Professional Documents
Culture Documents
Informe de Evaluacin de
Tecnologas Sanitarias N 53
Madrid. Diciembre de 2007
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N.I.P.O.: 354-07-049-6
I.S.B.N.: 97-88495463-49-4
Depsito Legal: M-10809-2008
2 Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007
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D i r e c c i n A E T S:
Antonio Sarra Santamera
Autores:
Luis M. Plaza Gmez
Armando Albert Martnez
IEDCYT-CSIC
Instituto de Estudios Documentales sobre Ciencia y Tecnologa
Consejo Superior de Investigaciones Cientficas
Edicin y difusin:
Antonio Hernndez Torres
Versin espaola de los Drs. Luis M. Plaza y A. Albert, del IEDCYT-CSIC (Instituto de Estudios
Documentales sobre Ciencia y Tecnologa - Consejo Superior de Investigaciones Cientficas) al
amparo del Proyecto PI06/90621 de la Convocatoria de Evaluacin de Tecnologas Sanitarias del
Instituto de Salud Carlos III.
Publicacin sin nimo de lucro. El precio del presente ejemplar corresponde al ejemplar en
papel. El texto ntegro se difundir gratuitamente en versin electrnica desde la pgina web
de la Agencia de Evaluacin de Tecnologas Sanitarias del Instituto de Salud Carlos III.
Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007 3
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EDICIN BILINGE
El presente volumen comprende sendas versiones de las Directrices de la OECD para garanti-
zar la calidad de los estudios genticos moleculares. Tras la versin espaola, en traduccin
autorizada pero no oficial, figura la versin original en ingls conforme a la publicacin oficial
de la OECD.
Distribucin: Pg.
D I R E C T R I C E S D E L A O E C D P A R A G A R A N T I Z A R L A C A L ID A D D E L O S
ESTUDIOS GENTICOS MOLECULARES ................................................... 5
O E C D G U ID E L I N E S F O R Q U A L I T Y A S S U R A N C E I N M O L E C U L A R
GENETIC TESTING ................................................................................. 39
4 Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007
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ndice
DIRECTRICES DE LA OECD PARA GARANTIZAR LA CALIDAD DE LOS ESTUDIOS
GENTICOS M O L E C U L A R E S
Pg.
P r e f a c i o d e l a v e r s i n e s p a o l a ................................................................................ 10
A n t e c e d e n t e s ................................................................................................................. 12
Prlogo .......................................................................................................................... 14
1. Alcance ...................................................................................................................... 19
2. Principios y buenas prcticas 20
A. Principios generales y buenas prcticas para los estudios genticos moleculares 20
B. Sistemas para garantizar la calidad en estudios genticos moleculares .............. 20
C. Controles de competencia: vigilancia de la calidad en la actuacin de los
laboratorios ........................................................................................................ 21
D. Garantizar la calidad en la comunicacin de los resultados de los estudios
genticos moleculares ........................................................................................ 22
E. Nivel de estudios y formacin del personal de laboratorio .................................. 23
P a r t e I I . A n o t a c i o n e s ................................................................................................. 25
Introduccin .............................................................................................................. 27
Terminologa general................................................................................................. 28
1. Principios generales y buenas prcticas para los estudios genticos moleculares 29
2. Sistemas para garantizar la calidad en estudios genticos moleculares .............. 31
3. Controles de competencia: vigilancia de la calidad en la actuacin de los
laboratorios ........................................................................................................ 33
4. Garantizar la calidad en la comunicacin de los resultados de los estudios
genticos moleculares ........................................................................................ 35
5. Nivel de educacin de estudios y formacin del personal de laboratorio ............. 36
G l o s a r i o ......................................................................................................................... 38
Nota: Esta versin al espaol del documento original en ingls ha sido realizada en el Centro de Informacin y
Documentacin Cientfica (CINDOC) del Consejo Superior de Investigaciones Cientficas (CSIC) de Espaa, bajo la
supervisin del Prof. Armando Albert, representante espaol en el Grupo de Trabajo en Biotecnologa (WPB) de la
OECD dentro del proyecto de investigacin PI06/90621 de la convocatoria de Evaluacin de Tecnologas
Sanitarias del Instituto de Salud Carlos III.
Se ha empleado la terminologa mdica de uso ms comn entre los profesionales y directores de laboratorios de
estudios genticos moleculares espaoles.
Madrid, Julio de 2007.
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Resumen
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TITLE: OECD Guidelines for Quality Assurance other OECD member countries and, as was the
in Molecular Genetic Testing (Spanish Version) case in some of them, the absence of specific
legislation to regulate basic aspects of molec-
A u t h o r s : Armando Albert Martnez, Luis M. ular genetic testing performed for medical
Plaza Gmez. Agency: IEDCYT- CSIC/ AETS purposes was evident.
(Instituto de Estudios Documentales sobre
Ciencia y Tecnologa- Consejo Superior de Inves- M e t h o d o l o g y D a t a S o u r c e s : The need to
tigaciones Cientficas / Agencia de Evaluacin de harmonise the international situation was
Tecnologas Sanitarias) (Institute of Documental endorsed by the OECD Committee for Scientific
Studies on Science and Technology - Spanish and Technological Policy meeting at ministerial
National Research Council / Spanish Health level as well as by OECD member country
Technology Assesment Agency). Health Ministers who together decided the
C o n t a c t : Armando Albert/ Jose M Amate OECD countries should develop Recommen-
Blanco D a t e : December 2007 P a g e s : 64 dation on Quality Assurance in Molecular
P r i c e : 10 L a n g u a g e : Spanish and English. Genetic Testing finally adopted by the OECD
E n g l i s h a b s t r a c t: Yes I S B N 97-88495463- Council on 10 of May 2007, which sets out a
49-4 Technology: Molecular Genetic Testing. number of principles and best practices
MeSH keywords Biomedical. Other keywords: relevant to this field of activity, that were
Molecular Genetic Testing, Spanish Labo- previously studied and discussed in detail in
ratory Directory, Survey Analysis. the Working Party on Biotechnology including
an open consultation with interested parties.
P u r p o s e of t h e A s s e s s m e n t O b j e c t i v e : The Recommendation aims to contribute to
About 100.000 Molecular Genetic Tests (MGT) the development and implementation of regu-
are carried out in Spain every year, in more lations and procedures to assure the quality of
than one hundred laboratories, most of which the MGT, the comparability of techniques and
(80%) are located in university hospitals in the results and international cooperation in this
Public Health System, and the remaining 20% field amongst the OECD member and non
of which are private laboratories, as it is member countries.
reported in the Directory of Spanish Molecular
Genetic Testing Laboratories, published at C o n t e n t o f t h e r e p o r t / R e s u l t s : The
the end of 2004 by the Spanish Agency for approved Recommendation has been published
Evaluation of Health Technologies of the as the OECD Guidelines for Quality Assur-
Instituto de Salud Carlos III. That publication ance in Molecular Genetic Testing in its
also included the information collected from original version in English, describing in
an OECD survey to document the availability detail Principles, that are policy recommen-da-
and extent of molecular genetic testing in the tions to governments and those involved in
member countries, that was conducted in the the regulation of genetic services, and Best
case of Spain, under the supervision of Prof. Practices aimed at professional associations
Armando Albert and Dr. Luis M. Plaza in and others involved in the provision of
the Centre for Scientific Information and molecular genetic testing and Annotations
Documentation (CINDOC) of the Spanish Sci- providing additional information on the
entific Research Council (CSIC) as part of contents of the principles and best practices.
a research project financed by the Instituto
de Salud Carlos III. Main Survey Results: To facilitate diffusion
The results of the10survey showed that the of the Guidelines to a wide range of professionals
Spanish situation regarding aspects related to involved in the MGT and its quality assurance
the availability and quality assurance of the in our country, a Spanish version of the
MGT was similar to that observed in many said Guidelines has been prepared with the
8 Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007
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purpose of making it also available for diffusion to of a Meeting of Experts to discuss and elaborate,
other Spanish speaking countries interested in jointly with all the parties involved in producing
knowing and implementing them. MGT, a report on the most appropriate proposals
that might be made to the authorities of the
Recommendations / Conclusions: The diffu- Spanish Ministry of Health in order to implement
sion of the Guidelines in our country is also the guidelines in our country and produce the
intended as a step preliminary to the organisation necessary changes in legislation.
Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007 9
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Armando Albert
Luis M. Plaza
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pases de lengua espaola que estn intere- Todas estas actividades se estn llevando a
sados en difundir y aplicar su contenido. cabo en el marco del proyecto de investigacin
PI06/90621, financiado por el Instituto de
Esta difusin en nuestro pas pretende Salud Carlos III del Ministerio de Sanidad y
adems servir de fase previa a la organizacin Consumo, a un grupo de trabajo del CINDOC
de una reunin de expertos, que permita del CSIC, bajo la supervisin del Prof.
elaborar conjuntamente con las partes ms Armando Albert y el Dr. Luis M. Plaza y en
directamente implicadas en la realizacin colaboracin con el Dr. Jos Maria Amate y la
de los EGM, un informe sobre las mejores Dra. Saz Parkinson, de la Agencia de Evalu-
soluciones y propuestas a las autoridades acin de Tecnologas Sanitarias.
sanitarias para la implementacin de las La presente publicacin bilinge de las
Directrices en nuestro pas, y la revisin de Directrices, que se hace sin nimo de lucro,
los aspectos legales necesarios al efecto. cuenta con la autorizacin de la OECD.
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Antecedentes
1
Estudios Genticos: Aspectos Polticos para el Nuevo Milenio, (2000) OECD.
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Dado que los laboratorios prestan cada vez ms clnicos, consultando a expertos y a las partes
servicios, tanto a clientes nacionales como inter- interesadas. Este trabajo llev a la Recomen-
nacionales, existe la necesidad de desarrollar un dacin para Garantizar la Calidad en
consenso internacional y unas buenas prcticas Estudios Genticos Moleculares adoptada por
para garantizar la coherencia de la calidad de los el Consejo de la OECD el 10 de mayo de 2007
servicios disponibles. que establece, inter alia, una serie de princip-
ios y buenas prcticas pertinentes a este
La necesidad de llevar a cabo medidas interna- campo de actividad. Los Principios son re-
cionales para resolver estas cuestiones fue comendaciones de poltica especialmente diri-
respaldada por el Comit de Poltica Cientfica gidas a los Gobiernos y a las personas
y Tecnolgica de la OECD en su reunin de implicadas en la regulacin de los servicios
enero de 2004 as como por los ministros de genticos. Las Buenas Prcticas son recomen-
sanidad de la OECD en su reunin de mayo de daciones que pretenden proporcionar un as-
2004. Los pases miembros de la OECD esoramiento operativo para implementar los
acordaron, por lo tanto, desarrollar unas Principios y estn dirigidas a los organismos
directrices que establezcan los principios y las profesionales y a los proveedores de servicios
buenas prcticas para garantizar la calidad en de estudios genticos moleculares en pases
los estudios genticos moleculares con fines con economas desarrolladas y en desarrollo.
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Prlogo
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Parte I.
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1. Alcance
Esta Recomendacin se aplica para garantizar o dolencia concreta y en los estudios genti-
la calidad de los estudios genticos molecu- cos predictivos realizados a menudo antes
lares realizados en un contexto clnico. Se de que surjan signos clnicos de la enfer-
aplica a los estudios genticos para varia- medad o dolencia. Es relevante para los
ciones en las secuencias de ADN de la lnea estudios de las variantes de ADN heredi-
germinal, o a los productos que surgen tarias que predicen el perfil de respuesta de
directamente de cambios en las secuencias un individuo a un medicamento o terapia y
genmicas hereditarias, que predicen efectos que influyen en la susceptibilidad de padecer
sobre la salud, o que influyen en el cuidado una enfermedad, en el pronstico del
de la salud, de un individuo. paciente, el asesoramiento, el tratamiento y
la planificacin familiar. No se aplica a los
Se centra en los estudios genticos molecu- estudios realizados nicamente con fines de
lares para el diagnstico de una enfermedad investigacin.
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B.3 La acreditacin u otro reconocimiento B.iii Los asesores tcnicos que acten en nombre
equivalente deben basarse en estndares y de organismos de acreditacin o de organismos
directrices reconocidas a nivel internacional, que proporcionen un reconocimiento equiva-
para facilitar el reconocimiento mutuo de los lente deben contar con las cualificaciones,
servicios de estudios genticos moleculares. formacin y experiencia pertinentes a los
estudios genticos moleculares.
B.4 Los requisitos adoptados por los organismos
legales, reglamentarios y profesionales para que B.iv Los laboratorios deben contar con polticas
los laboratorios sean reconocidos como compe- y procedimientos para documentar la validez
tentes a travs de una acreditacin o de un re- analtica de todos los estudios realizados.
conocimiento equivalente, deben ser accesibles,
estar redactados de forma clara y eficaz. B.v Los laboratorios deben contar con polticas
y procedimientos para evaluar peridicamente las
B.5 Se deben introducir normativas e incentivos medidas internas de control de calidad y para
para facilitar el desarrollo y la implementacin documentar los hallazgos y cualesquiera medidas
de una acreditacin o reconocimiento equivalente. correctivas tomadas para tratar las deficiencias.
B.6 Se deben identificar y resolver los imped- B.vi Los laboratorios deben poner a disposicin
imentos para cumplir los requisitos de acred- de los usuarios del servicio pruebas recientes
itacin u otro reconocimiento equivalente. relativas a la validez y utilidad clnica de los
estudios que ofrecen.
B.7 Los gobiernos y/o los organismos
reglamentarios deben garantizar que existan B.vii Los operadores de I+D, los fabricantes,
sistemas para controlar y tratar los casos en los profesionales de la sanidad y los laboratorios,
los que los laboratorios no cumplan con los as como otros grupos pertinentes, deben co-
requisitos para garantizar la calidad. laborar para establecer la validez y la utilidad
clnica de los estudios, especialmente para las
B.8 Los gobiernos deben fomentar la colabo- enfermedades raras o de baja prevalencia.
racin internacional para el desarrollo, la
verificacin, la disponibilidad y el uso de B.viii Los laboratorios deben cooperar con las
materiales de referencia para los estudios instituciones nacionales e internacionales
genticos moleculares. pertinentes para recoger, desarrollar, verificar
y poner a disposicin, materiales de referen-
B.9 Los gobiernos deben fomentar la colabo- cia para estudios genticos moleculares.
racin internacional para el desarrollo y la vali-
dacin de los estudios genticos moleculares. B.ix Los laboratorios deben utilizar los materi-
ales de referencia disponibles y/o controles de
mutacin especficos de la familia (privados)
Buenas Prcticas cuando sea apropiado y estn disponibles.
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C.2 Los gobiernos, los organismos reglamen- C.v Los laboratorios deben participar en un
tarios y profesionales deben respaldar la programa de estudio de aptitud para cada
disponibilidad de y el acceso a controles de enfermedad para la que realizan un estudio,
competencia. cuando dichos programas estn disponibles.
Cuando no estn disponibles, deben participar
C.3 Los proveedores de programas de controles en mtodos alternativos relevantes o perti-
de competencia deben ser competentes para nentes para los estudios que realizan.
proporcionar dichos programas, tal y como se
establezca por una acreditacin o re- C.vi Los laboratorios deben poner en
conocimiento equivalente. conocimiento del publico el hecho de que par-
ticipan en controles de competencia.
C.4 La acreditacin o el reconocimiento
equivalente debe ser la base para el re- C.vii La actuacin individual de un laboratorio
conocimiento internacional de los proveedores en programas de controles de competencia
de programas de controles de competencia. podr publicarse de forma voluntaria por el
laboratorio implicado, pero no ser puesto en
C.5 Los gobiernos, los organismos reglamen- conocimiento del pblico por los proveedores
tarios y profesionales deben tomar medidas de programas de controles de competencia a
para fomentar que los laboratorios participen menos que sea requerido por la ley.
en programas de controles de competencia
acreditados o, cuando no estn disponibles,
para que utilicen mtodos alternativos para
evaluar la calidad de los estudios que realizan. D. Calidad de la
C.6 Deben existir sistemas para controlar la
comunicacin de
actuacin de los laboratorios y para tratar las resultados
actuaciones de baja calidad persistentes.
Principios
Buenas Prcticas D.1 Todos los laboratorios deben emitir los re-
sultados de los estudios genticos moleculares
C.i Los proveedores de controles de compe- en forma de un informe por escrito o elec-
tencia y los organismos profesionales deben trnico al mdico o profesional sanitario que
colaborar para establecer niveles de actuacin lo solicit.
aceptables para los laboratorios que ofrecen
estudios genticos moleculares. D.2 En las jurisdicciones en las que los
informes se puedan enviar directamente a
C.ii Los organismos reglamentarios y profe- los pacientes, los gobiernos y los organismos
sionales responsables del control de la activi- reglamentarios y profesionales deben fomen-
dad de los laboratorios deben identificar la tar que todos los laboratorios que realizan
baja calidad persistente contrastndola con estudios genticos moleculares clnicos re-
normas acordadas y garantizar que se toman comienden a los pacientes que consulten con
oportunamente medidas correctivas y que stas un mdico o profesional sanitario para que les
se documentan. ayuden a comprender las implicaciones del
resultado del estudio.
C.iii Los programas de controles de competen-
cia se deben estructurar para evaluar todas las D.3 Los gobiernos y los reguladores deben
fases del proceso de laboratorio, incluida la requerir que en la emisin y el archivo de
comunicacin de los resultados. informes, todos los laboratorios cumplan la ley
y las normativas aplicables, incluyendo las
C.iv Los proveedores de controles de compe- relativas a la confidencialidad de la informacin.
tencia deben desarrollar y modificar los progra-
mas de controles de competencia para tener en D.4 La interpretacin de los resultados de los es-
cuenta la evolucin de los mtodos analticos. tudios genticos moleculares debe ser apropiada
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D.ii Los informes deben emitirse sin retrasos, 8. El resultado del estudio.
ser precisos, concisos, exhaustivos y deben
comunicar toda la informacin esencial para 9. Una interpretacin del resultado en el
permitir una toma de decisin efectiva por parte contexto del motivo para la realizacin
de los pacientes y de los profesionales sanitarios. del estudio y toda la dems infor-
macin proporcionada al laboratorio.
D.iii Los informes deben utilizar una termi-
nologa y nomenclatura aceptadas interna- 10.La identidad del individuo que aprueba
cionalmente incluyendo la identificacin de las el informe.
secuencias de referencia.
11.La informacin de contacto del laboratorio.
D.iv Los laboratorios deben informar a los
usuarios de sus servicios, sobre la informacin 12.La fecha de emisin del informe.
del paciente y de la familia que el laboratorio
requiere para garantizar la validez de la peticin D.vii Cuando sea oportuno, el informe tambin
del estudio solicitado y para interpretar los debe incluir la siguiente informacin:
resultados.
1. Una recomendacin para asesora-
D.v En las jurisdicciones en las que se permite a miento gentico por parte de un
los laboratorios introducir los informes emitidos profesional sanitario cualificado.
en un historial convencional o electrnico del
paciente, debern incluir en los mismos todos los 2. Las implicaciones para otros miembros
elementos esenciales y relevantes. de la familia.
D.vi Los informes deben incluir como mnimo 3. Recomendaciones para estudios de
la siguiente informacin: seguimiento.
1. Una identificacin que de forma D.viii Todos los elementos esenciales y relevantes
inequvoca vincule el informe al paciente. de los resultados del estudio y de la interpre-
tacin comunicados por un laboratorio de refe-
2. El nombre del profesional sanitario rencia se deben incluir en el informe que se enva
que lo solicit y la informacin de al profesional sanitario que solicit el estudio.
contacto.
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cumplan los estndares o niveles reconocidos, deben ser comparables a las aplicadas en otras
respaldadas por los estudios y la formacin, que reas de la medicina de laboratorio. Deben
garanticen la competencia del laboratorio en la incluir sistemas para validar los requisitos de
realizacin de estudios genticos moleculares. nivel de estudios, formacin, cualificaciones
y habilidades especficas para los estudios
E.2 Las normas para la acreditacin del labo- genticos moleculares.
ratorio u otro reconocimiento equivalente
deben requerir que todo el personal tenga una E.ii Se deben establecer niveles apropiados de
combinacin de estudios, formacin, habili- cualificaciones, estudios y formacin especial-
dades y experiencia que garantice su compe- izada para los individuos que dirigen labora-
tencia. torios de gentica molecular. La cualificacin
mnima requerida para dirigir un laboratorio
E.3 La educacin especializada y los programas debe ser la de Licenciado en Medicina o Doctor
de formacin existentes pertinentes a los es- o una cualificacin equivalente reconocida.
tudios genticos moleculares que cumplan los Los requisitos educativos deben incluir una
niveles reconocidos, deben ser adoptados formacin formal en gentica molecular y
formalmente por los gobiernos y/o los organis- cuando est disponible, una certificacin en la
mos reglamentarios y profesionales. especialidad de gentica molecular de labora-
torio clnico, u otra disciplina equivalente.
E.4 Se debe fomentar el desarrollo de programas
educativos y de formacin cuando stos no existan. E.iii Los directores de laboratorio deben
garantizar que todo el personal de laboratorio
E.5 Las autoridades gubernamentales o profe- tenga la formacin pertinente y que su compe-
sionales pertinentes deben reconocer la tencia se haya documentado antes de realizar
gentica mdica como una disciplina que estudios genticos moleculares con el objetivo
comprende tanto una especialidad clnica de comunicar un resultado de diagnstico
como de laboratorio. sobre cualquier material de paciente.
E.6 Cuando los gobiernos, los reguladores E.iv La educacin y la formacin en gentica
y los organismos profesionales reconozcan debe ser reconocida por organismos reglamen-
cualificaciones mdicas y cientficas otorgadas tarios y/o profesionales como un elemento esen-
por instituciones extranjeras, dicho re- cial para fortalecer la competencia profesional
conocimiento se debe ampliar, segn sea para realizar estudios genticos moleculares.
apropiado, a las cualificaciones equivalentes
sobre estudios genticos moleculares. E.v Los directores de laboratorio deben garan-
tizar que todo el personal implicado en estu-
E.7 Todo el personal implicado en estudios dios genticos moleculares participa en
genticos moleculares debe actuar en el marco programas de educacin y de formacin con-
formado por las normas legales, ticas y tinuada, apropiados para sus funciones y dis-
estndares profesionales. eados para ampliar y mantener de forma
adicional su competencia.
24 Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007
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Parte II.
Anotaciones
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Introduccin
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Terminologa general
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16. Los Principios especifican que todos los usos secundarios y los procedimientos para
servicios de estudios genticos deben estar proteger la confidencialidad (codificacin/elimi-
sujetos a un marco de garanta de la calidad. nacin de identificacin). Algunas recomenda-
En este contexto, un marco se considera como ciones y declaraciones internacionales relevantes
la totalidad de los mecanismos que de forma sobre el consentimiento informado son la
directa o indirecta afectan a la calidad del ser- Declaracin Universal sobre el Genoma
vicio de un laboratorio. stos pueden incluir Humano y los Derechos Humanos (UNESCO
mecanismos reglamentarios, no reglamentarios, 1997), la Declaracin Universal sobre Datos
reguladores y/o profesionales como cdigos de Genticos Humanos (UNESCO 2003) y la
prcticas y directrices clnicas. (A.3) Declaracin Universal sobre Biotica y Dere-
chos Humanos (UNESCO 2005). (A.4)
17. Un proceso que conduzca a un consen-
timiento informado es un paso necesario para 18. Junto con la oferta de un estudio
los procedimientos mdicos, incluyendo los gentico, un profesional sanitario debe tener
estudios genticos moleculares y es la respon- en cuenta la necesidad de un asesoramiento pre-
sabilidad de los profesionales sanitarios. Se vio y posterior al estudio gentico. Para el ob-
reconocen excepciones en la normativa, la ley jeto de estas Directrices, el asesoramiento
y las directrices profesionales. En estas Direc- gentico es el proceso de ayudar a las personas
trices el consentimiento informado se entiende a comprender y a adaptarse a las implicaciones
como una salvaguarda para garantizar la mdicas, psicolgicas y familiares de las
autonoma del paciente y para proporcionarle contribuciones genticas a la enfermedad.
una oportunidad de aprender y comprender la Este proceso integra lo siguiente:
informacin con respecto a las consecuencias
tanto positivas como negativas de un estudio Interpretacin de historiales mdicos y
gentico molecular. El consentimiento infor- familiares para evaluar la probabilidad
mado se debe considerar como un proceso, de que se produzca o se vuelva a producir
mediante un dilogo, no simplemente como un una enfermedad.
acuerdo contractual y debe buscar la informa-
cin y la comprensin del paciente. La natu- Informacin sobre herencia, estudios,
raleza y la duracin del proceso pueden variar gestin, prevencin, recursos e investigacin.
dependiendo del paciente, de su edad y de su
capacidad para dar consentimiento y de la Asesoramiento para fomentar las
naturaleza del estudio gentico molecular. El elecciones informadas y la adaptacin
proceso que conduce a un consentimiento al riesgo o enfermedad7.
informado debe seguir una normativa estable-
cida o unas directrices profesionales. Para 19. La naturaleza y la duracin del aseso-
algunos estudios, en concreto para los estu- ramiento o consejo depender del tipo de estu-
dios predictivos o previos a los sntomas, dio gentico, de su contexto y de sus posibles
puede ser una declaracin por escrito en la resultados. El asesoramiento gentico propor-
que se describan los riesgos y los beneficios y ciona a los individuos y a las familias con un
las limitaciones del estudio gentico para que desorden hereditario informacin precisa,
el paciente la lea y la firme antes de la evalu- completa e imparcial y ofrece apoyo en el
acin y/o de la realizacin del estudio. La doc- proceso de toma de decisiones. Puede ser un
umentacin de las pruebas de un proceso de proceso complejo, que pretende ayudar a las
consentimiento informado se debe conservar familias a sobrellevar el diagnstico de un
en el historial del paciente. Tambin se deben desorden hereditario, a afrontar sus implica-
incluir informaciones tales como, el tiempo ciones y a tomar decisiones en base a sus
que se almacenar la muestra, el deber de opciones mdicas y no mdicas. Es de especial
contactar de nuevo con el paciente si es nece- importancia en los estudios predictivos y
sario realizar de nuevo un estudio de las mues- previos a los sntomas. El asesoramiento
tras (por ejemplo, debido a avances relevantes garantiza que las prerrogativas del individuo
en los conocimientos y las tcnicas), los posibles incluyen la autonoma de eleccin para llevar
7
[Grupo de Trabajo de Definicin de la Sociedad Nacional de Asesores de Gentica; Resta R, Biesecker BB, Bennett
RL, Blum S, Hahn SE, Strecker MN, Williams JL. Una Nueva Definicin del Asesoramiento Gentico: Informe del
Grupo de Trabajo de la Sociedad Nacional de Asesores Genticos. J Genet Couns. 2006;15(2):77-83.]
30 Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007
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8
La Mejor Prctica se basa en ISO 15189, 5.6.2, que requiere que El laboratorio determinar la incertidumbre de
los resultados, siempre que sea pertinente y posible.
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incluir una evaluacin de la competencia en frente a normas externas por una auditoria
los servicios proporcionados, incluyendo la independiente. (B.4)
competencia tcnica, el nivel de estudios y
la formacin pertinente del especialista y 27. La implementacin de normativas y de
tambin el cumplimiento de las normas rele- incentivos apropiados pueden actuar como
vantes profesionales, legales y de gestin de importantes impulsores para fomentar la
calidad. (B.2) calidad de los estudios genticos moleculares.
Las Directrices reconocen como fundamental
25. Cuando la acreditacin o el reconoci- que para conseguir el objetivo de obtener y
miento equivalente se basa en las mismas nor- mantener el cumplimiento de las normas de
mas o en normas comparables, como ISO acreditacin o de reconocimiento equivalente,
15189 e ISO/IEC 17025, existe la posibilidad se requieren recursos. Tambin reconocen que
de obtener niveles similares de competencia a son necesarios para fomentar la mejora de la
nivel internacional. El acuerdo de reconoci- actuacin de los laboratorios, el estableci-
miento mutuo (MRA), contemplado por la Co- miento de acuerdos formales para la evaluacin
operacin de Acreditacin de Laboratorio y comparacin de procesos y estructuras. (B.5; B.6)
Internacional (ILAC), proporciona un funda-
mento para la equivalencia de los servicios de 28. Pueden ser necesarios (B.6; B.7) el control
laboratorio y es una base para la reciprocidad peridico y las acciones especficas para
de la acreditacin de laboratorios entre pases. garantizar que se cumplen las normas y que
Es esencial para conservar la confianza del se mantienen las mejoras de actuacin. Los
pblico en los estudios genticos moleculares, principios fomentan la diseminacin activa
que las normas de garanta de la calidad de los de los estndares de calidad a travs de la
estudios genticos sean internacionalmente formacin y acciones de acompaamiento.
comparables. (B.3)
29. Para la mayora de los estudios genticos
26. El tipo de instrumento aplicado depen- moleculares utilizados actualmente no existen
der de la naturaleza y del alcance de la materiales de referencia disponibles. El objetivo
supervisin. La supervisin reglamentaria y/o de los Principios es fomentar la colaboracin
profesional puede ser eficaz. La intervencin internacional y el establecimiento de mecanis-
se debe llevar a cabo cuando sea necesario y mos o programas9 apropiados para la recopi-
debe ser apropiada al riesgo de un resultado lacin, el desarrollo, la verificacin y el uso de
errneo de un estudio gentico. La intencin, materiales de referencia. Para lograr esto,
el significado y el proceso mediante el cual se tambin es necesario facilitar el flujo trans-
desarrollan y administran las normativas fronterizo de muestras de diagnstico cuando
deben ser transparentes. Los reguladores sea necesario para un diagnstico preciso o
deben poder justificar sus decisiones y como materiales de control de calidad, tal y
proporcionar normativas que sean prcticas como se estipula en el Principio (A.7; B.8)
y tiles para ser implementadas. Por ejemplo,
la autorizacin o licencia para un laboratorio 30. La colaboracin internacional es especial-
de estudios genticos moleculares no con- mente importante para determinados estu-
tribuye directamente a la calidad de su dios, incluyendo los de las enfermedades
resultado. No obstante, puede ser una her- de baja prevalencia y los nuevos estudios,
ramienta valiosa que es utilizada por las au- para establecer la validez analtica y clnica.
toridades para controlar a los proveedores de (B.9; B.vii)
servicios. Puede indicar un requisito espec-
fico de supervisin, especialmente cuando 31. Los laboratorios de investigacin desem-
se ofrecen estudios altamente predictivos, pean un importante papel en el desarrollo y
tales como el diagnstico prenatal. Por el la validacin de nuevos estudios especialmente
contrario, la acreditacin es una herramienta en la realizacin de estudios genticos para
potente para mejorar la garanta de la calidad. enfermedades raras. La caracterizacin de
Requiere que el laboratorio sea evaluado mutaciones en enfermedades de baja prevalencia
9
Por ejemplo: el Programa de Materiales de los Centros Estadounidenses para el Control de Enfermedades y el de
Garanta de la calidad de los Estudios Genticos de Prevencin (GTQC), EUROGentest.
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10
Algunas limitaciones importantes de los estudios genticos moleculares son 1) que puede que no detecten todas
las mutaciones asociadas con un desorden; y 2) que la presentacin clnica no siempre se puede predecir a partir
de las variantes detectadas. Un nico gen puede tener muchas mutaciones diferentes y stas se pueden producir
en cualquier parte del gen. Asimismo, la frecuencia de mutaciones comunes puede variar entre los grupos de
poblacin. El conocimiento de la tasa de deteccin para la subpoblacin del paciente es a menudo crucial para
definir su riesgo residual en el caso de un resultado del estudio negativo.
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especficos para determinados genes significa alternativos. Los mtodos alternativos incluyen
que no se puede realizar un programa de los intercambios de muestras ciegas y la re-
controles de competencia para cada estudio visin de resultados entre laboratorios, los
gentico. Asimismo, teniendo en cuenta la estudios de repeticin ciegos, los estudios
gran variedad de las metodologas y de los mediante mtodos diferentes independientes y
planteamientos de diagnstico, la disponibil- la correlacin de resultados con parmetros
idad general de los controles de competencia clnicos y de laboratorio. Si resulta aplicable,
sigue suponiendo mucho esfuerzo. los intercambios de muestras ciegas entre
laboratorios es el planteamiento preferido.
38. Las Directrices recomiendan el uso de un Estos mtodos alternativos tambin podran
proceso de revisin externo y recomiendan incluir programas genricos diseados para
que las organizaciones que realizan programas estudiar la actuacin del laboratorio en
de controles de competencia deben ser compe- etapas individuales del proceso analtico (por
tentes para hacerlo, tal y como se establezca, ejemplo, la secuencia de ADN). (C.5; C.v)
mediante una acreditacin o reconocimiento
equivalente. Esta recomendacin se basa en 40. Las Directrices reconocen como un principio,
los requisitos contenidos en las directrices de que se necesitan sistemas para supervisar y
la Cooperacin Internacional de Acreditacin resolver la mala actuacin en los controles de
de Laboratorio (ILAC) para los Requisitos para competencia. En el contexto de estas Directrices,
la Competencia de los Proveedores de Con- el trmino sistemas para supervisar los
troles de competencia (ILAC-G13:2000) y en la controles de competencia se refiere a los
Gua ISO/IEC 43-1:1996 11. Esta Gua ISO procesos y a las tcnicas estadsticas necesarias
proporciona recomendaciones para el desarrollo para establecer de forma adecuada si cada
y la realizacin de programas de controles de laboratorio participante ha cumplido o no los
competencia y proporciona una base para el niveles de actuacin satisfactorios. Por ejemplo,
reconocimiento de las equivalencias de los los controles de competencia pueden, por su
programas de Controles de competencia entre diseo, incluir tcnicas estadsticas para
las distintas jurisdicciones. (C.3; C.4) controlar la actuacin de un participante.
Estas estadsticas se pueden utilizar para
39. Muchas enfermedades genticas son poco determinar la variabilidad de la actuacin de
comunes y los estudios pueden ser realizados un participante, identificar las tendencias
nicamente por uno o unos pocos laboratorios generales y detectar las inconsistencias. Deben
del mundo que estn estudiando los genes existir procedimientos para proporcionar a los
causantes, han reclutado familias afectadas y laboratorios la reaccin apropiada. (C.6)
han desarrollado estudios propios. Esto hace
que el desarrollo de programas de controles de 41. Las Directrices reconocen que para establecer
competencia para estos servicios de enfer- niveles de actuacin aceptables, es necesaria
medades no sean posibles ya que se basan en la colaboracin entre los proveedores de
la posibilidad de comparar las prcticas, en la controles de competencia y los organismos
participacin de un nmero mnimo de centros profesionales. (C.i)
para el intercambio de muestras inter-labora-
torios y en un volumen crtico de estudios. Los 42. Para garantizar que se cumplen los
Principios reconocen estos problemas e incluyen estndares y tratar de forma efectiva la mala
estipulaciones para los estudios de enfer- actuacin persistente, es necesario un control
medades para las que no existen controles de peridico y la documentacin de medidas
competencia, al recomendar en el Principio correctivas. Los organismos reglamentarios y
C.5 que se debe contar con mtodos alterna- profesionales deben tener en cuenta qu orga-
tivos para medir la actuacin de los laborato- nismo tendr la autoridad para intervenir en
rios 12 . Las Buenas Prcticas instan a los caso de que las normas no se cumplan y cules
laboratorios a que hagan uso de estos mtodos sern estas intervenciones. (C.ii)
11
ISO/CASCO 322: ISO/IEC Gua 43: Controles de competencia mediante comparaciones interlaboratorio Parte 1:
Desarrollo y realizacin de los programas de controles de competencia 1996.
12
El principio se basa en el documento de CSLI GP29-A: Validacin de los estudios de laboratorio cuando los
controles de competencia no estn disponibles.
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Glosario
Las siguientes definiciones se proporcionan para facilitar Controles de competencia o de calidad son los procesos
la referencia. Se han redactado a partir de definiciones formales por medio de los cuales los laboratorios miden
utilizadas comnmente en documentos internacionales su actuacin frente al de sus homlogos utilizando ma-
y no representan ningn esfuerzo por parte de la OECD teriales validados externamente. [ISO/IEC 17000:2004]
para llegar a un acuerdo sobre la interpretacin de estas
definiciones ni para desarrollar nuevas. El material de Garanta de la calidad significa todas las actividades plan-
referencia de origen se incluye entre corchetes despus ificadas y sistemticas implementadas dentro de un
de la definicin. sistema de calidad y que se han demostrado como nece-
sarias para proporcionar la confianza adecuada de que
Acreditacin es un procedimiento por medio del cual un una entidad cumplir los requisitos de calidad. [ISO
organismo oficial reconoce formalmente que un organ- 9000:2000]
ismo es competente para realizar tareas especficas.
[ISO/IEC 17000:2004] Laboratorio de referencia, laboratorio externo al que se
enva una muestra para un proceso de examen comple-
Auditora es el proceso sistemtico, independiente y mentario o confirmatorio y para la realizacin de un
documentado, para obtener pruebas y evaluarlas de informe. [ISO/WD 15189 v1.05]
forma objetiva para determinar de forma objetiva la
medida en la que se cumplen los criterios de la auditora. Material de Referencia, el material, suficientemente
[ISO 9000:2000 Sistemas de Gestin de la Calidad homogneo y estable con respecto a una o ms
Aspectos Fundamentales y Vocabulario] propiedades especficas, que se ha establecido como ade-
cuado para su uso pretendido en un proceso de medicin.
Competencia es el resultado de la educacin acadmica [Gua ISO 35:2006]
bsica, de postgrado y continua, as como de la forma-
cin y la experiencia de varios aos en un laboratorio Nota 1: Material de Referencia es un trmino genrico.
mdico. [ISO 15189; 2003] Nota 2: Las propiedades pueden ser cuantitativas o
cualitativas, por ejemplo la identidad de sustancias o de
Consentimiento informado es un proceso mediante el especies.
cual un sujeto de forma voluntaria confirma su deseo de Nota 3: Los usos pueden incluir la calibracin de un
que se realice un determinado acto de estudio, despus sistema de medida, la evaluacin de un procedimiento
de haber sido informado de todos los aspectos del acto de medicin, la asignacin de valores a otros materiales
relevantes para la decisin del sujeto de participar en el y el control de calidad.
acto. El consentimiento informado es un proceso, a Nota 4: Un Material de Referencia tan slo se puede
travs de un dilogo, no simplemente un acuerdo utilizar para un nico propsito en una medida deter-
contractual, que debe buscar la informacin y la com- minada.
prensin del paciente y debe seguir normativas o direc-
trices profesionales establecidas. [Basado en Las Asesor Tcnico es un asesor que dirige la evaluacin de
Directrices de Buena Prctica Clnica ICH E6] la competencia tcnica del laboratorio o del organismo de
inspeccin para reas especficas del alcance deseado de
Director de laboratorio es la persona competente respon- la acreditacin. [ILAC G11:07/2006 Directrices de ILAC
sable de y con autoridad sobre un laboratorio. [ISO sobre Cualificacin y Competencia de los Asesores y los
15189; 2003] Expertos Tcnicos.]
Pruebas objetivas datos que respaldan la existencia de Validacin es la confirmacin mediante el examen y la
algo o para verificar algo. Las pruebas objetivas se obtencin de pruebas objetivas, de que se han cumplido
pueden obtener a travs de la observacin, procesos de los requisitos para un uso especfico pretendido. [ISO
medir, la realizacin de estudios, o por otros medios. [ISO 8402;1994 Gestin de la Calidad y Garanta de la
9000:2000] Calidad Vocabulario (Glosario)]
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Index
OECD GUIDELINES FOR QUALITY ASSURANCE IN MOLECULAR GENETIC TEST-
ING
Table of Contents
Pg.
B a c k g r o u n d ................................................................................................................... 41
P r e f a c e ........................................................................................................................... 43
1. Scope ......................................................................................................................... 47
2. Principles and best practices ..................................................................................... 48
A. General principles and best practices for molecular genetic testing ................... 48
B. Quality assurance systems in molecular genetic testing ..................................... 48
C. Proficiency testing: monitoring the quality of laboratory performance ............... 49
D. Quality of result reporting ................................................................................. 50
E. Education and training standards for laboratory personnel ............................... 51
Introduction .............................................................................................................. 55
General Terminology ................................................................................................. 56
1. General principles and practices for molecular genetic testing ........................... 57
2. Quality assurance systems in molecular genetic testing ..................................... 59
3. Proficiency testing: monitoring the quality of laboratory performance ............... 61
4. Ensuring quality in molecular genetic test result reporting ............................... 62
5. Education and training standards for laboratory personnel ............................... 63
G l o s s a r y ......................................................................................................................... 64
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Background
Since the 1980s, the use of genetic testing as countries to reduce the risk of harm from
an aid in diagnosing disease and to predict inappropriate and inaccurate testing and to
future disease risk has grown steadily. Genetic assure the quality of molecular genetic testing
testing is also just beginning to be used to procedures. Some countries have well estab-
inform prescribing of drug therapy based on lished licensing, accreditation and certification
individual genetic variation (pharmacogenetics). procedures to provide regulation and oversight
In 2006, testing is offered internationally, and to promote the quality of laboratories
through both public and private sector genetic involved in medical testing.
testing services, and there is evidence that
human samples and related data are being However, these regulatory and oversight
exchanged across borders in an environment procedures have not penetrated diagnostic
where regulatory and oversight procedures molecular genetic testing laboratories across
vary significantly between jurisdictions. This OECD Member countries to a high degree and
expanded use and internationalisation of with any consistency. One reason for this
genetic testing raises novel issues and is could be that regulations with which labora-
challenging the current regulatory frame- tories must comply are not specifically desig-
works governing genetic services1. ned for molecular genetic testing. Considerable
differences exist in the use of licensing, certi-
In 2002, OECDs Working Party on Biotechnology fication, and accreditation procedures and this
decided to carry out a survey to document the poses a number of challenges for molecular ge-
availability and extent of molecular genetic netic testing, particularly with respect to the
testing throughout the OECD Member coun- standards under which tests are performed
tries. It also documented existing quality and results are reported for clinical application,
assurance practices in use in molecular genetic and the training and qualifications required by
testing laboratories and policies for the laboratory personnel.
handling of samples and genetic data includ-
ing transfers across borders. Eighteen OECD Consequently, there is uncertainty about
member countries (Austria, Belgium, Canada, terminology and the choice of the most appro-
the Czech Republic, Finland, France, Ger- priate quality system. There is also a lack of
many, Ireland, Italy, Japan, Norway, Portugal, understanding amongst the international
Spain, Sweden, Switzerland, Turkey, the United community on the mutual acceptability of
Kingdom and the United States) participated quality assurance systems. As laboratories
in this survey. The results of the survey were increasingly provide their services to both
published as Quality Assurance and Profi- national and international customers there is
ciency Testing for Molecular Genetic Testing: a need to develop international consensus and
Summary Report of a Survey of 18 OECD best practice to assure consistency in the
Member Countries, OECD (2005). quality of services available.
The survey confirmed the steady growth of The need to take international action to
molecular genetic testing and its widespread resolve the issues was endorsed by OECDs
availability. The survey also showed that labo- Committee for Scientific and Technological
ratories in all countries use both formal and Policy meeting at ministerial level in January
informal professional referral networks that 2004 as well as by OECD health ministers at
exist either within or outside each country to their meeting in May 2004. OECD Member
send samples across borders. A number of countries thus agreed to develop guidelines
mechanisms are in place in all OECD Member setting out principles and best practices for
1
Genetic Testing: Policy Issues for the New Millennium, (2000) OECD.
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quality assurance in molecular genetic testing Principles are policy recommendations speci-
for clinical purposes in consultation with fically directed to Governments and those
experts and interested parties. This work led involved in the regulation of genetic services.
to the Recommendation on Quality Assurance Best Practices are recommendations that aim
in Molecular Genetic Testing adopted by the to provide operational guidance in implementing
OECD Council on 10 May 2007 which sets out, the Principles and are directed to professional
inter alia, a number of principles and best bodies and providers of molecular genetic testing
practices relevant to this field of activity. The services in developed and developing economies.
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Preface
Genetic tests may be highly predictive of the Principles are directed primarily at govern-
future health of the individual. They are relevant ments and those involved in the regulation of
to healthy people as well as those showing symp- genetic services, whereas Best Practices
toms of a condition and may have important im- primarily are aimed at professional associa-
plications for the relatives of the person tions and directors of molecular genetic
tested. The single laboratory test to establish testing laboratories and others involved in the
a genotype is usually not repeated and its provision of molecular genetic testing. The
result forms a permanent part of the medical ethical and legal principles set out in interna-
record. Consequently, it is important that tional declarations and agreements and the
services are provided with the appropriate diversity of systems and jurisdictions within
level of support to the patient and their family and between countries have been recognised
prior to the offer of a genetic test and following during the development of these Guidelines.
the result. Whilst good laboratory practices
and adherence to quality standards are the re- These Guidelines focus on certain aspects of
sponsibility of all medical testing laborato- the provision of genetic services. They concern
ries, these features of molecular genetic molecular genetic testing offered in a clinical
testing place an enhanced duty on laboratories context, and the quality assurance practices of
to assure the quality of their services. Research laboratories that carry out such tests. They do
laboratories play a valuable role in the devel- not address testing carried out only for research
opment and validation of new tests particu- purposes.
larly in the provision of genetic testing for
rare diseases. Governments, regulators and The Guidelines address genetic testing for
professional bodies have a responsibility to variations in germ line DNA sequences or
ensure that all genetic testing services are products arising directly from changes in her-
offered within a quality assurance framework itable genomic sequences that predict effects
that retains the confidence of the public. on the health, or influence the health manage-
ment, of an individual. They focus on molecu-
These Guidelines comprise Principles and Best lar genetic testing for the diagnosis of a
Practices for quality assurance in molecular particular disease or condition and predictive
genetic testing for clinical purposes. The Guide- genetic testing often carried out before any
lines seek to assist both OECD and non-OECD clinical signs of the disease or condition
Member countries in the development and appear. They are relevant to tests for heritable
introduction of appropriate quality assurance DNA variants that predict the response profile
procedures to: of an individual to a drug or course of therapy
and that affect susceptibility to disease,
Promote minimum standards internationally patient prognosis, counselling, treatment and
for quality assurance systems and mole- family planning.
cular genetic testing laboratory practices.
Facilitate mutual recognition of quality Molecular genetic tests require particular
assurance frameworks. consideration since these tests may be performed
Strengthen international co-operation on asymptomatic individuals and results may
and facilitate, where appropriate, the have relevance to important lifetime decisions
cross border flow of samples for clinical both for the individuals being tested and for
purposes in accordance with recognised their family and children. The Guidelines
principles for their handling, storage, reflect this particular responsibility of molec-
safety privacy and confidentiality. ular genetic testing and place emphasis on the
Increase public confidence in the gover- accuracy of all aspects of the testing and re-
nance of molecular genetic testing. porting process including forming links to
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appropriate levels of counselling. In part, these Part One of this publication sets out the Council
Guidelines are also relevant and applicable to Recommendation on Quality Assurance in
aspects of clinical cytogenetics testing and Molecular Genetic Testing which provides
biochemical genetic testing. They are not Principles applicable to quality assurance in
designed to address directly the areas of molecular genetic testing together with related
testing for somatic mutations, variants Best Practices. The Principles provide a
important in tissue matching, genetic analysis framework within which to conceive measures
of pathogenic organisms and identity testing, that assure all aspects of quality, including
though all share related technologies. competence to carry out and report molecular
These Guidelines are intended to be evolution- genetic tests as well as the education and training
ary in nature and will therefore need to be re- of laboratory personnel. The Best Practices are
viewed within four years of adoption and practical means for putting into place that
thereafter periodically in light of new genetic framework. Part Two of the Guidelines
knowledge, technological advances, evolution contains explanatory Annotations which elabo-
of quality management and societal needs and rate on the Principles and Best Practices in Part
to ensure that they are achieving the desired One. Finally, a Glossary of terms as well as a list
objectives. of other relevant publications is provided.
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Part I.
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1. Scope
This Recommendation applies to quality as- and predictive genetic testing often carried
surance of molecular genetic testing offered in out before any clinical signs of the disease
a clinical context. It addresses genetic testing or condition appear. It is relevant to tests
for variations in germ line DNA sequences or for heritable DNA variants that predict the
products arising directly from changes in response profile of an individual to a drug or
heritable genomic sequences that predict course of therapy and that affect susceptibil-
effects on the health, or influence the health ity to disease, patient prognosis, counselling,
management, of an individual. treatment and family planning. It does not
It focuses on molecular genetic testing for the address testing carried out only for research
diagnosis of a particular disease or condition purposes.
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B.4 The requirements adopted by legal, regu- B.v Laboratories should have policies and
latory and professional bodies for laboratories procedures to regularly evaluate internal qual-
to be recognised as competent through an ity control measures and to document
accreditation or equivalent recognition should findings and any corrective actions taken to
be accessible, clearly stated, and effective. address deficiencies.
B.5 Regulation and incentives should be B.vi Laboratories should make available to
introduced to facilitate the development and service users current evidence concerning the
implementation of accreditation or other clinical validity and utility of the tests they offer.
equivalent recognition.
B.vii Developers, manufacturers, health care
B.6 Impediments to achieving the require- professionals and laboratories, as well as other
ments for accreditation or other equivalent relevant groups, should collaborate to estab-
recognition should be identified and addressed. lish the clinical validity and utility of tests,
particularly for rare conditions.
B.7 Governments and/or regulatory bodies
should ensure that systems are in place to B.viii Laboratories should cooperate with relevant
monitor and address instances where laborato- national and international institutions to
ries do not meet quality assurance requirements. collect, develop, verify and make available
reference materials for molecular genetic tests.
B.8 Governments should encourage interna-
tional collaboration for the development, ver- B.ix Laboratories should use available refer-
ification, availability and use of reference ence materials and/or family-specific (private)
materials for molecular genetic testing. mutation controls where appropriate and available.
B.ii Internationally accepted standard termi- C.3 Providers of proficiency testing schemes
nology and nomenclature should be adopted should be competent to provide such schemes,
and used consistently with respect to quality as established by accreditation or equivalent
assurance systems. recognition.
B.iii Technical assessors acting on behalf of accred- C.4 Accreditation or equivalent recognition
itation bodies or bodies delivering equivalent should be the basis for the international recogni-
recognition should have qualifications, training tion of proficiency testing scheme providers.
and experience relevant to molecular genetic testing.
C.5 Governments, regulatory and profes-
B.iv Laboratories should have policies and sional bodies should take steps to encourage
procedures to document the analytical valid- laboratories to participate in accredited profi-
ity of all tests performed. ciency testing schemes or, when not available,
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to use alternative methods to assess the qual- ten and/or electronic report to the referring cli-
ity of the tests they perform. nician or health professional.
C.6 Systems to monitor laboratory perform- D.2 Within jurisdictions where reports may
ance, and address persistent poor perform- be issued directly to patients, governments,
ance, should be in place. regulatory and professional bodies should
encourage all laboratories performing clinical
molecular genetic tests to recommend that
Best Practices patients consult an appropriate clinician or
health care professional to help them understand
C.i Proficiency testing providers and profes- the implications of the test result.
sional bodies should collaborate to establish
acceptable performance levels for laboratories D.3 Governments and regulators should
offering molecular genetic tests. require that in issuing and archiving reports,
all laboratories comply with applicable law and
C.ii Regulatory and professional bodies respon- regulations, including those concerning the
sible for monitoring laboratory performance confidentiality of information.
against agreed standards should identify persist-
ent poor performance and ensure that timely cor- D.4 The interpretation of molecular genetic
rective actions are taken and documented. test results should be appropriate to the indi-
vidual patient and clinical situation and
C.iii Proficiency testing schemes should be should be based on objective evidence.
structured to assess all phases of the labora-
tory process, including result reporting.
Best Practices
C.iv Providers of proficiency testing should develop
and modify proficiency testing schemes to take D.i Reports should communicate information
into account the evolution of analytical methods. effectively taking into account that the
recipient may not be a specialist health care
C.v Laboratories should participate in a professional.
proficiency testing scheme for every disease
for which they test, where such schemes are D.ii Reports should be timely, accurate,
available. When not available, they should concise, comprehensive, and communicate all
participate in alternative methods relevant to essential information to enable effective
the tests they perform. decision-making by patients and health care
professionals.
C.vi Laboratories should make the fact that they
participate in proficiency testing publicly known. D.iii Reports should use applicable interna-
tionally accepted terminology and nomenclature
C.vii Individual laboratory performance in profi- including identification of reference sequences.
ciency testing schemes may be disclosed on a
voluntary basis by the laboratory concerned but D.iv Laboratories should inform service users
should not be made public by proficiency testing of the patient and family information the
scheme providers unless so required by law. laboratory requires to ensure the appropriateness
of the test request and to interpret the results.
D.1 All laboratories should issue molecular 1 Identification that unequivocally links
genetic testing results in the form of a writ- the report to the patient.
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12 The date of issue of the report. E.6 Where governments, regulators and
professional bodies recognise medical and sci-
D.vii Where appropriate, the test report should entific qualifications awarded by foreign insti-
also include the following information: tutions, such recognition should be
extended, as appropriate, to equivalent quali-
1 A recommendation for genetic coun- fications in molecular genetic testing.
selling by a qualified health care
professional. E.7 All personnel involved in molecular ge-
netic testing should practice within the frame-
2 Implications for other family members. work formed by applicable legal, ethical and
professional standards.
3 Recommendations for follow up
testing.
Best Practices
D.viii All the essential and relevant elements of
test results and interpretation reported by a E.i Measures to assure professional compe-
referral laboratory should be included in the tence should be established. These measures
report to the health care professional who should be comparable to those applied in other
ordered the test. areas of laboratory medicine. They should
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include systems to validate requirements for for the purpose of reporting a diagnostic re-
education, training, qualifications and skills sult on any patient material.?
specific to molecular genetic testing.?
E.iv Education and training in genetics
E.ii Appropriate specialist qualifications, ed- should be recognised by regulatory and/or
ucation and training standards for individuals professional bodies as an essential element to
directing molecular genetics laboratories strengthen professional competence to deliver
should be established. The minimum qualifi- molecular genetic testing.
cation required to direct a laboratory should
be an MD or PhD or a recognised equivalent E.v Laboratory directors should ensure that
qualification. Educational requirements should all personnel involved in molecular genetic
include formal training in molecular genetics testing participate in continuing education
and where available, certification in the and training programmes appropriate to their
specialty of clinical laboratory molecular roles and designed to further develop and
genetics, or another relevant discipline. maintain competence.
E.iii Laboratory directors should ensure that E.vi Comparison of specialist education and
all laboratory personnel have relevant train- training systems between jurisdictions
ing and have their competence documented should be facilitated as a means to establish
prior to performing molecular genetic testing equivalence.
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Part II.
Annotatios
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Introduction
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General Terminology
5. The Guidelines apply to molecular genetic systems. The ISO 15189 standard is relevant
tests offered in a clinical context. to all general medical laboratories but not
specific to molecular genetic testing laborato-
6. For the purpose of these Guidelines, ries. The related ISO 17025 standard is
quality assurance means all those planned and designed for the accreditation of testing and
systematic activities implemented within a calibration laboratories of all types. These
quality system, and demonstrated as needed standards are not themselves accreditation
to provide adequate confidence that an entity systems but may be referred to by the author-
will fulfil requirements for quality2. itative bodies that award accreditation.
7. The Guidelines acknowledge that different 10. Accreditation standards related to clinical
mechanisms or procedures exist across OECD laboratories place emphasis on having an
Member countries to promote quality assur- effective quality assurance system in place; on
ance in laboratory medicine. Instruments a commitment to meeting the needs of
relevant to quality assurance may include: patients and their doctors as users of labora-
accreditation, licensing, certification, profi- tory services; and on a need for a continuous
ciency testing, internal quality control cycle of quality improvement at the centre of
measures, documentation of policies and all policy making and operational decisions.
procedures, and/or assurance of personnel
competence that may include certification or 11. Establishing the competence of a labora-
registration of laboratory personnel. tory through an accreditation procedure
includes an assessment of the laboratory
8. Accreditation is a procedure by which an infrastructures and all internal quality control
authoritative body gives formal recognition and quality assessment measures. For exam-
that a body is competent to carry out specific ple, to achieve accreditation a laboratory
tasks3. It is a public recognition of a labora- must, amongst other requirements, be ade-
torys competence. It is only granted after a quately staffed by personnel with appropriate
thorough on-site assessment by technical qualifications and training. It must maintain
assessors of the management, environment, adequate documentation, including standard
policies and procedures of the laboratory in operating procedures for analytical tests. In
addition to specific scientific/technical compe- addition it must demonstrate external assess-
tences measured against external standards. ment of its tests preferably through participa-
Accreditation is also applicable to organisa- tion in a recognised laboratory proficiency
tions providing proficiency testing. The testing scheme. It may also be obliged to
Guidelines also conceive of equivalent recogni- demonstrate satisfactory performance and
tion (see paragraph 24). In 2003, the OECD show that it is responsive to shortcomings
quality assurance survey provided evidence demonstrated through proficiency testing as
that accreditation is the most effective way to well as deviations in performance discovered
improve quality assurance, but it is not as a result of routine internal laboratory
widespread in diagnostic molecular genetic quality control measures.
testing laboratories in OECD Member countries4.
12. In contrast, licensing is a legal permit or
9. International standards are relevant to a formal permission from a constituted autho-
the design of jurisdiction specific accreditation rity or governmental agency to operate a
2
ISO 9000.
3
ISO/IEC17000:2004.
4
Quality Assurance and Proficiency Testing for Molecular Genetic Testing: Summary Report of a Survey of 18
OECD Member Countries, OECD (2005).
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laboratory. It may involve documenting the ex- the genotype results in the context of the
istence, institutional accountability and, in clinical scenario and to report their findings
general terms, the activities of the facility, for in their usual reporting format.
example the types of service provided. In
return, the laboratory is officially registered
and may be publicly listed. Practice amongst
licensing authorities varies. The granting of a
1. General principles and
licence may or may not require a formal audit practices for molecular
of policies, procedures or practice by the
responsible authority. In some jurisdictions
genetic testing
licensing authorities require formal accredita-
tion (see paragraph 8).
15. Molecular genetic testing within the
13. Certification is a procedure by which a scope of these Guidelines may have important
third party gives written assurance that a consequences for the health and well-being of
product, process or service conforms to specific an individual and their relatives. Therefore,
requirements5. Certification is a well-recognised support to the individuals concerned, appro-
indicator of the quality management of an priate to the potential outcomes of testing is
organisation but it is less stringent than important. The test may be used to support a
accreditation. It involves a procedure by which diagnosis, or may be used to predict, with
a third party gives written assurance that a variable certainty, later onset of disease. In
product, process or service conforms to specific jurisdictions where permitted, genetic testing
requirements but does not require examina- may be carried out to determine carrier status
tion of specific competences against external or for pre-implantation or prenatal testing. (A.2)
standards. ISO9001:2000 is an example of a
certification standard that can be applied to 16. The Principles specify that all genetic
any manufacturing process or service. In testing services should be subject to a quality
contrast, a certification programme for persons assurance framework. In this context, a frame-
that is accredited to ISO/IEC 17024 requires work is considered to be the totality of the
examination of the competence of persons. mechanisms that directly or indirectly affect
the quality of a laboratory service. These may
14. Proficiency testing schemes are systems include statutory, non statutory, regulatory
to determine laboratory performance for and/or professional mechanisms such as code
particular fields of testing 6. They allow a of practices and clinical guidelines. (A.3)
laboratory to compare its performance for an
individual test or technique against that of 17. A process leading to informed consent is a
other laboratories. Typically, a proficiency necessary step for medical procedures including
testing scheme provides a number of biolog- molecular genetic testing and the responsi-
ical samples of known and validated bility of health care professionals. Exceptions
genotype to participating laboratories. Labo- are recognised in regulation, law, and profes-
ratories are asked to genotype the samples sional guidelines. Within these Guidelines
and return their reports to the proficiency informed consent is intended as a safeguard
testing scheme organiser. Genotype accuracy to ensure the patients autonomy and to
is assessed by a panel of experts and indi- provide an opportunity to learn and understand
vidual comments on performance are returned information with respect to both the positive
to participating laboratories. Laboratories are and negative consequences of a molecular
asked to act on shortcomings to improve their genetic test. Informed consent should be
performance. Proficiency testing schemes may considered as a process, following a dialogue,
also assess the reporting practices of the not simply a contractual agreement and
participating laboratories, by providing mock should strive for patient education and
clinical scenarios with the proficiency testing understanding. The nature and duration of the
samples and asking participants to interpret process may vary depending on the patient,
5
ISO/IEC17000:2004.
6
Based on UKAS Accreditation of Providers of Proficiency Testing Schemes for Laboratory Testing. 2005.
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his/her age and ability to consent, and the test, its context and its potential outcomes.
nature of the molecular genetic test. The Genetic counselling provides individuals and
process leading to informed consent should families with a heritable disorder with accu-
follow established regulation or professional rate, full and unbiased information and offers
guidelines. For some tests, in particular for support in the decision making process. It
predictive or pre-symptomatic testing, it may may be a complex process, which seeks to help
take the form of a written statement describ- families to cope with the diagnosis of a herita-
ing the risks and benefits and limitations of ge- ble disorder, to face its implications and to
netic testing for the patient to read and sign make decisions on the basis of their medical
before the evaluation and/or test is performed. and non-medical options. It is of particular
Documenting evidence of an informed consent relevance in predictive and pre-symptomatic
process should be preserved in the patient testing. Counselling ensures that the individ-
record. Information such as length of time the uals prerogatives include autonomy of choice
sample will be stored, duty to re-contact if to undertake or not to undertake the test, free-
samples might be retested (e.g. due to relevant dom from third party pressures, and that con-
advances in knowledge and technologies), fidentiality is respected. (A.5)
possible secondary use(s), potential third-party
access to samples, procedures to protect confi- 20. Thousands of molecular genetic tests are
dentiality (coding/de-identification), may also available to patients at risk of heritable single
be included. Relevant international recommen- gene conditions. Most of these conditions are
dations and declarations on informed very rare. Given the large number of genetic
consent include the (1997 UNESCO) Universal disorders, and the need to design and validate a
Declaration on the Human Genome and specific set of diagnostic assays for each, no
Human Rights; the (2003 UNESCO) Interna- single country can be self-sufficient in the
tional Declaration on Human Genetic Data; provision of molecular genetic testing. This
and the (2005 UNESCO) Universal Declaration results in exchange of patient material and
on Bioethics and Human Rights (A.4) genetic testing across national borders. In 2003,
the OECD quality assurance survey reported that
18. Together with the offer of a genetic test, at least 18,000 samples crossed 18 OECD Mem-
consideration must be given by a health care ber countries borders. Transborder flow is
professional to the need for pre-and post-test clearly a mechanism to fill a significant gap in
genetic counselling. For the purpose of these the availability of tests for rare disorders in many
Guidelines, genetic counselling is the process countries. The Principles recognise the need to
of helping people understand and adapt to the enable and facilitate this exchange through
medical, psychological and familial implica- clearly stated, transparent, internationally
tions of genetic contributions to disease. This agreed standards and procedures. (A.7)
process integrates the following:
21. Molecular genetic testing involves the
Interpretation of family and medical processing and exchange sometimes across
histories to assess the chance of borders of diagnostic tissue samples and
disease occurrence or recurrence. clinical details. These are personal data that
may be considered sensitive. Such exchange
? Education about inheritance, testing, should be facilitated, as appropriate, except
management, prevention, resources where the OECD privacy guidelines are not
and research. substantially observed, including their secu-
rity safeguards principle. The OECD Guide-
? Counselling to promote informed lines on the Protection of Privacy and
choices and adaptation to the risk or Transborder Data Flows and Guidelines for
condition7. the Security of Information Systems and
Networks provide minimum standards for the
19. The nature and duration of counselling protection of personal data and the security of
should be dependent on the type of genetic the systems and networks used for their
7
[National Society of Genetic Counselors Definition Task Force; Resta R, Biesecker BB, Bennett RL, Blum S, Hahn
SE, Strecker MN, Williams JL. A New Definition of Genetic Counselling: National Society of Genetic Counselors
Task Force Report. J Genet Couns. 2006;15(2):77-83.]
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8
The Best Practice is based on ISO 15189, 5.6.2, which requires that The laboratory shall determine the uncertainty
of results, where relevant and possible.
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to achieve this objective. They also recognise which are to be used for health care are veri-
that establishment of formal arrangements for fied and reported within an acceptable quality
evaluation and benchmarking of processes, assurance framework. (B.i)
and structures to encourage performance
improvement are necessary. (B.5; B.6) 32. The OECD 2003 survey of quality assur-
ance molecular genetic testing laboratory
28. Principles encourage active dissemination practice revealed a lack of clarity and consis-
of quality standards through training and tency in the adoption and use of the existing
facilitation. Regular monitoring and specific terminology relevant to quality assurance; for
actions may be necessary to ensure that standards example, different meanings are often assigned
are being met and performance improvements to the terms accreditation, certification
are maintained. (B.6; B.7) and licensing. Governments, regulatory and
professional bodies should encourage consistent
29. For most molecular genetic tests in use use of internationally agreed terminologies and
today, there are no reference materials available. nomenclature. (B.ii)
The objective of the Principles is to encourage
international collaboration and the esta- 33. The policies and procedures to document
blishment of appropriate mechanisms or the analytical validity of tests should be suffi-
programmes9 for the collection, development, cient to satisfy external assessment. (B.iv)
verification and use of reference materials. To
achieve this, it is also necessary to facilitate 34. Information pertaining to the clinical
cross-border flow of diagnostic samples when validity and utility of a test, relevant to the
needed for precise diagnosis or as refe- patients served, should be made available to
rence/quality control materials, as stated in service users (healthcare professionals and pa-
Principle (A.7; B.8) tients). It should be based on relevant existing
medical guidelines and peer reviewed litera-
30. International collaboration is particularly ture and may include or be supplemented by
important for certain tests, including those for in-house studies appropriate for peer review.
rare diseases and new tests, in establishing Sources of data should be cited. (B.vi)
analytical and clinical validity. (B.9; B.vii)
35. Clinical validation of a genetic test
31. Research laboratories play a valuable role reflects its ability to correctly classify individ-
in the development and validation of new tests uals with respect to their disease status or
particularly in the provision of genetic testing risk. Measurements of validity include sensi-
for rare diseases. Characterization of muta- tivity, specificity, positive predictive value, and
tions in rare diseases is not always available negative predictive value10. Predictive values
in an accredited or recognized equivalent are heavily dependent on the prevalence of the
molecular genetic testing laboratory for a condition in the population being tested. As a
number of reasons, including the fact that the result a test may be clinically valid when
infrequency of such conditions makes this applied to individuals from a high risk popula-
activity resource-prohibitive for such labora- tion, but not so when applied to the general
tories. Consequently, characterization of muta- population. Thus, an assessment of who
tions in rare diseases is often only undertaken should be offered the test is part of the
by a small number of research laboratories in assessment of clinical validity. Clinical utility
the world that are studying causative genes refers to the anticipated effect(s) of the clinical
and recruiting affected families to further use of the test result, including on health
the research in this area. The Best Practice outcomes, recognising that a variety of factors
recommends that results of clinical importance influence this outcome. (B.vi; B.vii)
9
For example: The US Centers for Disease Control and Prevention Genetic Testing Quality Control Materials
Program (GTQC), EUROGentest.
10
Important limitations of molecular genetic tests are 1) that they may not detect every mutation associated with a
disorder and 2) that the clinical presentation cannot always be predicted from the variants detected. A single gene
can have many different mutations and these can occur anywhere along the gene. In addition, the frequency of
common mutations may vary among population groups. An understanding of the detection rate of the test for the
patients subpopulations is often crucial in defining their residual risk in the event of a negative test result.
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11
ISO/CASCO 322: ISO/IEC Guide 43: Proficiency Testing by inter-laboratory comparisons -Part 1: Development and
operation of proficiency testing schemes. 1996.
12
The principle is based on CSLI document GP29-A: Validation of Laboratory Tests When Proficiency Testing is not
available.
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Regulatory and professional bodies should does not always happen. Some jurisdictions
consider what body will have authority to in- permit ordering of genetic tests directly by
tervene in case standards are not being met members of the public, and such individuals
and what interventions these will be. (C.ii) may receive results without the involvement
of a health care professional. In other situa-
tions, patients may receive a copy of their
genetic test report which has also been sent to
4. Ensuring Quality in Mo- their health care professional. This Principle
seeks to ensure that all patients receiving
lecular Genetic Test Re- reports directly from a laboratory also receive
sult Reporting a recommendation to consult a health care
professional about the result and its possible
implications. (D.2)
43. For the purpose of these Guidelines, the 47. The report should be clear and complete,
test result report is the factual presentation of to ensure both understanding of the test
results of tests done in a laboratory useful for result by health-care professionals (who may
patient management and counselling. not be familiar with the technologies used)
and subsequent effective communication with
44. When genetic testing is ordered to deter- the patient. The Guidelines recommend that
mine a genotype associated with disease, when reporting the results of a molecular
predisposition to a disease, or to predict an genetic test, the laboratory should report the
individuals response to a medicine, the test result, information on the method by
genotype, in itself, can be uninformative or which it was reached and the genetic interpre-
misinterpreted if appropriate test, patient or tation of the result. Test results may have far
family-specific information is not taken into reaching consequences for the individual pa-
consideration. Genetic test results may have tient and their family particularly in the case
implications for other family members, and it of a highly penetrant disorder. (D.i; D.ii)
is important that the health-care professional
receiving the report understands these impli- 48. For historical reasons, a number of common
cations. For carrier, pre-symptomatic and suscep- mutations have names that do not conform to
tibility testing, the patient is often asymptomatic standard nomenclature schemes. To avoid
and the test result may be the sole indicator confusion, the Best Practices recommend that
of increased risk. As such, it is essential the common designation of such mutations
that the test result report communicates the continue to be used alongside standardised
certainty or uncertainty of the analytic test nomenclature. Reports should indicate which
result, its limitations and, where appropriate, system is being used. (D.iii)
the implications for the patients tested and
their family. 49. The utility of a molecular genetic test
report is often dependent on the accuracy and
45. Principles recommend that all labora-to- adequacy of information provided to the labo-
ries reporting clinical molecular genetic test ratory. The Best Practices recommend that all
results issue a written and/or electronic report essential and relevant elements necessary for
to the referring health professional. Within the laboratory to perform appropriate testing
the Guidelines, health professionals are should follow the patient specimen through
persons authorised by local and/or national the entire testing process including the transfer
bodies to use molecular genetic tests for of a specimen to a referral laboratory. (D.iv; D.viii)
patient counselling and/or management.
Health professionals may include physicians, 50. A referral laboratory is an external labo-
nurses, midwives, physician assistants, and ratory to which a sample is submitted for a
genetic counsellors. (D.1) specialist, supplementary or confirmatory
examination procedure and testing. It is
46. While it is recognised best practice that important that the integrity of the report from
genetic test results should be provided to the referral laboratory is maintained in the report
patients by a health care professional, this provided to the health care professional (D.viii)
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51. Information provided by the referring 55. Lack of specialist training programmes in
health care professional and used in the inter- molecular genetics may lead to inadequate
pretation of the genotype may include: rele- availability of competent staff with conse-
vant demographic information, clinical data quences for quality assurance. Education and
and information about a family history and training programmes may be necessary to
clinical sensitivity and specificity. The inter- meet the growing personnel requirements of
pretation should be developed to ensure that diagnostic molecular genetic testing labora-to-
the recipient of the report is able to understand ries. Jurisdictions lacking such programmes
the clinical usefulness and limitations of the are encouraged to consider the adoption or
test result. Where the quantity or quality or development of such programmes. (E.4)
the adequacy of the sample received may affect
the result, this should be noted in the report. 56. The definition of core competencies for
Identification must unequivocally link the diagnostic molecular genetic testing labora-
patient to the report. (D.vi) tory personnel at all levels may differ across
jurisdictions and even within the same
country. The Guidelines recognise that there
is a need to facilitate mutual recognition
5. Education and of equivalent qualifications and establish
mechanisms for comparison of specialist
Training Standards for education and training programmes between
laboratory personnel jurisdictions. (E.6; E.vi)
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Glossary
The following definitions are provided for ease Proficiency testing is the formal process by
of reference. They are drawn from definitions which laboratories measure their performance
commonly used in international instruments against that of their peers using externally
and do not represent an effort by OECD to validated materials. [ISO/IEC 17000:2004]
agree on interpretations of these definitions
or develop new ones. The source material Quality assurance means all those planned
reference is acknowledged in square brackets and systematic activities implemented within
following the definition. a quality system, and demonstrated as needed
to provide adequate confidence that an entity
Accreditation is a procedure by which an will fulfil requirements for quality. [ISO 9000 : 2000]
authoritative body gives formal recognition
that a body is competent to carry out specific Referral laboratory is the external laboratory
tasks. [ISO/IEC 17000:2004] to which a sample is submitted for a supple-
mentary or confirmatory examination proce-
Audit is the systematic, independent and docu- dure and report. [ISO/WD 15189 v1.05]
mented process for obtaining evidence and
evaluating it objectively to determine the Reference Material is the material, sufficiently
extent to which audit criteria are fulfilled. homogeneous and stable with respect to one
[ISO 9000:2000 Quality Management Systems- or more specified properties, which has been
Fundamentals and Vocabulary] established to be fit for its intended use in a
measurement process. [ISO Guide 35:2006]
Competence is the product of basic academic,
postgraduate and continuing education, as Note 1: Reference Material is a generic term.
well as training and experience of several y Note 2: Properties can be quantitative or quali-
ears in a medical laboratory. [ISO 15189; 2003] tative, e.g., identity of substances or species.
Note 3: Uses can include the calibration of a
Informed consent: a process by which a measurement system, assessment of a meas-
subject voluntarily confirms his or her urement procedure, assigning values to other
willingness in a particular testing act, after materials, and quality control.
having been informed of all aspects of the act Note 4: A Reference Material can only be used
that are relevant to the subjects decision to for a single purpose in a given measurement.
participate in the act .Informed consent is a
process, following a dialogue, not simply a Technical Assessor is an assessor who conducts
contractual agreement, should strive for the assessment of the technical competence of
patient education and understanding and the laboratory or inspection body for specific
should follow established regulation or area(s) of the desired scope of accreditation.
professional guidelines. [Based on ICH Good [ILAC G11:07/2006 ILAC Guidelines on Quali-
Clinical Practice Guidelines E.6] fication and Competence of Assessors and
Technical experts]
Laboratory director is the competent person
with responsibility for, and authority over a Validation is the confirmation by examination
labo-ratory. [ISO 15189; 2003] and provision of objective evidence that the re-
quirements for a specific intended use are ful-
Objective evidence is the data supporting filled. [ISO 8402;1994 Quality Management
the existence or to verify something. Objective and Quality Assurance - Vocabulary (Glossary)]
evidence may be obtained though observation,
measurement, test, or other means. [ISO 9000:2000]
64 Directrices de la OECD para la gestin de la calidad de los estudios genticos moleculares - AETS - Diciembre / 2007