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Lately, we’ve been inundated with information on women’s underrepresentation in the fields of science, technology, engineering, and mathematics (STEM). But what doesn’t get a lot of recognition is that inequality in science doesn’t just apply to the gender of the people working on new developments–it can extend to the nature of the developments themselves. Medical research has a history of being disproportionately biased toward men, despite the fact that differences between the sexes affect everything from how diseases should be treated to how medications are developed. Bias in medical research extends beyond the lab, and that’s a problem. Read on to learn about the need for equality in medical research, and how ensuring that equality is a step toward good health for all.

History of Sexism in Science

Sexism has been endemic in many aspects of scientific research; a full historical review would be as lengthy as it would be disheartening. But it’s important to recognize a consistent tradition of sex-based inequality in medical research. It has long been assumed that conclusions can be applied generally to both men and women, without taking into account the need to design studies that focus specifically on the biological and physical differences between the sexes. There have been myriad reasons for this lack of female inclusion. Science was heavily focused on studying the “norm,” and the “norm” as pertaining to scientific research was a roughly 155-pound man. Moreover, it was believed that the only difference between men and women were their respective sex organs. Furthermore, concerns regarding testing on pregnant women, or potentially-pregnant women, and the harm that could happen to fetuses discouraged researchers from including women of child-bearing age, and sometimes women as a whole due to their changing hormone cycles.

However, those assumptions finally began to change, albeit slowly, in the later decades of the 20th century. In 1985, a report released by the Public Health Service Task Force on Women’s Health Issues concluded that “the historical lack of research focus on women’s health concerns has compromised the quality of health information available to women as well as the health care they receive.” Founder of the Society for Women’s Health Research (SWHR ®) Dr. Florence Haseltine, MD, PhD, was working for the National Institutes of Health (NIH) in the mid-1980s when she began championing the need for medical research that recognized differences between men and women. She eventually coined the term “sex-based biology,” essentially meaning the study of the sex differences between men and women and how they apply to different aspects of medical research and health. Dr. Haseltine worked to confront different ways in which this inequality was manifested, including by advocating for more women to be included in clinical trials. Despite the fact that the NIH had recognized that inclusion of women in clinical trials is essential, they still aren’t always included.

These revelations sparked action by government agencies including the NIH, the Food and Drug Administration (FDA), and the Congressional Caucus on Women’s Issues. But it correspondingly also sparked the need for an organization that could champion the cause of sex-based biology head on. The Society for Women’s Health Research (SWHR) was founded in 1990 to “bring attention to the lack of inclusion of women and minorities in medical research and clinical trials.”

While progress has been made in including women in scientific research, there’s still substantial work to be done. Women and minorities remain underrepresented in clinical trials and medical research.

Why is it so important that sex differences are taken into account in medical research?

Put simply: men and women are biologically different. Health differences between men and women range from a prevalence of a particular disease, to the ways in which it manifests itself, to the drugs used to treat it. For example, SWHR focuses on Alzheimer’s Disease and Cardiovascular Disease (CVD) as two of the many illnesses that deserve a look through a sex-based biological lens.

Alzheimer’s Disease 

Alzheimer’s Disease is one example of a condition that disproportionately affects women. In fact, women are almost twice as likely to be affected by Alzheimer’s as men. Overall, it is the fifth most common cause of death for American women. This increased prevalence for women isn’t just coincidental. There are specific sex differences that need to be taken into account when it comes to the study of how and why Alzheimer’s Disease strikes some and not others. According to experts at SWHR’s Alzheimer’s Roundtable, there are many different factors to consider:

Women suffering from depression have a 90 percent increased risk compared to men and an even greater risk after menopause, due to decreased estrogen levels. Another risk factor is having a hysterectomy and ovaries removed. Women who remove their ovaries before the age of 48 have a 70 percent increased risk of developing Alzheimer’s. However, if that woman used estrogen hormone therapy until menopause, she reduces her risk.

In order to prevent the devastating onset of Alzheimer’s–which is estimated to affect 15 million people over the next 15 years–it is essential to understand what role sex differences play and how women’s physiology can make them, in some cases, more susceptible.

Cardiovascular Disease (CVD)

Despite popular perception about its frequency in the male population, cardiovascular disease (CVD) remains an acute problem for women. In fact, CVD accounts for one in three deaths among American women–more than all cancers combined.

It’s also another example of an illness that can manifest differently between men and women, and has different risk factors. For example, CVD appears on average seven to 10 years later for women than men. There are also risk factors that are more visible for women than men, such as the fact that young women who smoke are at a higher relative risk for developing CVD than men who smoke.

Moreover, the way that CVD presents in women can be different than in men–sometimes leading to a failure by healthcare professionals to detect symptoms in a timely fashion. Women’s symptoms can include fatigue and indigestion, and can appear up to a month before a heart attack. These differences can also lead to misdiagnosis when a woman is actually experiencing a cardiac event–a study in The New England Journal of Medicine found that women under 55 were seven times more likely to be misdiagnosed than men. It’s important that researchers and doctors consider how not only different sex-based risk factors contribute to CVD, but also how different symptoms present themselves.

Another issue with a male-centric view of CVD is that symptoms that are more prevalent for men have been more widely publicized and focused upon in public service campaigns. As a result, women may not recognize the symptoms or risk factors themselves–the following video created by SWHR highlights some of the gaps in public knowledge:

Continued Underrepresentation in Clinical Trials and Research

It’s evident that progress has been made in including women in clinical trials–particularly when it comes to specific topics like heart disease and breast cancer. However, there’s still much work to be done. As recently as 2014, the FDA moved toward greater transparency in disclosing the sex breakdown of those who participate in clinical trials. However, that news was bittersweet–it confirmed long-standing concerns about the inclusion of women in clinical trials. SWHR released a statement about the FDA’s disclosure, stating:

We commend the FDA for the effort in collecting and releasing these data to the public and we believe it is an initial first step towards reducing the disparities and lack of information on sex and ethnic differences. But as is evident, the percentage of minority participation is dismal and while there are women in all of the trials, the numbers are not statistically significant to reach any clinical relevance.

So, where are researchers still struggling when it comes to including women in clinical trials and research?

Cardiovascular Disease Clinical Trials 

While the risk of CVD has been well-recognized by proponents of sex-based biology, and women have been increasingly included in studies about cardiovascular disease, there’s still a struggle to make sure that studies report on gender differences. According to a 2009 paper by the American Heart Association (AHA) on the “Status of Women in Cardiovascular Clinical Trials,” both government and non-government studies continued to fail to report on sex differences in CVD studies between 2000-2006. The AHA stated:

An analysis of trials included in Cochrane meta-analyses (Cochrane Systematic Reviews) for the inclusion of women in cardiovascular clinical trials and for the reporting of gender-based analyses showed similar results. Of 258 clinical trials studied, women constituted only 27 percent of the pooled population and of 196 trials which included both genders, only 33 percent reported gender-based outcomes. When analyzed by year of publication before or after 1993, there was no difference in the frequency of gender-based analyses.

In order to ensure that the differences in the ways that women and men present and experience CVD are taken into account, reporting on sex differences in clinical trials needs to be a priority.

Conclusion

There’s no doubt that we’ve come far in this field and an improved concentration on exploring sex-based biology has resulted in a better understanding of sex differences–but we need to continue to such efforts in order to promote good health for all men and women. Clinical trials need to be designed to ensure not only the inclusion of, but also the recognition of their differences. Working toward inclusivity of medical research will benefit us all by increasing our understanding of what causes various illnesses and how to treat them.

Resources

Primary 

Society for Women’s Health Research: History

Society for Women’s Health Research: Timeline

Society for Women’s Health Research: News

U.S. Department of Health and Human Services: Leading Causes of Death

Additional

Journal of Applied Physiology: Sex and Gender: What is the Difference?

American Heart Association: Status of Women in Cardiovascular Clinical Trials

Chronic Neuroimmune Diseases: Yes, Biologically Speaking, Sex Does Matter

American Journal of Nursing: Progress, Not Perfection

Newswise: Alzheimer’s and the Downward Spiral: SWHR Holds Congressional Briefing About Women and Alzheimer’s Disease

Netherlands Heart Journal: Gender Differences in Coronary Heart Disease

Heart Sisters: Heart Attack Misdiagnosis in Women

Society for Women’s Health Research

The Society for Women’s Health Research (SWHR®), is a national non-profit based in Washington D.C. that is widely recognized as the thought-leader in promoting research on biological differences in disease. SWHR is dedicated to transforming women’s health through science, advocacy, and education. Founded in 1990 by a group of physicians, medical researchers and health advocates, SWHR aims to bring attention to the variety of diseases and conditions that disproportionately or predominately affect women. For more information, please visit www.swhr.org. Follow us on Twitter at @SWHR. SWHR is a partner of Law Street Creative. The opinions expressed in this author’s articles do not necessarily reflect the views of Law Street.

The post Sexism in Science: Bias Beyond the Lab appeared first on Law Street.

The recent Ebola outbreak is plaguing thousands across West Africa with illness and even death. In the modern age of science, it seems incomprehensible that there is not yet a vaccine for Ebola. Though the virus is an urgent health concern, pharmaceutical companies have few incentives to develop drugs to combat the disease. Read on to learn what happens when economic incentives do not align with public health needs, and what better solutions may exist for drug development.

What is the status of the Ebola outbreak and vaccine?

Ebola virus disease is characterized by fever, intense weakness, and muscle pain, leading to more severe symptoms. Ebola was initially transmitted by animals and is now spreading between humans through contact with bodily fluids. The outbreak was first detected in Guinea, by which time it had already spread to Liberia, Sierra Leone, Senegal, and Nigeria. A separate outbreak occurred in the Democratic Republic of Congo, which is believed to be unrelated to the outbreak in West Africa. The virus has primarily infected villages where there is extreme poverty and insufficient medical care to combat the spread of the virus.

Statistics

Mortality rates for the Ebola virus are well over 50 percent. Since March, Ebola has killed more than 1,500 people, making it the deadliest outbreak of the virus in human history. The World Health Organization estimates that the Ebola outbreak could affect 20,000 within the next nine months, and that roughly half a billion dollars is needed to stop the spread. Watch the video below for more information on the outbreak:

Vaccines

Ebola first appeared in 1976, yet nearly 40 years later no approved vaccination exists. In part this is due to the nature of the virus. Since incidents of Ebola are rare and occur in remote villages, it is difficult for scientists to effectively obtain samples and study the disease. Scientists cannot predict when an Ebola outbreak will occur, and even during a typical outbreak there are rarely enough people for a vaccine trial.

Since the outbreak, scientists are furiously working on an Ebola vaccine, and requests for approval are being fast-tracked. In the United States, the National Institutes of Health partnered with GlaxoSmithKline to develop a vaccine. The potential vaccine tested very well on primates, but the trial on humans only began on September 1. Initial data from the trial will not be available until late 2014. A number of other prototype vaccines are being worked on across the world.

Other Treatments

ZMapp was the experimental drug given to two Americans who contracted Ebola this year. While vaccines are designed to prevent future infections, ZMapp was designed to treat an existing Ebola infection. Both Americans who took the drug recovered, but the company that manufactured ZMapp has exhausted its supply.

What is the drug development process like?

Developing a new drug or vaccine is an extremely long process due to stringent regulation. Candidates for a new drug to treat a disease range anywhere from 5,000 to 10,000 chemical compounds. Of these compounds, roughly 250 will show promise enough to warrant further tests on mice or other animals. On average, ten of these will then qualify for tests on humans. Since certain outbreaks, such as Ebola, do not lend themselves to have vaccines ethically tested on humans, the United States does provide a way for the drugs to be approved on animal tests alone.

Pre-clinical and clinical development for a new drug takes between 12 to 15 years, though the Ebola vaccine should come much sooner. Pre-clinical development includes testing the various chemical entities and meeting all regulations for use. Three sets of clinical trials are then conducted on humans. Clinical phases include trials on healthy humans to test for the safety of the drug. Testing then moves to those who are ill to see if the treatment is successful. If successful, the drug is submitted for further approval by the Food and Drug Administration. Other countries have similar regulatory bodies to the FDA. Internationally, the World Health Organization oversees which drugs can be used to combat a crisis like Ebola. Learn more details about the development process by watching the video below:

The problem is not that scientists lack the capability to create an Ebola vaccine, but rather that the economics of drug development do not entice companies to develop such a vaccine. Pharmaceutical companies estimate the cost of the entire process of developing a new drug to range from hundreds of millions to billions of dollars. Many times the drugs are not successful, in which case the companies have spent a huge amount of money and have no profit-making product. A Forbes analysis estimates that 95 percent of experimental drugs tested ultimately fail. Only one in five that reach the clinical trial phase are approved.

Given the low rate of success for potential drugs and the huge amounts of money that can be spent on research and development of drugs, cost plays a huge factor. In the United States, basic discovery research is funded primarily by government and philanthropic organizations. Development in later stages is funded mostly by pharmaceutical companies or venture capitalists.

Why do some see funding as a problem?

Funding for areas that support public health is a tricky issue. Since pharmaceutical companies are looking to make a profit, they have an incentive to make drugs that a large number of people will take and be on for a long time. Most research and development for these companies target diseases that affect wealthy people in primarily Western countries.

Targeting wealthier clients leads to a severe underinvestment in certain kinds of drugs. Diseases of poverty cannot compete for investment from financial companies looking for big return. Ebola infects relatively few and primarily affects the poor. Ebola is similar to diseases like malaria and tuberculosis, which kill two million people each year but still receive little attention from pharmaceutical companies. Watch the video below for more on the economics of drug development:

Neglected Tropical Diseases, a set of 17 diseases including Dengue Fever and Chagas Disease, affect more than one billion people each year and kill half a million. Most of these diseases could be completely eradicated, but the drugs are not widely available. One study found that of the more than 1,500 drugs that came to market between 1975 and 2004, only ten were aimed at these diseases.

Even though developing countries may experience an outbreak of a disease, the demand for new drugs is limited. In rural villages in Africa, many reject clinical drugs for diseases such as Malaria and Tuberculosis. Instead, they favor spiritual healers and herbal remedies.

What is being done to promote drug research of neglected diseases?

The Office of Orphan Products Development (OOPD) in the FDA was designed to advance development of products that could be used to diagnose or treat rare diseases affecting fewer than 200,000 people. Orphan diseases do not traditionally receive much attention from pharmaceutical companies. The program provides a tax credit of up to 50 percent for research and development of drugs for rare diseases. When these drugs do become available, however, there is still no guarantee that patients will be able to afford them.

Since 1983 the OOPD program successfully enabled the development and marketing of more than 400 drugs and products. In the ten years prior, only ten of these products came to the market. Learn more about the OOPD with the video below:

Additionally, in 2007 the FDA created a voucher program to encourage research for neglected diseases. If a company receives approval for a drug for neglected diseases, it will receive a priority review voucher to speed up the review time for another application. Only four of these vouchers have been awarded so far.

Are there better ways to fund drug research?

Some argue that researching very rare diseases is not worth the time, and that instead research should be focused on more prevalent diseases. Companies will naturally invest in research for the most pressing concerns that offer the greatest opportunity for profit. Drug development for rare diseases should not be encouraged since the diseases occur so infrequently. Others argue research for rare diseases is essential to public health. The case of Ebola shows that even rare diseases can have a disastrous world impact.

Bioterrorism

Beyond public health, knowledge about the workings of any serious virus or disease is important to combat threats of bioterrorism. Concerns of bioterrorism are what led to Ebola research in the past. Serious threats of bioterrorism force the government to partner with research institutions to learn more about rare diseases. In March, the University of Texas and three other organizations received $26 million from the National Institutes of Health to find a cure for Ebola and the Marburg virus in case they were ever used for a bioterrorist attack. Other groups partnered with the Department of Defense to find an injectable drug treatment for Ebola.

Prizes

Prizes and grants are seen as ways to incentivize companies to develop drugs for diseases they might otherwise ignore. Financial incentives would encourage speedy development for an Ebola vaccine. The World Health Organization has looked into building a prize fund, where a centralized fund would reward drug manufacturers for reaching certain research goals. These tactics are more cost effective for the government, since they only have to pay if the product actually works. By creating grants for specific drugs, the government can pull research into neglected areas. Most prizes and grants, however, are not offered until a severe outbreak occurs, by which time many people are already in need of drugs.

Partnerships

Others point to room for greater partnerships between various entities for drug development. The greatest area for partnerships is between development groups and pharmaceutical companies. For instance, if a company pays to research and develop a product, the government could pay the company for the right to the product and could then promote the product itself without worrying about profit. In another case, GlaxoSmithKline and Save the Children arranged for someone from the charity to be on GSK’s research and development board, so the groups can share expertise and resources.

The Ebola outbreak indicates areas in which our current drug development model is lacking. People are dying because no Ebola vaccine exists. When pharmaceutical companies search only for profits, drugs for rare diseases go neglected. By expanding partnerships and offering greater prizes and financial incentives, the government can encourage drug research for these otherwise neglected diseases.

Resources

Primary

WHO: Ebola Virus Disease

FDA: Developing Products for Rare Diseases

CDC: Experimental Treatments and Vaccines for Ebola

Additional 

CNN: Ebola Outbreak: Is it Time to Test Experimental Vaccines?

Vector: De-risking Drug Development

Guardian: Funding Drug Development for Diseases of Poverty

Reuters: Scant Funds, Rare Outbreaks Leave Ebola Drug Pipeline Slim

Explorable: Research Grant Funding

Vox: We Have the Science to Build an Ebola Vaccine

American Society for Microbiology: Ebola Virus Pathogenesis

NBC: No Market: Scientists Struggle to Make Ebola Vaccines

Wall Street Journal: Two Start-Ups Aim to Change Economics of Vaccine Production

NPR: Would a Prize Help Speed Up Development of Ebola Treatments?

Harvard Global Health Review: Funding Orphan Drugs

LA Times: U.S. Speeds Up Human Clinical Trials

Washington Post: Why the Drug Industry Hasn’t Come Up with an Ebola Cure

New Yorker: Ebolanomics

Alexandra Stembaugh

Alexandra Stembaugh graduated from the University of Notre Dame studying Economics and English. She plans to go on to law school in the future. Her interests include economic policy, criminal justice, and political dramas. Contact Alexandra at staff@LawStreetMedia.com.

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