http://www.sciencedirect.com/science/article/pii/S1359644611004417
Drug Discov Today. 2012 Feb;17(3-4):97-9. Epub 2011 Dec 22.
The routes to orphan drug designation - our recent experience at the FDA.
Lev D,
Thorat C,
Phillips I,
Thomas M,
Imoisili MA.
Center for Rare Disease Therapies, Keck Graduate Institute of Applied Life Sciences, Claremont, CA, United States.
Also of interest:
http://www.orpha.net/actor/EuropaNews/2012/120208.html#25810
The process of obtaining orphan drug designation in the USA
A recent article in Drug Discovery Today describes the route to orphan drug designation in the USA. Succinctly written, the authors provide an overview of the requirements and processes for successfully obtaining a designation. Using the designations issued in the year 2009 as an example, this article provides insight into the designation process and could be particularly helpful to companies preparing an application for an orphan product designation.
“Parents who frequently move house put children’s health at risk,” according to the Daily Mail. The newspaper said that research found moving several times can affect children’s health and psychological state, and also increases the likelihood that a child may use illegal drugs.
This Scottish research, which looked at potential links between moving house in childhood and adult health, produced far more mixed results than the Mail implied. However, the press release accompanying the research did not always clearly reflect the findings of the study, which found very few significant links between moving frequently and poor health.
In fact, once the researchers accounted for factors such as social deprivation and moving schools, moving house was only significantly linked to a higher chance of using drugs in later life. Adults who had moved frequently showed no greater risk of being overweight, having high blood pressure, long-term illness, psychological distress, drinking or smoking later in life.
While researchers say the risk of having certain measures of poor health was “elevated” in people who moved house more frequently as a child, the increase in risk was not statistically significant, which means it could have happened by chance.
Where did the story come from?
The study was carried out by researchers from the Medical Research Council, the University of Stirling, Queen’s University and Scotland’s Chief Scientist Office. It was funded by the Chief Scientist Office of the Scottish Government Health Directorate. The study was published in the peer-reviewed Journal of Epidemiology and Community Health.
The study’s findings were overstated by the Daily Mail. The newspaper reported that there were “negative health effects” from frequent moves, whereas the study found that frequent moving was only significantly linked to an increased chance of drug use. This finding on drug use was found to be independent of other variables.
Moving during childhood was not significantly associated with adult measures of physical health, such as weight and blood pressure. The Mail only touched on these elements towards the end of its report.
It’s worth noting that in the press release that accompanied publication of the study, it only the penultimate paragraph stated only illegal drug use was independently associated with frequent moves.
What kind of research was this?
This research was part of a large cohort study from the west of Scotland, which has taken place over 20 years. Its aim was to compare the health of people who had been “residentially stable” during childhood with those who had moved house, using a range of health measures.
The authors say previous research suggests that frequent childhood moves may be associated with poorer health outcomes and behaviour in adolescence. The researchers say their present study brings together a wider range of health outcomes than has previously been considered, and also looked at the extent to which associations between childhood mobility and health in adolescence last into adulthood.
What did the research involve?
The study was based on a cohort of 1,515 participants who were 15 when it started in 1987 and who were followed up for 20 years. Data from this cohort were collected at five points in time, the final time when the participants were 36. The final sample analysed in the study was 850 participants, so 665 original participants (44%) were not included in the final analysis because they had left the study.
Researchers collected their data through face-to-face interviews conducted by nurses. A parental questionnaire was completed at the start of the study.
The researchers got information about moving house from the number of addresses people had lived at between birth and 18 (they excluded recent moves out of the family home). They collected information on a range of health measures including:
- Physical health measures - these were all taken by nurses and included body mass index, waist-to-hip ratio, lung function and blood pressure.
- Overall health - people were asked to report whether they had limiting long-term illness (answering yes or no) and to give their own assessment of their general health, as rated on a four-point scale.
- Psychological distress - this was assessed using a standard 12-item questionnaire (with a cut-off score of 3 points taken to indicate psychological distress). Whether people had thought about suicide was also examined, with people asked at certain points whether they had thought about taking a drug overdose or deliberate self-injury. The third measure of psychological distress was anxiety, as measured on a standard scale.
- Health behaviours - the behaviours examined were heavy drinking (defined as exceeding maximum weekly safe limits), illegal drug use and smoking.
Importantly, the researchers also looked at participants’ family and household circumstances based on information provided by the children’s parents at the start. They also looked at other factors such as social deprivation (calculated by postcode and using recognised deprivation categories), housing status (home owner or not), social class, family structure (intact or not) and number of siblings. Also included were data on school mobility, derived from the number of primary and secondary schools attended. The researchers also looked at participants’ social class, education and marital status in adulthood.
The researchers then analysed the relationship between number of house moves in childhood and health at the ages of 18 and 36. They adjusted their findings for possible confounders, such as social class, deprivation and family circumstances.
What were the basic results?
The researchers found that approximately one in five people did not move address throughout childhood. Three in ten moved once or twice, and a further one in five had moved at least three times. They also found that children in single-parent households and those with two or three siblings were significantly more likely to have moved home (while those with at least four siblings were more likely to have stayed put).
After they adjusted their findings for both socioeconomic circumstances and the number of school moves, the researchers found that, when the participants were 18:
- People who had moved at least three times were significantly more likely to have used illegal drugs than those who had never moved (odds ration [OR] 2.44, 95% confidence interval [CI] 1.45 to 4.10).
- Those who moved at least once had a significantly higher chance of scoring 3 or more (indicating distress) on the questionnaire for psychological distress than those who had not moved at all (OR=1.62, 95% CI 1.11 to 2.35).
- The risk of several outcomes (having a long-term illness, having suicidal thoughts for those who had moved at least once, and heavy drinking and smoking for those who had moved at least three times) were “elevated” compared to those who had not moved at all, but the increased risks were not significant.
- There was no association between childhood mobility and physical health measures such as blood pressure and weight.
When the participants were aged 36, the researchers found that:
- Frequent moving in childhood was independently associated with illegal drug use (OR 1.92, 95% CI 1.00 to 3.69).
- The odds of poor health across other measures remained “elevated” but not statistically significant.
- There was no association between moving address during childhood and physical health measures such as blood pressure and weight.
How did the researchers interpret the results?
The researchers concluded that increased residential mobility in childhood is associated with an elevated risk of poor health in adulthood, across a range of measures. This is explained in part, they say, by both social and economic circumstances and the frequency of school moves.
The relationship between childhood residential mobility and poorer health appeared to be stronger in adolescence than adulthood, possibly because people’s own socioeconomic circumstances lessened the effects over time.
Conclusion
This study looked at the effect of multiple address moves during childhood on people’s physical and psychological health at the ages of 18 and 36.
The way the authors interpreted the results of their study is confusing. They say that a higher risk of poor health outcomes is associated with frequent moves of home in childhood. However, the only significantly higher risk, once the results were adjusted for various confounders, was illegal drug use. This is important because it means that the other increases in risk identified are more likely to have occurred by chance.
The study examined an important issue, and one strength is the length of time of it covered. Another is its detailed collection of data, which might help explain why frequent moves of house could have an association with poorer health outcomes. For example, this could be because of frequent school moves, family break-up and deprivation.
However, the study has a number of limitations. Its high drop-out rate (around 43%) raises the question of reliability and it is possible that those who dropped out or were lost to follow-up also had the most mobile childhoods. The study’s reliance on the parents to report outcomes, such as overall health, is another limitation as their reports may be subjective or difficult to appraise.
Families move home for a range of different reasons, including improved schooling and employment opportunities, change in financial circumstances or family break-up, and the study did not assess the reasons for the family moves. It seems obvious that children are more likely to be negatively affected when disruption or financial problems cause a family to move, rather than when the motive is to seek better schools or a better job.
The way children’s wellbeing is affected by frequent moving is an important issue, but it is also a complex one which needs to be examined further.
Links To The Headlines
Parents who frequently move house 'put children's health at risk'. Daily Mail, February 9 2012
Links To Science
Brown D, Benzeval M, Gayle V et al.
Childhood residential mobility and health in late adolescence and adulthood: findings from the West of Scotland Twenty-07 Study. Journal of Epidemiology and Community Health, Published Online First 6 February 2012
An endocrine hormone used in clinical trials as an anti-obesity and anti-diabetes drug causes significant and rapid bone loss in mice, raising concerns about its safe use, UT Southwestern Medical Center researchers have shown.
The hormone, fibroblast growth factor 21 (FGF21), promotes bone loss by enhancing the activity of a protein that stimulates fat cells but inhibits bone cells, researchers report in a study available online in Proceedings of the National Academy of Sciences.
"This hormone is a very potent regulator of bone mass," said Dr. Yihong Wan, assistant professor of pharmacology and senior author of the study. "When we oversupply FGF21 in mice, it results in substantial bone loss."
Though the political fight over GE salmon has primarily focused on the potential environmental impact of the technology--a fight fueled by environmental groups and lawmakers with constituent salmon interests--the petition, brought by Consumers Union, Food & Water Watch and the Center for Food Safety is focused primarily on food safety concerns.
Developed by Massachusetts-based AquaBounty Technologies, the engineered AquAdvantage Salmon are essentially Atlantic salmon with an inserted growth gene from a Chinook salmon and an antifreeze gene from an ocean pout. They grow twice as fast as typical Atlantic salmon and require approximately 10 percent less feed to achieve the same weight.
If cleared by FDA, the fish would be the first GE animal approved for human consumption.
"Atlantic salmon is a substance traditionally regarded as safe. [AquaBounty's] GE process significantly alters the salmon's composition, however, in a way that is reasonably expected to alter its nutritive value or concentration of constituents, and the new substance raises safety concerns," reads the petition. "Under the Agency's regulations and guidelines, such a substance must be treated as a food additive and the Agency must make a closer inquiry into the safety of its consumption, including, but not limited to, subjecting it to extensive pre-market testing."
The petition also asks that the agency not designate the GE salmon as generally recognized as safe (GRAS). As the petition notes, food additives are presumed to be unsafe, and therefore the company seeking approval for an additive "carries the burden to prove that a food additive is GRAS.
The groups blasted the data supplied by the company to FDA's Center for Veterinary Medicine and said it "cannot be relied upon to show that AquAdvantage salmon is safe to consume."
"The data FDA has on GE salmon, which were supplied by Aquabounty, are incomplete, biased, and cannot be relied upon to show that the GE salmon is safe to consume," said Food & Water Watch executive director Wenonah Hauter. "Aquabounty's own study showed that GE salmon may contain increased levels of IGF-1, a hormone that helps accelerate the growth of the transgenic fish and is linked to breast, colon, prostate, and lung cancer."
In the petition, consumer groups warn that the potential health risks of GE salmon are no "different from a number of food additives the FDA has banned in the past, including those that are cancer causing."
"FDA's choice to allow the first proposed transgenic animal for food to somehow only be review as a drug is contrary to law, science and common sense," said George Kimbrell, senior attorney for the Center for Food Safety. "Public health and transparency should be championed, not skirted, particularly when contemplating such an unprecedented approval."
Aquabounty did not respond to requests for comment on the petition.
The company maintains that the GE salmon are biologically and nutritionally identical to non-GE salmon and pose no threat to human health.
The
CDC study, published as
a letter Wednesday in the Journal of the American Medical Association, looked at trans fat levels in people before and after the
2006 Food and Drug Administration mandate requiring trans fat amounts to be listed on Nutrition Facts food labels.
Even before that rule was imposed, the prospect of FDA action and heightened publicity about the risk of heart disease from trans fat spurred a switch to healthier oils. The CDC study sought to determine the effect of government regulation and those other moves.
Christopher Portier, director of CDC?s National Center for Environmental Health said all the efforts were effective "in reducing blood TFAs (trans fatty acids) and highlight that further reductions in the levels of trans fats must remain an important public health goal."
"Credit for the reductions in trans fat is shared by many parties," noted a news release from Michael Jacobson of the Center for Science in the Public Interest. CSPI has petitioned the FDA over trans fat, and also sued restaurants chains that were frying foods in partially hydrogenated oil. "New York, Philadelphia, Baltimore, California, Montgomery County, MD, and other jurisdictions banned most artificial trans fat from restaurant food.
"The FDA helped greatly by requiring that trans fat be listed on Nutrition Facts labels. And oil processors, seed developers, and farmers worked hard to produce and market healthier oils for restaurants and food manufacturers to use," said Jacobson, adding that the dramatic drop in trans fat levels in people "represents enormous public health progress and is almost certainly preventing thousands of heart attacks and premature deaths each year."
CSPI says more must be done. In urging the FDA to ban partially hydrogenated oil -- a major source of trans fat -- it has
highlighted the foods still loaded with trans fat. It observes that the U.S. Department of Agriculture, which has jurisdiction over foods with meat or poultry such as pot pies, has not adopted the FDA's trans fat labeling rule.
Unlike other dietary fats, trans fats are not essential to human health and do not promote good health. High consumption of trans-fatty acids is linked to cardiovascular disease in part because TFAs increase LDL cholesterol ("bad" cholesterol), the CDC says. Changing to a diet low in TFAs may lower LDL cholesterol levels, thus decreasing the risk for cardiovascular disease.
To avoid trans fat in one's diet, the CDC recommends:
- Looking for the trans fat listing on the Nutrition Facts label. Comparing brands and choosing the one lowest in trans fat, preferably with no trans fat. - Replacing margarine containing trans fat with unsaturated vegetable oil. - If you use margarine, choose a soft margarine spread instead of stick margarine. Check your labels to be sure the soft margarine does contain less trans fat. If possible, find one that says zero grams of trans fat.
While the current study looked only at white adults, CDC researchers are also looking at blood TFAs in other adult race/ethnic groups, children and adolescents, Portier said. The trans fat research is a part of a larger
National Biomonitoring program, which measures more than 450 environmental chemicals and nutritional indicators in people.
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