York City fell ill with suggestive symptoms. On Monday half of the students in the class, including five of the six, were absent. The symptoms (fever, malaise, headache, muscle aches) of the sixth, a nine year old girl whose pediatrician prescribed Tamiflu (oseltamivir) on Saturday, resolved within hours of starting treatment. Today, a week later, most of the sick children have returned, and the whole class is visiting the local Zoo. If the incident was, in fact, due to the flu, this group of students has disseminated the virus widely. Had one of the sick students been tested within the first day and found to host the H1N1 virus, the school might have decided to take containing measures, including possible closure, despite the CDC advise of not to close "unless there is a magnitude of faculty or student absenteeism that interferes with the school's ... ability to function."

While we should no longer worry that the children who fell ill last week could spread the virus, others in the incubation phase of this potential H1N1 outbreak, might. In this scenario, the finding of specific antibodies in the blood of convalescent students, could help with containment efforts and in the diagnosis of contacts. Such antibody test would also be used as an important epidemiological tool.

Method and sample collection for the '09 H1N1 confirmation test

Dan Jernigan from the CDC is quoted by GenomeWeb, as informing that the CDC's rRT-PCR Swine Flu Panel has been distributed to 78 qualified labs throughout all 50 states in the US, as well as labs in 130 countries, and 10 Department of Defense labs in the US. Because of the shortage of reagents, the CDC is working with other vendors to get new molecular assays cleared.

The current CDC rRT-PCR test uses TaqMan probes designed by the CDC and is run on Applied Biosystems' 7500 Fast Dx Real-Time PCR instrument (the brochure is a 31.4Mb download). Last October, this instrument/CDC rRT-PCR Flu Panel combination received 510(k) clearance for sub-typing of influenza viruses in qualified laboratories.

The "flocked swab" recommended for sample collection is explained in Copan's web site, which also offers a Twit, a set of video instructions and an animation explaining nasopharingeal sample collection.

Dr. E. J. Baron, Director of the Clinical Microbiology and Virology Laboratories at Stanford U. Med. Center, informed that these Copan swabs are available from Copan (Cat # 503CS01), Becton Dickinson (Cat # 220252) and Diagnostic Hybrids (which offers several configurations).