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30 April 2008In recent weeks, the health department of New York State has issued letters warning companies which offer direct-to-consumer tests that they require a permit in order to carry out gene scans (see news source). Public health law in New York State prohibits clinical laboratories from providing direct-to-consumer tests without the intervention of a medical professional, unless the tests have been approved by the FDA for direct, over-the-counter sale to consumers (see guidance on Direct Access Testing). In California, health regulators are investigating companies that offer genetic tests without the presence of a physician (see news source). The need for an adequate framework to regulate genetic tests and companies that offer them direct-to-consumer is becoming an increasingly important issue.

A number of US organisations have called for policies to regulate genetic tests, especially those that are available direct-to-consumer. The American College of Medical Genetics has released a policy statement outlining five minimum requirements for genetic testing protocols. This follows a statement on direct-to-consumer genetic testing released by the American Society for Human Genetics containing similar recommendations, and a report from the UK Human Genetics Commission on the availability, marketing and regulation of genetic tests supplied directly to the public (see previous news story), both published in December 2007. The US Genetics and Public Policy Center has also recently called for tighter regulation of genetic tests in an article published in Science (see press release).

These organisations call for greater transparency in the evidence in support of genetic tests so that physicians and the public can make an informed choice. They also recommend health professionals to be involved in ordering and interpreting tests and a greater oversight of laboratories and companies that provide them.

29 April 2008In the last month there have been several new moves form the US intended to accelerate the pace of change in pharmacogenomics, the study of genetic influences on drug responses. The National Institutes of Health (NIH) has sought input from scientists, the pharmaceutical sector and other on challenges and barriers to pharmacogenomics research, on behalf of the Trans-NIH Pharmacogenomics Working Group, with a view “to highlight opportunities, reveal gaps, and aid in identifying specific, achievable goals that will advance the field” (see Request for Information).

Scientists from the NIH Pharmacogenetics Research Network have joined with Japanese scientists from the Centre for Genomic Medicine (part of the RIKEN Yokohama Institute) to sign a letter of intent for the creation of a new Global Alliance for Pharmacogenomics. The aim is to co-ordinate ongoing research efforts to identify genetic factors that influence responses to drugs, with initial projects including investigation of warfarin and selected drugs for breast and pancreatic cancers, as well as exploring genetic factors that affect drug-induced long QT syndrome.Yusuke Nakamura, director of the Center for Genomic Medicine said: "By bringing together our resources, we will advance the understanding of how changes in DNA affect our responses to medicines. Thus we can begin to realize the promise of personalized medicine" (see press release).

Meanwhile, in a move intended to harmonize pharmacogenomic definitions and guidance with Japan and the EU, the US Food and Drug Agency (FDA) has issued a new industry guideline for comment. E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories defines a genomic biomarker as a measurable DNA or RNA characteristic that is an indicator of normal biologic or pathogenic processes or a response to therapeutic or other interventions, and also notes that certain principles in the document may also be applicable to proteomics and metabalomics (see FDA news).

28 April 2008Our inheritance, our future, the 2003 White Paper on genetics, set out the UK Government’s first explicit policy commitments in the field of human genetics. Significant investment was announced in a range of areas including clinical genetic testing, pharmacogenetics research, service development, and education and training of health professionals. The Genetics Knowledge Parks programme aimed to look ahead to the scientific and policy developments that would be needed to bring genetics advances into mainstream health care and public health.

Five years on, the Department of Health has reviewed progress on the White Paper’s commitments. Some important achievements are highlighted, notably the development of a system for evidence-based evaluation of clinical DNA tests through the auspices of the UK Genetic Testing Network, the setting up of the National Genetics Education and Development Centre, and some improvement in the speed and capacity of clinical genetic testing services. The progress of White Paper-funded research projects in pharmacogenetics, service development and gene therapy is also described.

So far, so good, but the report, while acknowledging ‘future challenges and opportunities’ in a general way, fails to offer any real commitment or strategy, on the part of Government, to tackle these challenges. It is clear that five years is far too short a time for significant benefits from investment in genetics to have been realised. Genomics research is generating a flood of new information about associations between genetic variants and common diseases. What is needed is a rational approach, with realistic resources, for identifying and evaluating clinical applications of this information, and for steering health services through the process of change management that will be needed if validated new tests and interventions are to be successfully implemented.   

25 April 2008Amendments proposed last year in a review of the 1990 Human Fertilisation and Embryology Act contain a new provision in relation to fertility treatment that has offended members of the deaf community and raises important questions about government policies on embryo selection and serious disability. The controversy is centered on a new licensing condition proposed in clause 14(4) of the Human Fertilisation and Embryology Bill that would prohibit the selection of a ‘disabled’ embryo when a normal one is available. Embryos known to have a genetic abnormality (including a gender-related abnormality) that places them at ‘significant risk’ of ‘serious disability or illness’ are not to be preferred over those that are not known to have the abnormality. The same prohibition extends to the preference of persons with a genetic condition who might act as donors of gametes or embryos. The express intention of the clause, indicated in both the explanatory notes and proceedings in the House of Lords, was to prevent situations similar to those reported elsewhere in which deliberate attempts had been made to produce a deaf child through positive selection of embryos or donors.

The ensuing legal and ethical debate is far from theoretical for the deaf couple who wish to share their experience with a deaf child rather than a hearing one. Tomato Lichy and his partner Paula Garfield view their deafness as membership in a linguistic minority, rather than a serious disability, and attempts to prevent them from choosing a deaf child as discrimination violating their rights to equality and privacy. This view is opposed by members of the medical community, who have serious concerns about permitting the deliberate selection of deaf babies. Professor Peter Braude, director of the Assisted Conception Unit at Guy’s and St Thomas’ Hospital in London is quoted as saying that “This is the same as taking a normal child and deliberately making it deaf so that it can fit in with a community. I don’t see how that can be acceptable” (see Telegraph article). Neither is it a view that is accepted by some of those who campaign on behalf of the unhearing. The Royal National Institute for Deaf People (RNID) does not support the choice of deaf embryos over those who would not be born with hearing problems. Chief executive Jackie Ballard says that “No one should be forced into having genetic testing if they don't want it. But if they do, we would want the embryos without the gene to be implanted” (see BBC news).


Nevertheless, the outcry and media coverage has elicited a response from the Department of Health, which has reportedly agreed to drop any reference to deafness as a serious medical condition. The concession does not extend to removal of the general prohibition against preference of embryos with genetic conditions, but it could pave the way for a challenge in the House of Commons later this year as to whether deafness should be classed as a serious medical condition for the purposes of the Bill. If successful, amendment of the Bill might permit parents undergoing IVF treatment to choose an embryo that will develop into a deaf child.

14 Conditions of licences for treatment

(1)        Section 13 of the 1990 Act (conditions of licences for treatment) is amended in accordance with subsections (2) to (4).

…

(4)        After subsection (7) insert:

(8)       Subsections (9) and (10) apply in determining any of the following:

(a)      the persons who are to provide gametes for use in pursuance of the licence in a case where consent is required under paragraph 5 of Schedule 3 for the use in question;

(b)     the woman from whom an embryo is to be taken for use in pursuance of the licence, in a case where her consent is required under paragraph 7 of Schedule 3 for the use of the embryo;

(c)      which of two or more embryos to place in a woman.

(9)            Persons or embryos that are known to have a gene, chromosome or mitochondrion abnormality involving a significant risk that a person with the abnormality will have or develop—

(a)      a serious physical or mental disability,

(b)      a serious illness, or

(c)      any other serious medical condition,

must not be preferred to those that are not known to have such an abnormality.”

Clause 14(4) of the Bill (above) effectively means that a person with a genetic condition, at significant risk of serious illness or disability, may not donate eggs or sperm for IVF treatment if there is an existing donor without such a condition. It also means that an embryo with a genetic abnormality posing a significant risk of serious illness or disability must not be implanted if there is one available that does not, or is not known to, have the abnormality.

The case raises a number of legal and social questions about perceptions of disability and the parameters of reproductive choice. The ‘medical model’ of disability employed in the Act has been blamed by supporters of the deaf community for undervaluing people with genetic conditions, their contributions to society, and – in the case of the deaf couple – their unique language and culture. It is true that the choice PGD offers to parents is one based on purely medical criteria – while each embryo is equally valuable in human terms. It is also true that the objective of PGD is to provide families with a means of choosing to avoid hardships associated with serious physical limitations - and that parents are not obliged to have their embryos diagnosed prior to implantation. At the point at which the in vitro fertilization has taken place and diagnosis obtained, however, a crucial decision must be made. The decision is not about whether an unhearing child would be better off with hearing. It is about which of the embryos, each legitimate offspring of a couple, will be nurtured and raised, and which will perish. The decision involves an element of discretion that the government is apparently not content to leave entirely to the parents, and which the parents might justifiably consider their personal prerogative.

The legislation currently places some controls on the use of PGD, limiting the genetic characteristics that may be tested for, and thus the information upon which the selection is to be based. These parameters are not presently in question, but within them there is an issue over the right to make the actual selection. The legislation and the goal of medical intervention by PGD are based on a presumption, reiterated in clause 14(4), that the interests of the public are best served by avoidance of genetic abnormality and physical impairment, and propose to prevent any other result. The values that suffuse this presumption are a cause of concern for Tomato and Paula, who argue that their preferences should not be legislated and that the government should not be arbiters of their family life. 

Various arguments are being flung about in the debate as to the right of disabled parents to choose children like themselves. The right to privacy in such intimate matters, the right to family life and the right to equality as well as non-discrimination are being hailed. The public interests against which such individual rights must be balanced, apart from overarching public health questions and economic considerations, are not self-evident. There is unlikely to be a floodgates problem of people seeking to use PGD in this way. Still, the government may be committed in principle to a prohibition of deliberate preference of disabilities, and refocus the debate on whether deafness is outside of the scope of ‘serious disability’ or ‘serious medical condition’. The absence of definitions in the Bill is perhaps by design, providing a degree of flexibility to permit interpretative application in individual cases. Where however ambiguity is informed by a contextual understanding of the intention of the legislators - in this case the accompanying explanation that deafness was being targeted – the legislative interpretation must take it into account. By removing this reference the notes should have less (prejudicial) relevance for the interpretation of ‘serious disability’ in the context of individual PGD assessments involving deafness.

Given the current limitations of the treatment - the prevalence of IVF births is just 1% and PGD has a low success rate and high cost - one has to question the need for any change in the level of regulatory scrutiny regarding preferences in the selection process. While Tomato and Paula remain the exception to the rule, the case-by-case method for addressing such decisions may continue to be the most appropriate way of handling them.

23 April 2008New technologies that have a potential to impact on health services are in constant development, and adequate Health Technology Assessment (HTA) systems are needed in order to make evidence-based decisions on the benefits of new clinical tools. A recent report published by the European Observatory on Health Systems and Policies has identified areas which could lead to improvements in HTA systems; Ensuring value for money in health care: The role of health technology assessment in the European Union is based upon a review of HTA organisations and processes across Europe.

The authors concluded that improvements to HTA could be made through a number of mechanisms such as increased transparency and stakeholder involvement, assessment of existing technologies as well as new ones, assessing the timing of evaluations so that decisions can be made quicker and more effectively and the implementation of a system which allows re-evaluation of products based upon new information on clinical and health economics. Some of these recommendations are similar to those published in a report by the House of Commons Health Committee following an inquiry into NICE, the National Institute for Health and Clinical Excellence (see also NICE’s response).

Comment: The importance of the assessment of new biomedical tools and interventions is strongly supported by the PHG Foundation; one of the key strategic objectives is to promote the development of systems and policies for the proper evaluation of new technologies that arise from biomedical research, and many of our projects relate to evaluation of this kind; for example, see our work streams on the Evaluation and regulation of genetic tests and Promoting genetics in mainstream medicine.

Prompt and effective translation of emerging technologies into health service practice requires key steps of evaluation, assessment, appraisal and implementation following on from ‘bench to bedside’ research; the PHG Foundation suggests that in the UK, these stages are not optimally handled, with the Health Technology Assessment (HTA) scheme limited to evaluation and assessment, and not directly linked with policy development (see Genomic Medicine consultation response). Our aim as practitioners of public health genomics is to bridge the current gap between assessment/evaluation and clinical implementation, a gap which creates unnecessary delay at translating potentially valuable new technologies into clinical practice and better health.

22 April 2008In 1995 the House of Commons Select Committee on Science and Technology published Human Genetics: the Science and its Consequences, a report which showed for the first that UK politicians were becoming aware of new developments in genetics and their potential impact on health care. Publication of the report was followed, during the second half of the 1990s, by the establishment of the first Government advisory committees devoted to aspects of genetics policy.

More than a decade later, the Human Genome Project is complete and the Commons Science and Technology Committee is defunct, but its counterpart in the House of Lords has appointed a sub-committee to carry out an inquiry into Genomic Medicine, aiming to “provide an assessment of genome technologies and their actual and potential impact on clinical practice in the post-genome era”. The initial consultation stage of the inquiry, which has just closed, asked for evidence on issues ranging from the state of the science to how effectively it is being translated into new clinical tests and interventions, whether the existing regulatory framework is appropriate, and whether ethical, legal and social considerations are being adequately addressed.

In its response to the call for evidence, the PHG Foundation emphasises that, although genomic science is in a robust state, progress is much slower in evaluating the clinical and public health relevance of these scientific advances. There is insufficient recognition of, or resources for, the final stage of translation, which is not a research activity but a process of change management that includes knowledge integration and synthesis, knowledge brokering, stakeholder dialogue and consensus-building, clinical and public policy development, service review and reorganisation, education and training. These activities form the core of the work of public health genomics.

The PHG Foundation calls for a regulatory and policy regime that avoids ‘genetic exceptionalism’, instead treating DNA as one among several types of biomarker that may be used in the diagnosis of disease or estimation of disease risk. It points out that, in the context of common disease, the concept of ‘individualised medicine’ may be misleading. Advances in genomics are unlikely to lead to an ability to provide an individual with a precise, personalised prediction of drug response or disease risk. Rather, genomics will refine our ability to place that person within a band or segment of the population characterised by a particular array of diagnostic features or a particular average disease risk. This process does not differ in principle from the current practice of population stratification based on phenotypic features such as blood pressure or cholesterol levels.

Finally, the Foundation predicts that new service models and professional roles will need to be defined as genetics becomes integrated into mainstream medical practice, and routine genetic aspects of care are devolved to appropriately trained health professionals in other specialties.

The next phase of the House of Lords’ inquiry will be a series of public meetings and oral evidence sessions. The Committee expects to publish its final report, with the accompanying evidence, towards the end of 2008.

21 April 2008The Wellcome Trust Case Control Consortium (WTCC) has received £30 million to begin a new series of genome wide association studies, or GWAs (see press release). The venture, the largest study of genetics behind common diseases, will be funded by the Wellcome Trust and is a follow up to last year’s successful completion of a similar but smaller scale study (see previous news).

The previous study examined DNA samples from 19,000 individuals in order to gain a better understanding of the genetic factors involved in eight complex diseases. The current study involves a much larger sample number of 120,000, which will allow researchers to gain a better understanding of 25 diseases through examining single nucleotide polymorphisms (SNPs) and a comprehensive number of copy number variants (CNVs). Along with improved knowledge with respect to disease genetics, the undertaking will also look at the genetics of learning in children, and individual responses to statins.

20 April 2008The Organisation for Economic Co-operation and Development (OECD) has launched a public consultation on draft Guidelines for Human Biobanks and Genetic Research Databases (HBGRDs).

The success of research involving the human genome and resulting applications is dependent on the sharing of knowledge comprised of data, biological samples and information derived from the analysis of those samples. . The OECD guidelines are intended as a tool to assist both OECD and non-OECD economies with the development of policies for the establishment and operation of HBGRDs

The draft Guidelines have been developed by experts from OECD member states, including individuals from national and international HBGRDs, along with policy makers, researchers, lawyers, ethicists, and private sector representatives. They are intended for use by individuals and bodies involved in the governance, management and use of human biobanks and genetic research databases, and aim to provide both key principles and suggested best practices.

The OECD is inviting comments are invited from any member of the public, but there is a particular call for input from “public and private sector entities involved in the establishment, governance, management and use of human biobanks, genetic research databases, and collections; patient groups; researchers; and from experts involved in ethical, social, legal and financial fields” (see Frequently Asked Questions for more information). The deadline for submitting comments is 16 May 2008.

18 April 2008South Africa’s first Centre for Proteomic and Genomic Research (CPGR) has been officially opened (see news article). Based within the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, the centre houses a number of genomic and proteomic technology platforms which will be used to provide support and solutions to scientific communities both in industry and academia. The centre is also engaged in a number of research activities relating to both human and plant sciences such as identification of diagnostic markers for diseases like malaria and leukaemia, understanding the correlation between human genetic variation and drug response and the search for markers of pathogen resistance in maize.

Founded in 2006 through a grant provided by South Africa’s Department of Science and Technology, CPGR will contribute significantly to biotechnology in South Africa thereby helping to tackle many health problems faced by the country, as well as being a source of information about genomics for the public at large. It is hoped that public engagement and education about genomics and proteomics will assist in establishing adequate regulatory and evaluation systems for genomic and proteomic technologies (see keynote address by Minister Mangena).

15 April 2008There have been several recent international developments in stem cell regulation. On Friday 11 April, the Bundestag (lower house) of the German Parliament voted 346-228 to ease current legal restrictions on human embryonic stem (HES) cell research (see BBC news). Previously, German researchers have only been able to use HES cells harvested before January 2002, but now they will be free to use cells created up to May 2007. Germany has in general adopted a conservative approach towards controversial lines of medical research, but this latest move reflects concerns that their international scientific reputation could suffer if research is hindered by excessive regulatory burden.

Meanwhile, the UK National Stem Cell Network, which last week hosted its inaugural Annual Science Meeting in Edinburgh, has warned that the current status of the UK as a world leader in stem cell research will be in jeopardy in the absence of an increase in research funding in excess of £100 million. Professor Roger Pedersen said that the UK was at risk of being eclipsed by Germany and the US, both of which are investing heavily in this area (see Times Higher article).

A survey of public opinion on controversial work using human-animal hybrid embryos in the UK (see previous news) has suggested that 50% of respondents were in favour of the work, and of proposed legal amendments to facilitate such research (see The Times article)., A legal challenge has howeverbeen mounted by the UK Christian Legal Centre (CLC) against the decision of the Human Fertilisation and Embryology Authority (HFEA) to licence such research (see press release), on grounds that the 1990 Human Fertilisation and Embryology Act does not permit the creation of human-animal embryos. The 1990 Act has yet to besuperseded by amendments proposed by the Human Fertilisation and Embryology Bill, which are currently before Parliament.

In the US, a stem cell research advisory panel to the Food and Drug Administration (FDA) has been meeting recently to consider appropriate safeguards for potential use in clinical trials regarding new stem cell therapies on human subjects (see WebMD news). It is not clear whether these will be more rigorous than those applied to normal drug trials.

10 April 2008The Australian Capital Territories (ACT) legislative assembly is the latest Australian government body to lift its prohibition on human therapeutic cloning and pass the Human Cloning and Embryo Research Amendment Act 2008 (see press release). The state governments of Victoria (see previous news), Queensland (see ABC news), New South Wales (see previous news) and Western Australia (see ABC news) passed similar legislation last year, following the decision of the Australian federal government to lift its prohibition on cloning of embryos for stem cell research in December 2006 (see previous news). Reproductive cloning remains banned by federal, state and territorial law across Australia.

8 April 2008The UK Prime Minister Gordon Brown has announced a compromise whereby Labour Members of Parliament (MPs) will be permitted a free ‘conscience’ vote on selected elements on the Human Fertilisation and Embryology Bill currently before Parliament (see previous news); however, they are expected to support the Bill as a whole and not block its progress (see Ananova news).

Following this decision, and with less than a month until the Bill is scheduled to reach the House of Commons, UK scientists announced that they had successfully created the first human-animal hybrid embryos (see