By: Nivedita Sengupta, PhD
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)
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)
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)
Have an interesting science policy link? Share it in the comments!