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Posts Tagged ‘clinical trials

Growing Need for More Clinical Trials in Pediatrics

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By: Erin Turbitt, PhD

Source: Flickr by Claudia Seidensticker via Creative Commons

      There have been substantial advances in biomedical research in recent decades in the US, yet children have not benefited through improvements in health and well-being to the same degree as adults. An illustrative example is that many drugs used to treat children have not been approved for use by the Food and Drug Administration (FDA). Comparatively, many more drugs have been approved for use in adult populations. As a result, some drugs are prescribed to pediatric patients outside the specifications for which they have been approved for use, referred to as ‘off-label’ prescribing. For example, some drugs approved for Alzheimer’s Disease are used to treat Autism in children. The drug donepezil used to treat dementia in Alzheimer’s patients is used to improve sleep quality in children with Autism. Another example is the use of the pain medication paracetamol in premature infants in the absence of the knowledge on the effects among this population. While decisions about off-label prescribing are usually informed by scientific evidence and professional judgement, there may be associated harms. There is growing recognition that children are not ‘little adults’ and their developing brains and bodies may react differently to those of fully developed adults. While doses for children are often calculated by scaling from adult dosing after adjusting for body weight, the stage of development of the child also affects responses to drugs. Babies have difficulties breaking down drugs due to the immaturity of the kidneys and liver, whereas toddlers are able to more effectively breakdown drugs.

The FDA requires data about drug safety and efficacy in children before issuing approvals for the use of drugs in pediatric populations. The best way to produce this evidence is through clinical drug trials. Historically, the use of children in research has been ethically fraught, with some of the early examples from vaccine trials, such as the development of the smallpox vaccine in the 1790s. Edward Jenner, who developed the smallpox vaccine, has famously been reported to have tested the vaccine on several young children including his own without consent from the children’s families. Over the next few centuries, many researchers would test new treatments including drugs and surgical procedures on institutionalized children. It was not until the early 20th century that these practices were criticized and debate began over the ethical use of children in research. Today, in general, the ethical guidance for inclusion of children in research specifies that individuals unable to exercise informed consent (including minors) are permitted to participate in research providing informed consent is gained from their parent or legal guardian. In addition to a guardian’s informed consent, assent (‘affirmative agreement’) of the child is also required where appropriate. Furthermore, research protocols involving children must be subject to rigorous evaluation by Institutional Review Boards to allow researchers to conduct their research.

Contributing to the lack of evidence of the effects of drugs in children is that fewer clinical trials are conducted in children than adults. One study reports that from 2005-2010, there were 10x fewer trials registered in the US for children compared to trials registered for adults. Recognizing the need to increase the number of pediatric clinical trials, the FDA introduced incentives to encourage the study of interventions in pediatric populations: the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). The BPCA delays approval of competing generic drugs by six months and encourages NIH to prioritize pediatric clinical trials for drugs that require further evidence in children. The PREA requires more companies to have pediatric-focused drugs assessed in children. Combined, these initiatives have resulted in benefits such as improving the labeling of over 600 drugs to include pediatric safety information, such as approved use and dosing information. Noteworthy examples include two asthma medications, four influenza vaccines, six medications for seizure disorders and two products for treating migraines. However, downsides to these incentives have also been reported. Pediatricians have voiced concern over the increasing cost of some these drugs developed specifically for children, which have involved minimal innovation. For example, approval of liquid formulations of a drug used to treat heart problems in children has resulted in this formulation costing 700 times more than the tablet equivalent.

A further aspect that must be considered when conducting pediatric clinical trials is the large dropout rates of participants, and difficulty recruiting adequate numbers of children (especially for trials including rare disease populations) sometimes leading to discontinuation of trials. A recent report indicates that 19% of trials were discontinued early from 2008-2010 with an estimated 8,369 children enrolled in these trials that were never completed. While some trials are discontinued for safety reasons or efficacy findings that suggest changes in standard of care, many (37%) are discontinued due to poor patient accrual. There is insufficient research on the factors influencing parental decision-making for entering their child to a clinical trial and research into this area may lead to improvements in patient recruitment for these trials. This research must include or be informed by members of the community, such as parents of children deciding whether to enroll their child in a clinical trial, and disease advocacy groups. The FDA has an initiative to support the inclusion of community members in the drug development process. Through the Patient-Focused Drug Development initiative, patient perspectives are sought of the benefit-risk assessment process. For example, patients are asked to comment on what worries them the most about their condition, what they would consider to be meaningful improvement, and how they would weigh potential benefits of treatments with common side-effects. This initiative involves public meetings held from 2013-2017 focused on over 20 disease areas. While the majority of the diseases selected more commonly affect adults than children, some child-specific disease areas are included. For example, on May 4, 2017 public meeting was held on Patient-Focused Drug Development for Autism. The meeting included discussions from a panel of caregivers about the significant health effects and daily impacts of autism and current approaches to treatment.

While it is encouraging that the number of pediatric trials are increasing, ultimately leading to improved treatments and outcomes for children, there remain many challenges ahead for pediatric drug research. Future research in this area must explore parental decision-making and experiences, which can inform of the motivations and risk tolerances of parents considering entering their child to a clinical trial and potentially improve trial recruitment rates. This research can also contribute to ensuring that clinical trials are ethically conducted; adequately balancing the need for more research with the potential for harms to pediatric research participants.

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May 24, 2017 at 5:04 pm

Science Policy Around the Web – April 25, 2017

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By: Eric Cheng, PhD

Photo source: pixabay.com

FDA

FDA Nominee Gottlieb Tackles Vaccines, Trial Design at Hearing

The President’s nominee to head the FDA, Scott Gottlieb, MD, sat before lawmakers for his confirmation hearing before the Senate’s health committee. Gottlieb, a hospitalist and former FDA official, was questioned on many controversial topics on health.  On the topic of vaccines and autism, Gottlieb said, “I think we need to come to the point where we can accept ‘No’ for an answer, and come to the conclusion that there is no causal link between vaccinations and autism.”

On the topic of double-blind randomized trials as the “gold standard” for medical treatment research, Gottlieb was more cautious. He believed that there are more “opportunities to modernize how we do clinical trials in ways that aren’t going to sacrifice on the gold standard of safety and effectiveness. Perhaps there are ways to think of clinical trial constructs that don’t require the tight randomization that current clinical trials do.” What this suggests is a push towards more adaptive trials that would allow researchers to review results before a study’s endpoint and would allow changes to treatment groups in a study, which is in contrast to traditional randomized controlled trials.

Another less controversial but popular topic in the hearing was on opioid abuse. Gottlieb believed that opioid abuse is “a public health emergency on the order of Ebola and Zika” and that bolder steps will be needed to address this issue.

The committee will vote on whether to move Gottlieb’s nomination to the Senate floor after the Senate returns in late April from a 2-week recess. (Joyce Frieden, MedPage Today)

Healthcare Policy

Trump Administration Still Plans to Undo Parts of the ACA, Tom Price Testifies

Health and Human Services Secretary Tom Price made one thing clear during his testimony to the House appropriations committee: “The administration is still intent on dismantling parts of the Affordable Care Act even if Republicans lack the votes to rewrite it.”

Price discussed how, as the Health and Human Services Secretary, his department could scale back several federal mandates that include “essential benefits” in coverage to make insurance plans cheaper. He did not say if the administration will continue to provide cost-sharing subsidies for insurers, which has been a topic of discussion on items to change in the Affordable Care Act. However, removing subsidies will bring “significant premium increases,” said Michael Adelberg, a health-care principal at FaegreBD Consulting. He predicts that the removal of these subsidies will cause some insurers to drop out while the remaining insurers will seek rate increases to compensate.

Regardless of these discussions, the individual mandate remains in place with Price telling the panel, “So long as the law’s on the books, we at the department are obliged to uphold the law.” (Juliet Eilperin and Mike DeBonis, Washington Post)

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April 25, 2017 at 9:53 am

Science Policy Around the Web – April 18, 2017

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By: Nivedita Sengupta, PhD

Source: pixabay

DNA Testing

23andMe Given Green Light to Sell DNA Tests for 10 Diseases

On April 6th, the US Food and Drug Administration (FDA) approved the first at-home genetic test kits, which can be sold over the counter in pharmacies, to determine the risk of developing certain genetic diseases. Since 2006, 23andMe, a company based in California, has been analyzing DNA from saliva samples of its customers to provide genetic insights into their risk of developing 240 different diseases and disorders. However, in 2013, FDA was concerned about customers using test results to make medical decisions on their own, and ordered 23andMe to halt the service. In 2015, FDA eased some of the restrictions and allowed the company to reveal to their customers only the information regarding genetic anomalies that can be transferred to their children, and not any information about the person’s own disease risk.

23andMe now has permission to inform its customers about genetic mutations that are strongly associated with a small group of medical conditions such as Parkinson’s disease, late-onset Alzheimer’s disease, celiac disease and a hereditary blood-clot disorder called thrombophilia. However, it should be noted that the results from these tests are not equivalent to a medical diagnosis, as the development of a disease is also influenced by a person’s family history, lifestyle and environment.

The decision made by the FDA paves the way for a wave of do-it-yourself diagnostic tests, which will be flooding the market in the coming years. “It’s a watershed moment for us and the FDA,” says Kathy Hibbs, chief legal and regulatory officer at 23andMe. However, there are concerns regarding the limits of medical knowledge among common people to understand and interpret the results and the limitations of these tests, which could lead to misinterpretation of the results and complications. (Amy Maxmen, Nature News)

Neonatal Care

Giving Newborns Medicine is a Dangerous Guessing Game. Can We Make it Safer?

Medical emergencies in neonates are on the rise. It might be surprising for many parents to know that 90% of the medications administered in a neonatal intensive care unit are not medically approved by the FDA for use in newborns. Neonates are routinely treated with drugs that are not adequately tested for safety, dosing, or effectiveness. This is a global problem, and many factors contribute to it. Firstly, parents and doctors are afraid of enlisting newborns in clinical trials. Secondly, pharmaceutical companies are afraid to test drugs on neonates as the risk of liability is very high. It is also a small market, so pharmaceutical companies may not make money by getting drugs approved for neonates.

In 2015, an FDA funded nonprofit organization launched two global efforts to encourage clinical trials in newborns. One of which is the International Neonatal Consortium (INC), which published a guide to clinical trials in neonates last year. Dr. Jonathan Davis, Director of INC said, “We’ve got to do something.” Without information on drug data for newborns, “we can’t be certain which drugs, in which doses, to use when.” Under the current system, doctors are making decisions based on either anecdotes or intuition, which essentially means that every sick newborn is an uncontrolled, unapproved study without the guarantee of seeing improvement. No data collection is done, thus not providing any information for treating other infants around the world.

Physicians often take decisions by scaling down from how medications are used in adults. But this can be fatal and lead to disasters as we have seen in the past, with the use of the antibiotic chloramphenicol in the 1950s, and the preservatives benzyl alcohol and propylene glycol in the 1980s. Infants are not tiny adults, and they adsorb, metabolize, and excrete drugs in different ways than adults. The majority of studies done in neonates in recent years have not been able to establish efficacy. More studies need to be done, and this requires proper designing of clinical trials with reduced risk, and eliminating unnecessary interventions. (Megan Scudellari, STATNews)

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April 18, 2017 at 10:45 am

Science Policy Around the Web – January 24, 2017

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By: Leopold Kong, PhD

Landfill by Dhscommtech at GFDL, via Wikimedia Commons

Environment

New Discovery Could Lead to a Safer Solution to Plastic Pollution

Polyethylene terephthalate (PET) is a commonly used resin of the polyester family used in the fibers for clothing and liquid containers. In 2015 alone, 56 million tons of PET was produced. Although recyclable, with 1.5 billion pounds recovered annually in the United States, PET is not biodegradable and is a major presence in landfills. Screening 250 samples of contaminated soil, waste water and sludge from a bottle recycling factory for microorganisms that can grow on PET, a team of Japanese scientists has discovered a bacterium, Idoenella sakaiensis, that can break down this tough plastic. Recently spotlighted as a major breakthrough of 2016 by the American Chemical Society, research on the bacterium continues as scientists seek to unlock the mechanism behind the biodegradation pathway that was previously thought to be impossible. Professor Kenji Miyamoto, one of the study authors, said, “This is the first PET-degrading bacterium found [with potential] to develop a new and nature-friendly system”. (Research Highlights, Keio University).

Biomedical Research

Trump Asks NIH Director Francis Collins to Stay On

Last Thursday, on the eve of the inauguration, the National Institutes of Health (NIH) announced that Dr. Francis Collins has been asked to continue his role as NIH director by the Trump administration for an unspecified time. This eleventh hour development came as Collins received back the letter of resignation he had sent late last year, something all presidential appointees do. If asked to stay on through this presidential term, Collins, part of Obama’s science ‘dream team’, would be the first NIH director since the 1970s to be chosen by two presidents.

Ezekiel Emanuel, a bioethicist at the University of Pennsylvania said, “In general, I think more than eight years has not been a good idea. There’s a cycle, and eight years is hard to have new ideas and new energy.”  Nonetheless, Collins, a National Academy of Sciences member who led the human genome project and a highly vocal Christian apologist, would serve as an effective bridge between the research community and the new Republican administration to secure much needed funding for basic research. Tony Mazzashi, senior director for policy and research at the Association schools and Programs of Public Health in Washington DC said, “ I think everyone in the research community will be thrilled.” (Jocelyn Kaiser, Science)

Public Health

Novavax Starts New Clinical Trial in Bid to Prove Failed RSV Vaccine

Respiratory Syncytial Virus (RSV) is a significant public health burden, infecting almost all children by age 2, with 5 to 20 out of 1,000 requiring hospitalization and with a mortality rate of 8 to 34 out of 10,000. Unfortunately, the development of an effective vaccine has been challenging. In the late 1960s, an RSV vaccine for infants devastatingly failed clinical trials with 80% of children receiving the shot being hospitalized. Recent advances in immunology and the RSV vaccine target has led to a new generation of potentially safer and more effective vaccine candidates from industry giants Novavax, GlaxoSmithKline, Global Vaccines, AstraZeneca and MedImmune. Also being explored is vaccination of expectant mothers to protect infants.

However, the field took a hit last year when Novavax’s candidate vaccine failed its phase 3 clinical trials, resulting in a 30% layoff of its workforce. Nonetheless, last Thursday, the company announced that it has started a new phase 2 trial on older adults in the southern hemisphere.  “We expect the results from this trial to inform the next steps in our older adults program and would ensure we maintain our leadership position in this very attractive market opportunity,” said Stanley Erck, president and CEO of Novavax. (Tina Reed, Washington Business Journal)

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January 24, 2017 at 10:04 am

Streamlining Human Research by Centralizing Review: Could It Slow Things Down?

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By: Leopold Kong, PhD

Source: NIH Image Gallery on Flickr, under Creative Commons

       Human research in the United States in the form of clinical trials and other scientific studies has been regulated by Institutional Review Boards (IRBs) since 1974 after the passage of the National Research Act. The initial policies were inspired by the Nuremberg Code, a set of international research ethics principles developed in the aftermath of the second world war when Nazi medical officers conducted large-scale human experimentation atrocities. Policies that regulate IRBs in the United States are codified in the Common Rule, which mandates requirements such as membership qualifications and guidelines for protections of certain vulnerable research subjects. Although the Common Rule has not been modified since 1991, the changing face of medical research has led to recent proposals to improve the efficiency, accountability and qualification of IRBs. What has motivated change? The following situations may be illustrative.

In November 2015, the consumer advocacy group Public Citizen, and the American Medical Student Association contacted the Office for Human Research Protections (OHRP) to criticize two studies on how longer-than-21-hour shifts of first-year medical students may affect 30-day patient mortality rates. Public Citizen noted that even though the studies forced new residents to work “dangerously long shifts”, placing all involved in danger, they were readily approved by IRBs. Similarly, IRBs approved a study on the hazards of pediatric exposure to lead paint, in which researchers did not clearly reveal to households that they detected high levels of lead in their homes, resulting in neurological problems for at least one child. Also, a publication last year in the European journal Acta Informatica Medica found that only 26.5% of individuals in IRBs correctly answered 11 simple True or False questions designed to test understanding of study design and ethics. Part of the problem may be research fatigue since, according to OHRP, there are only about 3,500 registered IRBs that review more than 675,000 research protocols annually. Inefficiencies in the review process may further exacerbate the situation.

Late last year, Kathy Hudson and Francis Collins, the Deputy Director for Science, Outreach and Policy at the National Institutes of Health (NIH), and the Director of the NIH, respectively, published a Perspective in the New England Journal of Medicine on the proposed revisions to the Common Rule. In order to bring the Common Rule into the 21st century, the revisions will focus on implementing broad biospecimen consent, enhanced privacy safeguards, streamlined IRB review, and requirements for more agencies to follow the Common Rule. One of the more interesting and key revisions to improve review efficiency, the requirement for a single IRB (sIRB) for multisite studies, will be implemented on May 25, 2017. The rest of this essay focuses on this proposed change.

The time it takes for a clinical trial protocol to be reviewed by an IRB depends on the type of review, and varies from location to location. For example, a protocol can be deemed exempt, which might take only 1-2 weeks of review, expedited, which might take a few weeks longer, or be required for full review, which would take even longer. Re-evaluations are required if the protocol is sent through expedited or full reviews every year, after any changes to the method, or after any adverse event in the study. The review generally evaluates proof of human subjects’ training, consent, recruitment materials, and data collection instruments, as well as individual conflicts of interests, all of which may depend on the specific population studied and local restrictions. However, clinical trials are increasingly spread across multiple sites in order to recruit enough people for their studies. Under the current rule, each site must conduct local reviews of the same protocol independently of each other, potentially causing delays due to unneeded redundancies. “The problem that this [proposed sIRB] policy was trying to solve was that we were seeing delays and complications in moving research forward in a way that wasn’t providing commensurate protections for human research participants,” said Carrie D. Wolinetz, NIH associate director for science policy, to Bloomberg BNA.

From December 3, 2014 to January 29, 2015, the NIH received 167 comments from individual researchers, academic institutions, IRBs, advocacy groups, scientific societies, healthcare organizations, Tribal National representatives and members of the general public on the sIRB proposal. Many of the comments were highly positive and supportive of the revision. For example, the Federation of American Societies for Experimental Biology (FASEB), which represents over 120,000 researchers across 27 scientific societies, stated that “[t]his change would facilitate collaborative review arrangements and reduce the obstacles that investigators encounter when embarking on multi-center projects.” David M Pollock, the president of the American Physiological Society, added further support, commenting that the current rule results in “lack of uniformity” while the proposed changes may reduce administrative burden, and improve efficiency and quality of review.

However, many of the comments displayed reservations and harsh criticism. For example Harry W. Orf representing Massachusetts General Hospital was skeptical that the costs to move into the sIRB system would outweigh the benefits, commenting “there is currently little research or data to demonstrate that these potential benefits will materialize.” In much stronger terms, Curtis Meinert from the Johns Hopkins Bloomberg School of Public Health stated,” [t]he expectation is that the change will save money. Good luck on that. The reality is that the change will increase costs given what IRBs of record have to do to acquire the necessary assurances and certifications. The expectation also is that the single IRB will shorten the time to start, good luck on that one also.” Meinert and others, including the Human Subjects Protection Branch at Walter Reed Army Institute of Research, pointed out that the time it takes to start a study is mainly determined by other factors such as the time it takes for investigators to agree on a protocol, not IRB review. Meinert also warns that, “A likely unintended effect of the one IRB requirement is to further diminish the means and incentives for individual investigators to propose and initiate multicenter studies..” Finally, some communities also viewed the revision as a threat to local autonomy and representation. For example, Bill John Baker, the Principal Chief of the Cherokee Nation, commented, “Tribal IRB members have firsthand knowledge of local tribal customs, cultural values, and tribal sensitivities. If Tribal IRB members are not able to participate […] our citizens are affected by persons who are not sensitive to their distinctive needs.”

Analysis of all comments made regarding sIRB by the Council on Government Relations indicated that 51% opposed the proposal while 42% supported it and 6% offered qualified support. Interestingly, most commercial IRBs, which might be more favorably biased towards the needs of industry sponsors, supported this change. A breakdown of the numbers indicates that while the majority of advocacy groups, professional societies, disease registries and individual researchers supported the change, 89% of universities and medical centers, the organizations that are directly involved with clinical trials and representing thousands of researchers and medical support staff, opposed it. “The spirit of the changes are well intended, but it fails to address the fact that roles and responsibilities of the IRB have expanded beyond those initially dictated when the use of IRBs were first formed“ says Annika Shuali, certified clinical research coordinator at the University of Virginia.

Clearly, reforms are needed to update the aging IRB system. In theory, centralization through the sIRB may improve efficiency. However, in practice, the complexities and details of conducting clinical trials at specific sites such as resolving individual conflicts of interest, being compliant with local regulations, and accounting for the specific rights of certain populations make centralization extremely difficult. To address these site-specific issues, local IRB’s may still need to be in place, but now required to communicate to the sIRB, potentially increasing administrative burden, which undermines the original motivation to streamline review. Hopefully, the sIRB revision to be implemented next year will be further revised to address the critiques from the majority of the community.

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December 3, 2016 at 11:46 am

Science Policy Around the Web – October 25, 2016

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By: Nivedita Sengupta, PhD

Source: pixabay

Clinical Trials

EMA becomes first major drugs agency to publish clinical-study reports online

On 20th October, the London-based European Medicines Agency (EMA) published details of the full clinical-trial data that it received from pharmaceutical companies, some 100 clinical reports, about two EMA-approved medicines, carfilzomib, a cancer drug, and lesinurad, a gout treatment. The disclosures make the EMA the first major drug regulatory agency to completely publish the results of clinical investigations that drug developers submit while applying for the agency’s approval to market medicines in the European Union. “These clinical study reports (CSR) are much more detailed than the papers that drug firms publish in scientific journals. It includes both positive and negative results, and details of drugs’ adverse effects,” says Larry Peiperl, the chief editor of PLoS Medicine.

Under the rules the EMA brought in six years ago, it had released results of such studies only if third parties asked for them using freedom-of-information requests. However, those rules allowed some drug firms to drag the agency to court to try to prevent their data from being released, arguing it as commercially confidential. However, patients and clinicians have waited long, and about 700 medical and patient organizations had lobbied for clinical data release under the All Trials campaign. “The EMA’s CSR policy adopted in 2014 will benefit both academic research and the practice of medicine as a whole,” says EMA executive director Guido Rasi. It will help academicians to independently re-analyze data even after a medicine has been approved, and will help drug developers to learn from the experiences of others.

The EMA intends to release all CSRs in applications that were submitted since 1st January 2015. It will only edit some commercially confidential information like individual patient data before release. After the clearance of backlog, the EMA says that it will offer public access to around 4,500 clinical reports each year.

Some drug firms are still resisting the release of their data by the EMA. In the latest legal battle this July, an interim judicial EU court order blocked the EMA from releasing toxicity studies on a veterinary medicine called Bravecto (fluralaner), and clinical-study reports on Translarna (ataluren), a treatment for Duchenne muscular dystrophy. The two drug firms concerned, Intervet and PTC Therapeutics, argued that the release of data would infringe on their rights to protect commercially confidential information. However, the EMA has appealed against both decisions on 29th September, and says that it sees the cases as a test of its policy. (Alison Abbott, Nature News)

Biotechnology

In a first, mouse eggs grown from skin cells

For the first time, stem cell researcher Katsuhiko Hayashi of Kyushu University in Fukuoka, Japan, and colleagues have reprogrammed fibroblasts from the tip of an adult mouse’s tail to make eggs, which upon fertilization grew into healthy mice. Earlier, adult body cells were reprogrammed to generate stem cells (induced pluripotent stem cells – iPSCs), which were further induced into becoming a wide variety of other cells but never eggs. Egg cells are much trickier as they represent ultimate flexibility which can create all the bits and parts of an organism from raw genetic instructions. “This is very solid work, and an important step in the field,” says developmental biologist Diana Laird of the University of California, San Francisco. This major development could make it possible in near future to study the formation of gametes — eggs and sperm — an unknown process that takes place inside fetuses. Moreover, if the experiments gets extended to human cells, it could make eggs easily available for research and may eventually lead to infertility treatments.

In this experiment, Hayashi and colleagues made artificial ovaries by extracting ovarian support cells from albino mouse embryos, which were then mixed with primordial germ cell‒like cells created from tail-tip skin cells from a normally pigmented mouse. After 11 days of maturation followed by fertilization, the eggs were transplanted into the uteruses of female mice. Six pups with dark eyes were born, indicating that they came from the tail-tip eggs and not eggs accidently extracted from the albino mice along with the ovarian support cells. The baby mice grew up apparently healthy and have produced offspring of their own.

As ovarian cells from mouse embryos were still needed to support the growth of eggs in vitro this could be a potential problem when trying to replicate the experiments in humans. “It’s yet unclear how support cells in ovaries foster egg development. Researchers can’t yet reproduce the supporting cells in the lab and so need to get those cells from embryos,” Hayashi says. (Tina Hesman Saey, ScienceNews)

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October 25, 2016 at 10:55 am

Science Policy Around the Web – September 27, 2016

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By: Nivedita Sengupta, PhD

Source: pixabay

Alzheimer’s Disease

Larger studies are under way to test whether the promising early data holds up

Recent clinical trials reported that the drug “Aducanumab” might remove toxic amyloid-β proteins thought to trigger Alzheimer’s disease from the brain. In the study involving 165 people, 103 patients received the drug once a month for 54 weeks and the other group received a placebo. Patients receiving infusions of aducanumab experienced a reduction in the amount of amyloid-β in their brains, which was in accordance with the findings of a pretrial mouse study in which the drug cleared amyloid-β plaques from the animals’ brains. “This drug had a more profound effect in reversing amyloid-plaque burden than we have seen to date,” says psychiatrist Eric Reiman, executive director of the Banner Alzheimer’s Institute in Phoenix, Arizona.

Whether aducanumab works to ameliorate the memory and cognitive losses associated with Alzheimer’s is currently under phase III clinical trials. Scientists have debated for years whether accumulation of amyloid-β causes memory loss and other symptoms of Alzheimer’s. This trial is in favor of the “amyloid hypothesis”, and suggests that elimination of the protein might alleviate the symptoms. In the past, other Alzheimer’s drugs have looked promising in early-stage trials, but ended in failure and even caused deaths of patients because of brain inflammation. Aducanumab also showed abnormalities on brain-imaging scans but it was in less than one-third of the patients. Hence, to avoid death of participants, researchers closely monitored such anomalies in these Alzheimer’s trials. All of the reported imaging abnormalities eventually disappeared in about 4 to 12 weeks, and no patients were hospitalized.

Patients who received higher doses of the drug, or who had genetic risk factors for Alzheimer’s, were more likely to develop the brain anomalies. Accordingly, Biogen — the company that makes aducanumab —adjusted the drug’s dosage and the monitoring schedule for people with genetic risks for Alzheimer’s in its phase III trials.

Aducanumab is a bright spot in the field of Alzheimer’s therapeutics after years of failed antibody and other types of drug trials. “This is the best news we’ve had in my 25 years of doing Alzheimer’s research, and it brings hope to patients and families affected by the disease,” says neurologist Stephen Salloway of Butler Hospital in Providence, Rhode Island, who was on the team that ran the initial trial. (Erika Check Hayden, Nature)

Clinical Trials

Investigators are now required to disclose all clinical trials, whether successful or not

On 16th September 2016, the US Department of Health and Human Services (HHS) and the US National Institutes of Health (NIH) announced the new rules for clinical-trial disclosures. According to the new law, it is required that all researchers must report the design and results of all clinical trials whether successful or not. The revised law also empowers the government to enforce penalties for those who fail to comply. The new rule will be effective from 18th January onwards and researchers have 90 days to comply. The disappointing results of clinical trials will no longer remain unpublished, and the new rule intends to crack down on the large number of clinical trials that are conducted but never reported. Robert Califf, head of the US Food and Drug Administration (FDA) says, “A lot of major universities just miss the point that if you do an experiment on a person and get consent, you really have the obligation to make the results known.”

The old rule mandated that researchers conducting trials with human subjects had to register their study with the HHS website, ClinicalTrials.gov, before starting their work, and should follow up with information about their methods and results. But there were many exceptions and loopholes which created a lot of ambiguity. This allowed researchers to avoid reporting all the trials, particularly the failed ones. Christopher Gill, a health researcher at Boston University in Massachusetts says, “This can bias the literature and obscure important information on whether an experimental therapy is harmful. From the perspective of consumers and science, failures are as important as successes”.

Under the new rule, all trials must be registered on ClinicalTrials.gov within 21 days of enrolling their first patient and researchers can no longer wait for the results of their trials to report their data. Additionally the NIH’s companion rule edicts that NIH-funded researchers have to register phase I trials and also trials that do not involve an FDA-regulated product, such as behavioral interventions. Further changes dictate reporting the details of plans to conduct trials, outlining the statistics to be used to analyze the results, and revealing any changes in the protocol over the course of the study. The final HHS rules will give regulators a greater ability to enforce existing regulations, because many studies of drugs that are eventually licensed are still not reported. (Sara Reardon, Nature)

Income Inequality

Wages for top scientists are shooting skywards while others are being left behind

Income inequality in science is in the rise and is evident in all universities across several countries. The salary gap between elite scientists and those toiling in the benches is expanding over the past few decades. Limited data on the salaries of scientists is available making it difficult to determine the full extent and causes of income inequality. “But the gap in wages has reached a point at which it could be driving talented young people away from careers in academic science”, says Richard Freeman, an economist at Harvard University in Cambridge, Massachusetts. The results of Nature‘s 2016 salary survey also support this concern.

One of the metrics used to measure disparities in salaries is the Gini coefficient in which 0 means everyone earns the same and 1 indicates maximum inequality. In 2012, economist Paula Stephan found that the Gini coefficient has more than doubled between 1973 and 2006 in most fields and faculty ranks in science, with the biggest increases in the life sciences. In contrast, it grew only 35% for full-time male earners in the United States and 18% for US households.

A major issue responsible for the rise of the Gini coefficient is the doubling of the National Institutes of Health’s budget during the late 1990s and early 2000s. This created competition among institutions for a small pool of top-ranked, grant-winning scientists. Everybody wanted to employ the most productive scientists who could bring in grants thus driving up the salaries. “One way for universities to minimize risk is to pick someone who is a demonstrated winner,” says Donna Ginther, a labour economist at the University of Kansas. Like the US, in the UK too, the salaries of top-earning professors have been pulling away from the pack since the late 1990s. An analysis of full-professor salaries in UK in July suggested that low ranking universities, to improve their REF (Research Excellence Framework – an assessment, done by UK funding agencies roughly every five years) performance, are offering high salaries to recruit researchers with high-quality papers to boost their scores. A similar trend is seen in other countries like China and Germany.

On the other end of the salary spectrum, there is little pressure to boost pay. With grants getting harder to win, labs are employing low-cost workforce to maximize research output. This labor environment benefits from the willingness of postdocs to sacrifice income for a chance at an academic research career. Even those lucky enough to land offers for tenure-track junior faculty positions find that starting salaries are not very negotiable.

High salaries at the top can attract productive workers, but low pay at the bottom signals that there may not be a good future in this career. If big rewards become concentrated among a smaller group of people in a highly competitive area, then others who could still have been productive scientists end up losing a disproportionate amount in terms of earnings and career prospects and it could keep promising people from further pursuing a research career. (Corie Lok, Nature)

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Written by sciencepolicyforall

September 27, 2016 at 11:47 am