Evaluation of Evidence Must Account for Scarce Data on Rare Diseases
Philadelphia, PA. (March 23, 2010) –The experts who make recommendations for genetic disease screening in newborns face a challenging task: To make conclusions based on the most authoritative available evidence, while considering gaps in the research on such rare conditions, as well as their human impact. An overview of the steps followed by the expert panels tasked with making these recommendations is presented in a special section of the April issue of Genetics in Medicine (www.geneticsinmedicine.org), the official peer-reviewed journal of The American College of Medical Genetics (ACMG). The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, and pharmacy.
The articles seek to communicate a review process that includes “careful assessment of the evidence, elimination of conflicts of interest, and transparency with significant public input throughout,” according to an introductory comment by Alan R. Fleischman, M.D., and Jennifer L. Howse, Ph.D., of the March of Dimes Foundation.
Effort Emphasizes ‘Unique Role of Unique Evidence’
The Secretary’s Advisory Committee on Heritable Disorders in Newborns in Children was chartered in 2003 to make recommendations to the Secretary of Health and Human Services regarding which genetic diseases should be included in newborn screening programs. A 2006 ACMG report recommended mandatory newborn screening for a core panel of 29 conditions, most of which are currently included in the newborn screening program of every state.
“The ACMG report was enthusiastically endorsed by the Secretary’s Advisory Committee as well as the American Academy of Pediatrics, the March of Dimes and other organizations,” Dr. Fleischman and Howse write. However, some commentators have questioned the methods used in making these recommendations, suggesting that the process “does not conform to contemporary standards of evidence-based decision making.”
To address these concerns, members of the Secretary’s Advisory Committee outline the process followed in making its recommendations. A key issue is the relative scarcity of data concerning most genetic diseases in infants, many of which are very rare. The threshold for evidence is “inherently different” than that for screening of more common conditions, such as cancer or cardiovascular disease.
The multi-step process includes assessment of the availability and quality of research evidence, the accuracy of the available screening tests, and the potential benefits of early detection and treatment. These are similar to the issues involved in screening for more common diseases. However, the process includes “more flexible criteria…to accommodate the data limitations stemming from the rarity of many of these conditions,” according to the Secretary’s Advisory Committee report.
In addition to considering published scientific evidence, the Committee seeks involvement of parent/advocacy groups, as well as experts who may have specialized knowledge in this rapidly-evolving field. In outlining the process and including the input of advocates and experts, the Committee has sought to develop “consistent and transparent strategies for evidence review.”
The special issue also presents updates on the prospects for new tests for specific genetic diseases, some of which may soon be evaluated by the Secretary’s Advisory Committee:
- A new and improved diagnostic test for fragile X syndrome-the most common inherited cause of mental impairment-which may soon make it practical to perform newborn screening and carrier testing for fragile X mutations.
- Progress in diagnostic testing for spinal muscular atrophy, a neurodegenerative disease that is the most common genetic cause of death in infants. Last year, the ACMG formally recommended population carrier screening for this condition.
- An update on testing for the 22q11 deletion syndrome: A highly variable condition that causes few problems in some children, learning disabilities or autism in others, and heart defects and seizures in others. Although no test is available yet, decisions about this condition are likely to set a precedent for the addition of other chromosomal diseases.
- Connexin-26-associated deafness, a common form of inherited hearing loss that worsens over time in many children.
Note to editors: Interviews with the lead authors available upon request by contacting Kathy Beal, Public Relations Director for the ACMG: phone 301-238-4582 or e-mail email@example.com. A separate press release has been issued providing more detailed coverage of the new test for fragile X syndrome.