Edition of 19 November 2006

The challenges of Europe’s biochemical genetic testing are currently handled by the network of excellence EuroGentest. But what of rare disease genetic testing challenges currently encountered on the other side of the “Big Pond” ?

Spotlight recently talked to Steve Groft, Director of the Office of Rare Diseases (ORD) at the US National Institute for Health (NIH), who explained the results of a key working meeting organized last month in Atlanta by the ORD/NIH, attended by major decision-makers from the North American genetic testing (GT) community on “Quality, Access, and Sustainability of Biochemical Genetic Testing”. The talks are the latest in a series of events dealing with this hot topic including a Conference in Rockville 2005 and Workshop in 2004, focussing on biochemical genetic testing as a major area of laboratory testing for genetic diseases.

Orphanet attended this otherwise exclusively North American event. Participants were welcomed by Drs. Joe Boone, CDC and Steve Groft, NIH ORD. Plenary presentations included an overview and outlook of biochemical genetic testing by Dr. Mike Watson, American College of Medical Genetics (ACMG); results of a recent Society for Inherited Metabolic Disorders (SIMD) laboratory survey by Drs. Carol Greene and Bruce Barshop; European efforts on information resources for genetic testing by Dr. Valérie Thibaudeau for Orphanet and Eurogentest; updates on the Collaboration, Education, and Test Translation (CETT) Program for Rare Genetic Diseases by Dr. Giovanna Spinella, ORD, NIH; and examples of coordination between biochemical and molecular genetic testing in improving diagnosis and patient management by Drs. David Ledbetter, Art Beaudet, and Andy Faucett. Participants then formed 3 break-out groups: Access and Sustainability, Quality Assurance, and Information Resources, to address issues more specifically in each of the focus areas.

The presentations and discussions revealed a surprising amount of common ground between European and US genetic testing policy. Europe’s experience with the recent Eurogentest project for public access, up-to-date information on genetic testing that is harmonising European standards provides an interesting parallel with the longer-established US CLIA certification model. The US regulation is firmly backing GT practice and a recent Progress Report from US Congress has addressed the development of diagnostic tests, stressing the need to meet the CLIA (Clinical Laboratory Improvement Amendments).


SPOTLIGHT Interview with Steve Groft, Office of Rare Diseases (ORD) at the US National Institute for Health (NIH)

Orphanews: What were the chief aims of the Atlanta “Quality” talks ?
SG: Our objectives can essentially be summed up in two words: Access & Availability. The US CETT Programme (Collaboration, Education & Test Translation Program)is designed to improve access to biogenetic and molecular diagnostic testing and “essential” prenatal testing, whilst the public availability of the genes programme is all-important. It is designed to improve understanding of the CLIA and testing quality standards including collection of the genotype and clinical information.

Read the full SPOTLIGHT interview…


Call for reader feedback… Do you have any ideas or questions for the US Office of Rare Diseases ?
If so, Steve Groft and his colleagues would like to hear from you.

The Orphanet Journal of Rare Diseases, in collaboration with Biomed Central, publishes free access articles on rare diseases and orphan drugs indexed by Pubmed. It has added the following 10 new articles to its online collection since the beginning of October 2006:

New online articles:

Multiple endocrine neoplasia type 2

Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40

Congenital pulmonary lymphangiectasia

Klinefelter syndrome and other sex chromosomal aneuploidies

Primary sclerosing cholangitis

Retinitis pigmentosa

Foetal and neonatal alloimmune thrombocytopaenia

Multiple endocrine neoplasia type 1

Tuberous sclerosis

The Challenges of Proteus Syndrome: diagnosis and management


Forty-five articles have been published since the Journal's creation on 1 March this year, of which 42 are Review articles, 1 is a Case study, 1 is a Research article and 1 is an Editorial. Nine of these published articles have already been given the Highly Accessed label which means in practice that each article has received at least 500 hits during the fortnight immediately following its publication.

Click here for a complete definition of the Highly Accessed label.

Submit your article now!

Severe myoclonic epilepsy in new-borns: Diacomit now set for authorisation in Europe

Following a positive opinion from EMEA, the anti-epileptic drug, Diacomit (stiripentol) should soon obtain conditional marketing authorisation for use in the treatment of severe myoclonic epilepsy in new-borns, associated with clobazam and valproate. The Biocodex laboratories, which market the medication, are committed to supplying the additional data presenting the efficacy of stiripentol associated with maximum doses of clobazam and valproate, and comparing the bio-availability of Diacomit in sachets and capsules.

The EMEA will reevaluate Diacomit each year to confirm that the benefit-risk remains positive. Diacomit is the 32nd orphan drug to obtain a positive opinion for its marketing in Europe. It has retained its positive opinion in France since 2002 for the same indication in the frame of a compassionate use cohort.

EMEA Press release; (16-18 Oct 2006)


Glivec receives indication extensions in Europe and the US but Novartis withdraws a marketing authorisation extension

Glivec (imatinib mesylate) recently received a positive opinion from the EMEA's Committee for Medicinal Products for Human Use (CHMP) following its meeting held on 16-18 October, for a marketing authorisation extension regarding:

- the treatment of myelodysplasic syndromes and myeloproliferative diseases; - the treatment of hypereosinophilic syndrome and chronic eosinophilic leukaemia in adults.

Parallel to this, Glivec was simultaneously given the green light by the FDA for five supplementary indications all corresponding with rare forms of cancer including a restrained therapeutic choice, dermato-fibrosarcoma, hypereosinophilic syndrome, severe lymphoblatic refractory leukaemia with Philadelphia chromosome as well as certain myeloproliferative syndromes. Glivec is now authorised by the USA in the treatment of seven pathologies of which five are rare haematological diseases and two are types of solid tumours.

Conversely, Novartis announced its decision on 23 October to withdraw its EMEA application to extend the marketing authorisation for Glivec. In February this year, the company submitted an application for the extension of marketing authorisation to include treatment of aggressive systemic mastocytosis in adults. Imatinib mesylate had been designated as an OMP for the treatment of mastocytosis on 26 August 2005.

The company's official reason for withdrawal was the consideration of the Agency's Committee for Medicinal Products for Human Use (CHMP) that the limited data given did not permit it to conclude on a positive benefit-risk balance of the drug's use in aggressive systemic mastocytosis.

Read EMEA press release (marketing authorisation extension); 16-18 Oct 2006

Read EMEA press release (Novartis withdrawal); 23 Oct 2006


Maturity of judgement in decision-making for predictive testing for non- treatable adult-onset neurogenetic conditions: a case against predictive testing of minors

International guidelines developed to minimize harm from predictive testing for adult-onset, non-treatable neurogenetic conditions such as Huntington disease (HD) state that such testing should not be available to minors. Some authors have proposed that predictive testing for these conditions should be available to minors at the request of parents and/or of younger adolescents themselves. They highlight the lack of empirical evidence that predictive testing of minors causes harm and suggest that refusing to test minors may be detrimental. This study focuses on the context of predictive test requests by adolescents younger than 18 years, and presents arguments and evidence that the risk of potential harm from testing such young people is sufficiently high to justify continued caution in this area. An Australian study based on a model of psychosocial maturity found that the 3 factors involved in maturity of judgement in decision making - responsibility, temperance and perspective - continue to develop into late adolescence. In addition, evidence that the prefrontal areas of the brain, which are involved in executive functions such as decision-making, are not fully developed until early adulthood. Combined with evidence of adverse long-term effects, from research with adults who have undergone predictive testing, these findings constitute grounds for retaining a minimum age of 18 years for predictive testing for non-treatable conditions. Continued maturity assessment research should help to reach a conclusion on this subject.

Clinical Genetics; 70(5) : 396-401; Nov 2006