Male bias in medical research and how it is hopefully changing! explained by Peter Rogers @ConversationUK

Equal but not the same: a male bias reigns in medical research

By Peter Rogers, University of Melbourne

Despite significant gains in gender equity over the last few decades, a bias still reigns in one area of medicine. The lack of female representation in both preclinical studies and clinical trials has put women at greater risk of adverse events from medical interventions. But there’s now light at the end of the tunnel.

Treating women equally as subjects in scientific studies may seem obvious today, when we have evidence of varied disease susceptibility and severity among the sexes. And of differences in men’s and women’s response to drugs and treatment outcomes. But this has not always been so.

So much variation

Differences between the sexes, or sexual dimorphism, is a key evolutionary adaptation in most species. It has existed in human life expectancy in almost every country for as long as records have been kept: women still live longer, on average, than men. Perhaps that’s partly because suicide rates are three times higher in men than women.

It’s not really surprising that after millions of years of evolution, fundamental differences exist in many aspects of our biology. Differences between the sexes have been documented in cardiovascular disease and stroke, chronic fatigue syndrome, asthma and several types of cancer.

Biological differences between the sexes include variation in genetic and physiological factors such as telomere attrition, mitochondrial inheritance, hormonal and cellular responses to stress, and immune function, among other things. These factors may account for at least a part of the female advantage in human life expectancy.

Research has highlighted gender differences in autoimmune diseases, such as rheumatoid arthritis, lupus and multiple sclerosis, and psychological disorders such as bipolar disorder, schizophrenia, autism spectrum disorder (ASD), eating disorders and attention deficit hyperactivity disorder (ADHD).

Rheumatoid arthritis, for instance, is approximately twice as common in females as in males. And a study found that while the relative risk of schizophrenia was greater in men up to 39 years of age, it reversed to a greater risk in women over the age of 50.

But why?

The reasons for these gender differences are varied and complex. Behavioural and social issues, such as uptake of smoking and body image, are different between men and women. This may partially explain differences in diseases such as lung cancer and eating disorders.

Normal physiological differences, such as a lower red blood cell count, may lie behind the poorer stroke outcomes in women. Women also tend, though, to suffer from stroke at an older age, which may account for some of the observed differences.

Biological differences also exist within the dopaminergic neurons of the brain and may explain varied prevalence of a number of neurological conditions. Indeed, fundamental genetic differences between the sexes may contribute to males under 20 years of age experiencing higher mortality rates from a wide array of conditions in 17 of 19 major disease categories.

What’s more, men and women differ in their response to drug treatment. Women experience a higher incidence of adverse drug reactions than men, although the reasons for this are not well understood. But we do know female response to many commonly used pharmaceutical agents can be different to males.

And we know the differences in drug responses are partly due to differences in body weight, height, body surface area, body composition, total body water, drug metabolism and drug clearance. Adult males have greater arm muscle mass, larger and stronger bones and reduced limb fat, but a similar degree of central abdominal fat.

Sex differences in body composition are primarily attributable to the actions of sex steroid hormones, which drive gender differences during pubertal development. Oestrogen, for instance, is important not only in body fat distribution but also in the female pattern of bone development, which predisposes women to a greater risk of osteoporosis in old age.

Does it really matter?

For the last two decades, the largest US funder of grants for biomedical research, the National Institutes of Health (NIH), has required studies involving human subjects to test both men and women. But Australia’s NIH equivalent, the National Health and Medical Research Council (NHMRC) currently has no comparable policy.

Medical research in Australia is substantially funded by the taxpayer, with the unambiguous goal of improving health for all citizens. From this viewpoint, there may be a need for policy reflecting that of the NIH’s here.

But the picture changes substantially in light of recent advances in medical science. Current thinking revolves around concepts such as “precision medicine”, which recognises that variability exists not just between the sexes, but between individuals.

So, the goal now is to ensure that every patient receives the correct treatment and dose at the right time, with minimum adverse side effects. Women may have been neglected by medical research for a couple of decades but the march of technology is now bound to take them forward as individuals.

The Conversation

This article was originally published on The Conversation.
Read the original article.

Awesome @ACSReactions infographic explains why there is no cure for #Ebola yet – hint – research, money, time

on Imgur here.

Does less money encourage scientists to cut corners?? Richard Harris reports for @NPR

harrisnpr

We at CauseScience have certainly been WOWed by the terrific reporting by Richard Harris and NPR on current issues in biomedical science over the last week! However, the article above on NPR from Richard Harris seems considerably less supportive of scientists. The article points out some very real issues that have arisen due to funding cuts in terms of patients involved in clinical trials. However, to me, the article also insinuates that funding cuts have made scientists lose their scientific integrity (cash-strapped scientists cut corners).

There’s a funding crunch for biomedical research in the United States — and it’s not just causing pain for scientists and universities. It’s also creating incentives for researchers to cut corners — and that’s affecting people who are seriously ill.

Take, for example, the futile search for drugs to treat ALS, better known as Lou Gehrig’s disease. The progressive, degenerative disease of the brain and nerve cells has been the focus of recent publicity, thanks to the Ice Bucket Challenge.

Harris is 100% correct on the negative impact of the funding cuts over the last decade that hurt researchers, universities, and patients (as he has examined in many of his other great articles). Most researchers are strapped for cash AND time, and have had to spend more and more time trying to get cash. Therefore, scientists cannot do all of the experiments they would like to, and so experiments get prioritized. This means that in some studies, crucial experiments (or replication/validation) can’t be performed to the highest standard due to lack of time and money and other resources.

But… there is a big difference between scientists not having time and money to correctly execute experiments, and scientists ‘cutting corners’ and overselling results to get ahead. The vast majority of scientists want to perform high quality research that will benefit patients. Harris correctly points out that replication is an issue in ALS research, as well as in ALL fields of biomedical research (see CauseScience posts about retractions, fraud, and research misconduct). And while it is true that as funding becomes harder to get, scientists are under more pressure to sell their science, the proportion of scientists committing actual fraud, misconduct, and retracting papers, is a tiny minority (that is starting to be addressed). And as far as careers where there is true fraud going on, society is detrimentally affected much more by many others compared with scientists (ahem: politicians, wall street, etc).

The emphasis of the article should be that patients become vulnerable when scientists do not have ADEQUATE funding. Emphasis on funding, not on scientists cutting corners.

Additionally, in my biased opinion, Harris’ use of ALS research is a terrible example. If only because the ‘futile search for drugs to treat ALS’ predates any current or past crunch on biomedical funding.

Most of the experimental ALS drugs, it turns out, undergo very perfunctory testing in animals before moving into human tests — based on flimsy evidence.

Recent funding cuts have little to do with the ‘very perfunctory testing in animals before moving into human tests’ when it comes to ALS research and ALS clinical trials. Until the recent explosion in genetic and molecular findings in ALS, very little was known about ALS, and clinical research was based on a relatively poor mouse model representing only a small fraction of ALS cases. The amount and stringency of drug testing done in this model before moving into humans has not undergone dramatic changes with funding cuts. While this may seem like ‘bad’ research, it was a whole lot better than no research. Especially when you consider the extremely short survival time of ALS patients, which creates a constant ‘race’ to find a cure. Case in point, the Ebola treatments and vaccines that were recently fast-tracked by the NIH and FDA with rather limited preliminary data. This isn’t an ideal way to perform science, but should it be considered cutting corners?

Harris notes the only positive aspect of these failures to translate treatments into patients, and that is increased stringency in taking drugs to humans.

Landis has since added new guidelines that scientists must follow before the neurology institute will fund large drug tests on people.

“There are now clinical trials that would have been funded five to seven years ago which won’t be funded until the preclinical studies are done in a way that is actually believable,” she says.

In principle, this should help scientists focus on more promising therapies.

It is great that NIH and NINDS are emphasizing solid preliminary research before moving into human trials. It would be great to see potential drugs validated using the best experimental designs and replicated by multiple groups, but that requires a financial commitment that has not always been available.

Most scientists do not want to cut corners, do not want to negatively impact patients, and certainly do not expect glory or fame. The vast majority of scientists want to learn something new and help people and society. Lastly, there is not only a desperate need for scientists to communicate and sell their research for their own funding, but even more importantly to generate public and political support for science funding. Harris’ inclusion of ALS, which is not the best example, but definitely a trending and popular one, demonstrates the ease with which we slip into trying to sell a good story. Scientists and writers beware.