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Posts Tagged ‘genetic testing

Science Policy Around the Web – October 24, 2017

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By: Jennifer Patterson-West, Ph.D.

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source: Max Pixel

Healthcare

Under Trump Rule, Nursing Home Residents May Not Be Able To Sue After Abuse

In October 2016, the Centers for Medicare and Medicaid Services (CMS) listed a final rule that prohibited pre-dispute agreements binding patients to arbitration. Subsequently, the American Health Care Association (AHCA) along with a group of nursing homes sued the CMS resulting in a preliminary injunction on the ruling. In June 2017, revised requirements for long-term care facilities that eliminated the prohibition were released by the CMS.

NPR journalist, Ina Jaffee, highlighted the major limitations of the revised requirement.  Jaffee points out that the new rule will make lawsuits by nursing home residents nearly impossible. The long-term implication is that many victims of negligent care will not have their cases heard by a jury.

The revised requirements require that “all agreements for binding arbitration must be in plain language” and that “the agreement must be explained to the resident and his or her representative in a form and manner they understand.” Senior counsel Kelly Bagby with the American Association of Retired Persons (AARP) notes that the requirement for plain language may be besides the point if that patients are required to sign these agreements.

An elder law attorney, Wendy York, noted that patients are given large stacks of papers to signs without fully comprehending the implications of what they are signing.   These patients are often recovering from a trauma, major surgery, or under the influence of mind altering medications while filling out paper work.  The new ruling would require that the “resident acknowledge that he or she understand the agreement,” however an agreement can be required for admission thereby limiting the option of a resident to refuse the agreement if they are in need of care without access to better accommodations.

These rulings could have larger implications on patient and patient advocate’s legal recourse after receiving substandard treatment. Although the new rules are an improvement on the status quo, they do not go as far as those previously proposed.  Unfortunately, it is our most vulnerable citizens that will have more limited protection under the current ruling. However, when the new rules will go into effect remains to be seen.

(Ina Jaffee, NPR)

 

Genetic Testing

A baby with a disease gene or no baby at all: Genetic testing of embryos creates an ethical morass

Increasing affordability of genomic testing has given people more access to information regarding their own genes and those of their potential offspring. Ethicists and experts are trying to consider the implications of genetic information moving into the hands of consumers. How can or should this information be used to make real-life decisions?

With respect to reproductive medicine, preimplantation genetic testing (PGT) can be used to evaluate potential diseases or disorders in in vitro fertilized (IVF) embryos.  In a 2013 federal report on fertility clinic success, PGT testing was reported for approximately 5% of IVF conceptions. However, experts suspect this figure underestimates the frequency of PGT testing and report that requests are growing. A survey of experts by STAT news relayed that “requests to transfer embryos with genetic anomalies are rare.”

The number of diseases that are tested for in prospective parents and embryos are expanding, some of these diseases have a more severe health impact than others. The question now is where to draw the line? Beyond the scope of severe diseases, patients may want to select an embryo with a specific trait.  In these cases, the physician has to decide what is within the ethical bounds of reproductive medicine.  For example, some members of the deaf or dwarfism community reject the notion that their DNA is categorized as a “genetic anomaly” and may desire a child that shares these traits.

Currently, there are no U.S regulation for these cases. However, regulations in the United Kingdom prohibit the transfer of embryos with severe abnormalities. To provide a foundation for clinicians facing these questions, an opinion was recently published from members of the American Society for Reproductive Medicine outlining potential rationales for providers to assist or decline to assist the transfer of embryos with genetic anomalies.

(Andrew Joseph, STAT)

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October 26, 2017 at 10:05 am

Science Policy Around the Web – October 20, 2017

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By: Patrick Wright, Ph.D

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Image: By Tom Varco [CC BY-SA 3.0], via Wikimedia Commons

Drug Pricing

California governor signs drug pricing transparency law

A recently signed bill in California aims to improve transparency of future changes to drug prices. The new law requires drug manufacturers to provide a 60-day notice of any upcoming price increases of more than 16 percent over a two-year period. It comes as an attempt to assuage public and political concern over increased pricing and price gouging practices in the pharmaceutical industry. For example, a new study in the Journal of Clinical Oncology reports that for a group of 24 FDA-approved, patented, injectable anticancer drugs, the mean cost increase was 18% over a mean follow-up period of 8 years following release, substantially outpacing inflation and unaffected by the addition of competition in the market.

This legislative venture is not without reproach, however. The Biotechnology Innovation Organization, the largest biotechnology industry trade group, issued a statement condemning the California bill, arguing: “This law will neither provide meaningful information to patients nor lower prescription drug costs”. Pharmaceutical companies and drug makers have also contended that whole price increases are not representative of the actual prices paid for medicines with discounts and rebates are considered.

On the other hand, an early positive consequence of the proposed legislation is that it has encouraged some companies including AbbVie Inc to voluntarily pledge a single annual price increase of under 10 percent on branded prescription medications in contrast to the industry-standard practice of biannual, double-digit cost increases.

This law is part of a larger pursuit across states to address rising healthcare and prescription drug costs. Another recent, analogous law in Maryland (House Bill 631) is aimed at price gouging of generic medicines, those drugs created after branded medicines are no longer patented, by companies not facing competition from other distributors; a plea by a pharmaceutical industry group was turned down by U.S. District Judge Marvin J. Garbis in September. Maryland and California are not alone. According to the National Conference of State Legislatures, at least 176 bills on pharmaceutical pricing and payment across 36 states have been introduced in 2017.

(Bill Berkrot, Reuters)

 

Genetic Testing

Gene-expression study raises thorny ethical issues

A National Institutes of Health-backed consortium, known as the Genotype-Tissue Expression (GTEx) consortium, aims to accumulate data about gene sequences and activity across 44 types of human tissue, collected from approximately 1000 anonymous deceased donors. It was established in 2010 to pursue questions related to the propensity of the same DNA sequence that is present throughout a human body to give rise to varied tissues; it aims to identify the genetic factors encoded by nucleotide variants that underpin different levels of gene expression in each of these tissues. To encourage widespread participation toward this cause, the data are made freely available to qualified scientists and companies.

As part of the collection process, loved ones representing the deceased donors are asked to consent on behalf of the donor to provide a medical history and collect genetic information and tissue from the deceased. However, the study was not designed to provide the results of genome sequencing and other tests to the loved ones of the deceased donors. This raises some important ethical considerations regarding informed consent and the potential moral obligations of scientists to donor families and loved ones. Susan Wolf, a lawyer and bioethicist at the University of Minnesota in Minneapolis, stated studies such as GTEx should allow for families to be identified if downstream research discovers a mutation, for example, that would dramatically predispose relatives to cancer if inherited.

Laura Siminoff, a bioethicist at Temple University, led a study to assess the feelings of donor families in GTEx on the entire process, finding that the stress of losing a family member may have clouded the extent of analysis and research pursuits for which they had provided consent; most recalled that they had agreed to donate their relatives’ tissue for research, but little else. Siminoff suggests that the informed-consent process could be expanded to included genetic counseling in tissue-donation projects of this nature.

Currently, three federal agencies play a role in the regulation of genetic testing: the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA), and the Federal Trade Commission (FTC). Generally, CMS is responsible for regulating the clinical laboratories performing genetic testing to ensure testing quality. The FDA regulates the safety and effectiveness of genetic tests and pharmacogenomics (the use of genomic information to predict patient response to a particular drug), as well as genomics tools in clinical research. Finally, the FTC regulates how tests are advertised. Interestingly, the collection of biospecimens from deceased individuals is not legally classified as human subjects research under the Department of Health and Human Services policy regarding the Protection of Human Subjects, but because potentially impactful genetic information could be uncovered in the study that is of direct significance to donor families, possible ethical implications still should be considered on their behalf.

(Ewen Callaway, Nature)

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October 20, 2017 at 9:02 am

Science Policy Around the Web – October 17, 2017

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By: Charles Wright, Ph.D.

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Source: Public Domain Pictures

Gene Therapy

FDA experts offer a unanimous endorsement for pioneering gene therapy for blindness

Gene therapy, an approach long hailed for its potential to cure intractable genetic diseases, finally has some successes in getting regulatory approval.  Recently, the U.S. Food and Drug Administration (FDA) approved the first-ever gene therapy treatment for a fatal brain disease.

Last week, another gene therapy approach—this time for a blinding disease that strikes in early-to-late childhood—also received endorsement by a 16-0 vote from the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee. The vote provides encouragement for patients suffering from Leber congenital amaurosis, type 2 (LCA2), which Voretigene neparvovec (Luxterna) from Spark Therapeutics aims to treat. However formal regulatory approval is still pending . Leber congenital amaurosis, although rare with an estimated prevalence of only 1:50,000 – 1:100,000, devastates vision at an early age. Newborns may show visual impairment immediately after birth, and most LCA patients lose most of their vision by the time they reach 20-30 years of age. Voretigene neparvovec aims to treat patients with mutations in the RPE65 gene, characteristic of LCA2, through gene therapy.

The recent string of successes in gene therapy comes years after the field struggled to rebuild itself after tragedy.  In 1999, the death of a participant in a trial to treat a rare metabolic disorder forced FDA to strengthen its oversight of gene therapy trials. With the first formal FDA approval for a gene therapy awarded just months ago, the recent approvals for other treatments since then suggests gene therapy may have reached a turning point.  In the future, gene therapy may be common for a variety of diseases.

If voretigene neparvovec receives FDA approval, it will be the first gene therapy treatment for a blinding disease.

(John Carroll, Science)

The Scientific Workforce

Why I’m pushing for a postdoc union

Postdoctoral fellows face a bevy of obstacles that threaten to derail even the most brilliant and committed young scientists from a research career.  Many postdocs unfortunately become intimately familiar with them in the lab; funding, publications, and tenure-track positions elude trainees and can keep postdocs from establishing themselves as independent researchers for years.  The harsh reality of the postdoc lifestyle often causes problems outside the lab as well.  Low pay, long working hours, and relationship strain all take their toll.

In response to these issues, some postdocs try to form unions to force academia to respond.  The subject of postdoc unions often pits researchers against university administrators, and the legal standing of postdoc unionization remains in flux.  Universities may claim unionization ultimately harms postdoc employment, as supervisors may write less than glowing recommendation letters for post-docs who missed work due to labor disputes. Nevertheless many postdocs feel unions may help provide a platform for receiving the benefits they need.

Brian Weitzner at the University of Washington (UW) in Seattle proposes collective bargaining rights for postdocs employed at UW campuses across the state.  In the past several months, while he and other postdocs prepare for a vote on whether to unionize, he talked with UW postdocs who share his concerns.  Fair pay, health insurance, and protection for victims of sexual harassment in the laboratory all motivate him to seek the establishment of a formal avenue with universities for resolving these and other issues.

UW postdocs are working with a local chapter of United Automobile Workers to navigate the steps needed to form a union. Their petition to vote is currently being reviewed by the Washington State Public Employment Relations Commission.

(Brian D. Weitzner, Science Careers)

Genomics

The rise and fall and rise again of 23andMe

Four years ago, the DNA-testing firm, 23andMe, teetered on the edge of oblivion.  Then, in 2015, 23andMe made the news again when it announced regulatory approval to sell a test for a rare genetic disease directly to the public.  Now, the company offers testing for 10 genetic diseases to consumers and continues to supply genomics data to collaborators to aid in drug development.

In 2007, 23andMe first gained prominence with its home-delivered kit that consumers could use to learn more about their genome.  After the company analyzed the data, costumers would receive information about their ancestry, predisposition to disease, and other miscellaneous facts such as whether they carried DNA variants that impacted their earwax consistency or urine smell after eating asparagus.  23andMe would also pool customers’ de-identified data together to analyze and sell to other pharmaceutical companies or research collaborators.

As 23andMe grew in popularity, critics became concerned that consumers were being overly impressed by advertisements indicating they could use their own genetic information to better inform personal health decisions even though many links between the DNA sequence variations reported by the test and disease remain dubious.  Alarmed by the possibility patients could make decisions about their health on information that had not been fully validated, FDA warned 23andMe it would need to provide evidence of the accuracy of the tests and ability of consumers to understand the results to continue marketing their kit as a health tool.  23andMe ignored the FDA’s warnings until the regulatory agency finally issued a cease-and-desist letter.

Since then, 23andMe decided to work with the FDA to approve the genetic tests included in its kit. The company can still only sell genetic tests directly to customers for a small number of diseases but is working with the FDA to expand its offerings to the general public.  In the meantime, the company still works with research collaborators to find new disease-relevant DNA variations, like those possibly involved in clinical depression.

Ultimately, 23andMe hopes its business model will lead to new therapies for disease.

(Erika Check Hayden, Nature)

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October 17, 2017 at 5:10 pm

Science Policy Around the Web – March 18, 2017

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By: Joel Adu-Brimpong, BS

By James Tourtellotte, CBP Today [Public domain], via Wikimedia Commons

Public Health Policy

Missing the Brush Strokes while Gazing at the Bigger Picture

Last Wednesday, the House Committee on Education and the Workforce approved a little-advertised bill called HR 1313, or the genetic testing bill, with partisan-line voting (all 22 republicans in favor and all 17 democrats opposed). Overshadowed by the highly publicized, contentious debate over the Affordable Care Act repeal-and-replace efforts, this bill has remained largely undetected by the media as it traverses congress. This genetic testing bill would not only enable employers to require their employees to undergo genetic testing but also allow employers access to the genetic information, according to an article by STAT news. Employees refusing such requests could be at risk for thousands of dollars in penalties.

Current legislation, including the Americans with Disabilities Act (ADA) and the 2008 Genetic Information Nondiscrimination Act (GINA), prohibit such authority by employers, preventing requests by employers for “underwriting purposes”, which include “basing insurance deductibles, rebates, rewards, or other financial incentives on completing a health risk assessment or health screenings.” Additionally, genetic information provided to employers must be de-identified and aggregated to protect individual identities.

The HR 1313 bill would circumvent current legislation by nullifying these protections as long as the genetic test requests are part of “workplace wellness programs.” Employers purport that the ADA and GINA are “not consistent with the well-established and employee protective wellness program regulatory framework under HIPAA.” They argue that the House bill will aid in aligning the ADA and GINA with laws about workplace wellness programs. Conversely, experts including Jennifer Mathis, director of policy and legal advocacy at the Bazelon Center for Mental Health Law, and Nancy Cox, president of the American Society of Human Genetics, have come out against the bill. In an opposition letter to chairwoman Representative Virginia Foxx (R-N.C.), and ranking member, Robert Scott, of the U.S. House Committee on Education and the Workforce, critics of the bill state that “Workplace wellness programs are fully able to encourage healthy behaviors within the current legal framework: they need not collect and retain private genetic and medical information to be effective. Individuals ought not to be subject to steep financial pressures by their health plans or employers to disclose their own or their families’ genetic and medical information.” Nonetheless, with the possibility of such infringement, we remain lost in the bigger debate surrounding Affordable Care Act repeal-and-replace efforts with little regard for subtle components like HR 1313. (Sharon Begley, STAT news)

Infectious Diseases

Here We Go Again? The Re-emergence of Yet Again, Another Arbovirus

The recent resurgence of arboviruses, or ARthropod-BOrne viruses, in the Americas is concerning. While the 1990’s saw the reemergence of Dengue and the West Nile, Chikungunya resurfaced in 2013 and, recently, Zika in 2015. With South and Central America and the Caribbean still reeling from the reemergence of these viruses, another arbovirus appears to be making a comeback. Over the past weeks, a fifth arbovirus has been detected. Per a perspective piece co-authored by Dr. Anthony Fauci, infectious disease expert and director of the National Institute of Allergy and Infectious Diseases, there are on-going outbreaks of yellow fever in Brazil.

As of February 2017, there have been 234 reported cases and 80 confirmed deaths, with many other infections pending investigation. In context, the number of reported cases currently exceeds previously observed rates of infection for this time of the year. Regionally, the reported cases appear localized to rural areas in southeastern Brazil, chiefly Sao Paulo, Espirito Santo and Minas Gerais. According to the article, current cases appear to be “sylvatic” or jungle cases, with transmission occurring primarily between forest mosquitoes and non-human primates. Thus far, there is no evidence to suggest human-to-human transmission via the infamous Aedes aeqypti mosquito. Humans currently serve as “incidental hosts.” However, the propinquity of the affected areas to major urban centers in Brazil, where routine coverage of yellow fever vaccination is low, is alarming.

Experts posit that the likelihood of spread to the continental United States is low. However, they caution, “In an era of frequent international travel, any marked increase in domestic cases in Brazil raises the possibility of travel-related cases [anywhere].” A particularly poignant example in the article is the December 2015 large urban yellow fever outbreak in Angola and subsequent spread to the Congo. This led to an exhaustion of the world’s emergency supply of vaccines for epidemic response, “prompting health authorities to immunize inhabitants in some areas using one fifth of the standard does in order to extend vaccine supply.” Amidst these critical times of global health crises, threatened cuts to U.S. global health support will likely be catastrophic for developing nations. (Madison Park, CNN)

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March 18, 2017 at 9:31 pm

Science Policy Around the Web – October 16, 2015

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By: Sylvina Raver, Ph.D.

Photo source: pixabay.com

Nutrition Policy

How agriculture controls nutrition guidelines

Every five years, the nutritional recommendations that help Americans make healthy dietary choices are revised to reflect the current state of nutritional and health science. Although only 4% of Americans adhere to these Dietary Guidelines for Americans (DGAs), DGAs have a huge impact. For example, physicians routinely use them to advise patients on how to stay healthy. DGAs also affect billions of dollars in government spending as they inform meal content for military personnel, those helped through the Women, Infants and Children (WIC) program and the Supplemental Nutrition Assistance Program (SNAP), and US children who are served public school lunches.

The process of updating DGAs involves compiling the recommendations of the Dietary Guidelines Advisory Committee (DGAC), a panel of scientific experts who distill thousands of scientific studies into an advisory report, with comments from the public and input from federal agencies. For the first time, the 2015 DGAC report recommended that sustainability of food sources be considered in the final 2015 DGAs. Sustainable diets are defined by the United Nations as those with “low environmental impacts which contribute to food and nutrition security and healthy life for present and future generations,” and the recommendation to consider sustainability is within the statutory bounds of the DGAC as defined in 1990. Proponents of the sustainability language emphasize the importance of considering the environmental impact of food production, and argue that nutrition is influenced by agricultural practices; for example, wild-caught fish or grass-fed beef is generally more nutritious than farm-raised fish or corn-fed beef. Opponents argue that sustainability is beyond the scope of the DGAC and accuses the committee of writing the recommendations from a political perspective rather than a scientific one.

Unsurprisingly, considering the extent of government funding that is influenced by the DGAs, the 2015 DGA revision process has come under constant attack by the agricultural industry. On Wednesday October 7, during a meeting of the House Committee on Agriculture, chaired by Representative Mike Conaway of Texas, Secretary of Health and Human Services Sylvia Burwell and Secretary of Agriculture Tom Vilsack conceded that the 2015 DGAs were not “…the appropriate vehicle for this important policy conversation about sustainability” as a “matter of scope,” and that sustainability would not be a factor in the 2015 DGAs. The sustainability debate will likely resume in 2020 when the DGAs are next revised.  (James Hamblin, The Atlantic; Kathleen Merrigan et al., Science; Sandra Hassink & Steven Stack, The Hill)

Scientific Funding

Neuroscientist team calls for a National Brain Observatory

A team of six influential neuroscientists has proposed the creation of a national network of neurotechnology centers that they’re calling the National Brain Observatory. The same group of scientists, dubbed “the Kavli six” due to their affiliation with The Kavli Foundation, is credited with drafting a proposal to map the activity of the living brain that would become President Obama’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative announced in Spring 2013. The first round of BRAIN funding was awarded mostly to individual labs or multi-lab research teams. In an opinion article published October 15 in the journal Neuron, the Kavli six call for the next step in the BRAIN initiative: a coordinated effort to synergize the discoveries made by the multiple individual laboratories funded by BRAIN. The scientists believe that the technological challenges facing neuroscience necessitate large investments in advanced technologies that are beyond the scope of any individual lab or research institution, similar to the national telescopes and particle accelerators used in the fields of astronomy and physics.

The goal of the National Brain Observatory proposal would be to expand shared access to four types of expensive technologies required to map the brain’s structure and activity: 1) large scale electron microscopes, capable of magnifying objects by more than 10 million times; 2) fabrication facilities to develop nanosized electrode systems capable of recording the activity of large networks of neurons with minimal damage to brain tissue; 3) new optical and magnetic resonance imaging (MRI) facilities to monitor the dynamics of neural circuits in real time; and 4) advanced electronic storage and computational data mining to collect and analyze vast amounts of data.

The Kavli six suggests that such technologies could arise from existing Department of Energy (DOE) National Labs around the country, such as Argonne National Laboratory in Illinois, or they could be housed in newly created facilities. The group argues that the experimental challenges being undertaken by the BRAIN Initiative, and by the neuroscience field at large, can only be surmounted through “highly coordinated, multi-investigator, cross-disciplinary efforts” such that a National Brain Observatory would permit. (Emily Underwood, ScienceInsider)

Genetic Testing

The crowdsourcing site that wants to pool our genomes

Two geneticists have launched a new crowdsourcing science project to collect the genetic data generated by direct-to-consumer (DTC) companies like Ancestry.com and 23andme.com. The project, called DNA.LAND, is a non-profit website created by Drs. Yaniv Erlich and Joe Pickrell and is affiliated with the New York Genome Center of Columbia University. DNA.LAND urges potential users to “Know your genome; Help science,” and the platform is designed to give participants ancestry and relationship data, as well as help to fill in missing sequences of DNA overlooked by DTC companies through a method called imputation. Although some of these functions are already provided by DTC companies, these companies compare users’ genetic information within individual company databases, and customers may miss out on connecting with relatives who have had their genetic information sequenced elsewhere. DNA.LAND compiles genetic information from multiple DTC companies, thus creating a dataset that is beyond the scope of anything amassed to date. To the extent to which users consent, scientists can then use this vast pool of genetic data to tackle research questions that require very large sample sizes. The project’s founders also envision linking DNA.LAND data with that from other sources, such as from activity tracking devices like Fitbits, or from social media activity that might indicate someone’s sleep patterns or mood fluctuations.

Privacy concerns are obvious. The site’s consent form contains minimal medical and legal jargon to describe guidelines that the founders say should lessen many of the privacy risks, such as not sharing personal identification information or genetic data with third parties without the user’s explicit permission. Still, the form contains the important caveat that the chance of a confidentiality breech is not zero and sharing data of this type carries inherent risks. Indeed, in 2013, Dr. Erlich and colleagues authored a study that revealed that men who have had their full genomes sequenced could be re-identified based on short DNA sequences found on their sex chromosomes.  To help ease users’ privacy concerns, both of DNA.LAND’s Principal Investigators adopt a “skin in the game” philosophy by making their own personal genomes publicly available. They are not alone; by October 15, less than a week after the site went live, nearly 6,000 genomes have already been uploaded. (Ed Yong, The Atlantic; Erika Check Hayden, Nature; Andrea Anderson, GenomeWeb)

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October 16, 2015 at 9:00 am

Science Policy Around the Web – October 14, 2015

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By: Amy Kullas, Ph.D.

photo credit: Cell Culture via photopin (license)

Reproducibility in science

Researchers do not bother verifying the identity of their cell lines

Despite being warned years ago, more than 50% of biomedical researchers admitted in a recent survey that they do not confirm the identity of their established cell lines. The confirmation process includes validating the species, tissue-type, and gender of the cells. Even those researchers that had confirmed their cells were labeled correctly, most did not use the ‘gold-standard DNA-based testing method.’ Contaminated cell lines waste valuable research funds and undermine research findings.

Unfortunately, not much has changed in cell line validation or cell culture practices in the past decade. Dr. Leonard Freedman, president of the Global Biological Standards Institute, said that “while support for change is strengthening, the scientific community has still not embraced cell authentication as an expected part of the research process.” He pointed to the issue of how cell identity directly contributes to data irreproducibility and encourages journals to refuse to publish manuscripts unless the authors describe how they validated cell lines used. Nature conducted an analysis from 60 manuscripts and found that only 10% of authors had validated their cell lines. Following that dismal finding, Nature and its associated research journals implemented a policy in May requiring “authors to check the cell lines used against a database of almost 500 known misidentified cell lines and to provide details about the source and testing of the cells.” (Declan Butler, Nature News)

Biomedical funding

NIH continues to reduce award funding

The National Institutes of Health (NIH) released a notice at the beginning of October, that continuing awards for fiscal year 2016 will be funded at a lower level than previously committed (approximately 90%). However given the NIH has been slated for a billion-dollar increase, the agency may return funding to 100% of the awarded amount after a final appropriation.

Global health

Polio remains endemic only in Pakistan and Afghanistan

On September 25, 2015, the World Health Organization announced that polio is no longer endemic in Nigeria, leaving wild poliovirus only spreading in Pakistan and Afghanistan. July 2015 marked one full year without a new case of polio being reported in Nigeria, taking the country and Africa close to being ‘certified polio-free’. This was a monumental accomplishment for Nigeria because as recently as 2012, Nigeria was credited for over half of all polio cases globally. The WHO wrote: “Eradicating polio will be one of the greatest achievements in human history, and have a positive impact on global health for generations to come.” (Sona Bari, Oliver Rosenbauer, and John Butler, World Health Organization News Release)

Genetic testing and scientific patents

Australia rules a genetic sequence is not a “patentable invention”

On October 6, 2015, Australia’s highest court ruled that “an isolated gene sequence is not a ‘patentable invention.’” This ruling mirrors legislation established in the United States, South America, and most of Asia. The European Union and Canada allow human gene patenting if the biological material has been isolated by a ‘technical process’.

In 2010 a cancer survivor, Yvonne D’Arcy, challenged patents over the BRCA1 and BRCA2 genes held by the Melbourne-based Genetic Technologies and the U.S. firm Myriad Genetics. BRCA1 and BRCA2 are human genes that encode tumor suppressor proteins, which can help repair damaged DNA and contribute to the stability of a cell’s genetic material. If mutations are present in one or both of these genes, the cells are more likely to divide and rapidly change, significantly increasing a woman’s likelihood of developing breast and ovarian cancers. Myriad had used the genetic information to develop diagnostic tests over which it and its international counterpart had a monopoly.

This decision allows hospitals in Australia to be free to perform genetics testing, perhaps even to develop their own assays, without many consequences from large biotech companies. However the biotech community feels differently and views the ruling as ‘blow to innovation’ while predicting the decision to have ‘significant negative impact’ on new and innovative medicines and innovations. Though Myriad’s patents have expired, the company estimates it had spent more than $1 billion over 25 years to develop its facilities and resources and the tests used on 2 million patients. (Leigh Dayton, ScienceInsider)

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October 14, 2015 at 9:00 am

Regulating laboratory tests for accuracy and patient safety

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By: Cheryl Jacobs Smith, PhD

On June 13, 2013, the Supreme Court ruled that Myriad Genetics did not own the sole rights to the genetic testing of genes involved in breast cancer susceptibility, BRCA1 and/or BRCA2 (1). Therefore, diagnostic companies and academic institutions could then create their own diagnostic tests surrounding BRCA1 and BRCA2. However, since the ruling, as more and more companies and academic centers are taking advantage of the “open market” on diagnostic tests, a question arises: Are all of these diagnostic tests appropriate for the clinic and safe for patient use?

The Food and Drug Administration (FDA) would certainly say no. In a document issued on October 3, 2014, the FDA outlined a draft guidance addressing gaps and areas of improvement related to the regulatory oversight of diagnostic tests (2). In the draft guidance, the FDA emphasized that the subset of in vitro diagnostic devices (IVDs) referred to as laboratory developed tests (LDTs), should have additional regulatory oversight to assure their safety and efficacy. Some recommendations include: adverse event reporting, an option to remove unsafe LDTs, critical evaluation of clinical validity and reproducibility of LDTs, and structured guidelines for informed consent.

Since 1976, the Medical Device Amendments (MDA), which amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act), established a rubric for the regulation of medical devices intended for human use (3)(4). It was amended to make explicit that the act include IVDs, and thus, LDTs. The definition of an IVD applies equally whether it is manufactured by conventional manufacturers or by individual laboratories. However, since the implementation of the MDA of 1976, the FDA has enforced applicable provisions with respect to LDTs under the FD&C Act at the manufacturer’s discretion. Thus, enforcement discretion for LDTs developed as a matter of general practice rather than by law.

The Centers for Medicare and Medicaid Services (CMS) has regulated LDTs (with research LDTs exempt) since 1988 under the Clinical Laboratory Improvement Amendments (CLIA—42 U.S.C. 263a) (5). Although all clinical laboratories must be properly certified to receive Medicare or Medicaid payments, CLIA has no direct responsibilities to either Medicare or Medicaid. CLIA governs the accreditation, inspection, and certification process for laboratories. However, the statutes of CLIA do not evaluate test validity prior to marketing, nor do they assess the clinical validity of a LDT. This regulatory gray area poses a couple of questions: Can the LDTs actually identify the biological events that the manufacturers claim? And, if so, with what accuracy in the tested population? These are very important questions when the result of a particular test could determine medical treatment. Therefore, although CLIA oversight is important, it alone does not ensure that LDTs are properly designed, appropriately manufactured, and are safe and effective for patient use. With the large regulatory gaps that still exist in the LDT market, how is it that this has gone on for so long without being addressed?

Initially, when LDTs were used to measure blood type or one or two biological markers at a time, CLIA accreditation was sufficient. However, due to changes in the complexity and use of LDTs, and with the advent of complex algorithms accompanied by computational analysis, CLIA requirements alone have become inadequate. Learning this information may make consumers uneasy to have any sort of test done by a medical office in the near future. Yet, is the current state of affairs of LDTs this dire?

I have been fortunate to witness the process by which an LDT is developed. From what I observed, the process appeared highly regimented, rigorous, and repeated to ensure accuracy and specificity of both the test and the instrument running the test. The diagnostic laboratory was not only CLIA-certified but was also certified by the College of American Pathologists (CAP) Laboratory Accreditation Program that “[…] test disciplines with the most scientifically rigorous customized checklist requirements.” (6) Under CAP-certification, laboratories must maintain the accuracy of test results and ensure accurate patient diagnosis, as well as have mechanisms in place to correct cited deficiencies. In that setting, the manufactured LDTs met the CLIA and CAP-certification requirements and included data on LDT specificity, accuracy, and clinical validity to discern between various biological conditions. Consequently, for this laboratory and others with CLIA and CAP-certification, additional oversight by the FDA could prove to be redundant and burdensome slowing down LDT production and availability, in turn potentially negatively impacting patient care. However, not every laboratory that manufactures LDTs conforms to this high level of scientific and medical integrity. Therefore, how can LDTs be regulated so that consumers can be confident in the methodology and reliability of LDTs without stifling LDT production and innovation?

The FDA proposes to amend the regulations surrounding LDTs by implementing a risk-based approach toward oversight of LDTs. Similar to how other medical devices are categorized into risk classes (I-III with I being the lowest risk and III the highest risk), LDTs would be classified based on risk to the patient and/or user and receive appropriate regulations commensurate to the risk level. With the exception of some LDTs solely used for forensic purposes and those used in CLIA-certified, high-complexity histocompatibility laboratories, those laboratories with high, moderate, and low risk LDTs would be required to enforce applicable regulatory requirements that include registration and listing, adverse event reporting, pre-market review, and quality system requirements. If the FDA guidelines become regulatory law for LDTs, patients would gain a comprehensive database of reliable LDTs increasing patient flexibility with whom they choose to do the LDTs and perhaps reduce costs if saturated markets are filled with reliable LDTs rather than a mixture of quality. Additionally, LDT manufacturers would be able to scrutinize tests more comprehensively instead of relying on word-of-mouth or anecdotal evidence to improve unreliable tests.

The suggested increased regulation of LDTs by the FDA may seem burdensome but would achieve a more comprehensive manner to regulate and equalize the validity of LDTs on the market. If anything, it would be helpful to have LDT pre- and post-market evaluations standardized as these measures uncover important medical device mishaps that frequently save patients from unnecessary harm or distress (7). The Diagnostic Test Working Group (DTWG), an independent group consisting of representatives from diagnostic manufacturers and clinical laboratories, suggested adopting some, but not all, of the FDA’s recommendations. Most importantly, the group stressed that this new legislation should require LDT manufacturers to register the LDT with the FDA but that additional oversight concerning sensitivity, specificity, and validity should be applied to LDTs only in the high risk class. Furthermore, DTWG suggested that the FDA should create an additional center for LDTs (8). The later should be seriously considered as FDA is excellent in drafting regulatory frameworks that ensure patient safety, but frankly lack the money and thus, people power to execute its regulations effectively. New LDT regulation may be needed, but without increasing the FDA’s budget to allow swift and effective execution of the FDA’s recommendations, this LDT legislation could ultimately just be black ink on white paper.

Written by sciencepolicyforall

June 10, 2015 at 9:00 am