With all the talk about personalized medicine, one would think that clinical drug trials would address the differences between the sexes. Unfortunately, that’s not always the case.
Before a drug is introduced to the U.S. market, it will have gone through extensive human testing to ensure that it is effective, adheres to claims made by its maker, and is safe.
As a reporter, I covered the Federal Drug Administration for MedShadow, an online nonprofit that educates the public about the side effects of medicine (often not discovered before being approved for the public).
I was surprised and somewhat disenchanted to learn the following four things about the drug trial process that affect women and children.
#1: Men and Women Aren’t Equal
Isn’t it logical that a drug designed to be taken by both men and women should include trials that enroll a representative sample of female participants? But this doesn't always happen.
Women and children haven’t always been represented in the clinical trials that led to the approval of the drugs they are prescribed, especially for drugs prescribed off-label.
Off-label means that, once a drug is approved, licensed physicians may prescribe it for a condition, or for a patient, not indicated on the label — meaning that it hasn’t been FDA-tested for that particular condition or group of patients.
#2: The FDA Doesn't Always Study How Women’s Bodies React to Drugs
In 1977, the FDA issued guidelines recommending that pregnant women and women who could become pregnant should be excluded from large-scale clinical trials, such as Phase III studies.
Ironically, that guideline was a response to the diethylstilbestrol (DES) tragedy, where an unproven drug was given to millions of pregnant women from the 1950s to the 1970s.
It caused cancer and infertility issues in the children, and we are discovering that the grandchildren are affected too. (For more information on that, go to DESAction.org
That tragedy should have stimulated more equality.
In The University of Michigan Medical School’s news release, study author Reshma Jagsi, M.D., D.Phil., assistant professor of radiation oncology at the U-M Medical School said, “We know there are biological differences between the sexes, as well as social and cultural differences. Studies need to be able to assess whether there are differences in responses to treatment, for example, between women and men.”
#3: The FDA Doesn't Always Adjust Doses and Treatments Accordingly
Ambien is now the only drug on the market for which the FDA recommends different dosages for men and women. In 2013, the FDA cut the recommended dose of the sleep-inducing drug in half for women.
The agency did so after they found that women were metabolizing the drug in a way that caused higher levels to remain in their bloodstream than in men.
Women who took the same dose as men were at risk of waking up the next day and being unknowingly impaired when performing certain activities, such as driving.
After such research, why does the FDA apparently still think that women’s metabolisms are the same as men’s?
#4: The FDA Doesn't Always Protect the Youngest Rx Users
Children were rarely included in studies of medical treatments until about a decade ago, according to the FDA. Much is still unknown about how kids respond to drugs, biologics (including gene therapies) and medical devices.
Even when the adult dose is adjusted to the weight of a child, there is a chance that the dose used could be ineffective or even harmful, according to the NIH.
In addition, devices and drugs tested on adults may not be the proper size for a child’s size or metabolism, so research in children can lead to the development of chewables, liquids, or tablets that are easier for them to swallow and ingest safely.
“We had the peculiar situation of demanding a very high level of proof before a product was marketed for adults, but then having it used ‘off-label’ in children,” says Dianne Murphy, MD, director of the Office of Pediatric Therapeutics at the FDA.
But only 20 to 30 percent of drugs approved by the FDA have been labeled for use in children. That means physicians must use educated guesswork to determine correct dosages, while the actual side effects often remain unknown, Murphy added.
One of the more disturbing side effects of prescription drugs used for children surfaced around the class of antidepressants called SSRIs, which resulted in suicidal thoughts for some. Now these drugs carry a black box warning, noting an increased risk of suicidal thoughts and behavior in children, adolescents and young adults.
According to the FDA’s Pediatric Bioethicist Robert Nelson, MD, MDiv, PhD, “a child grows and the metabolism changes as he or she gets older. These changes mean the child has a different susceptibility to side effects over time. We may think we can predict some of these differences, but we really can’t without studying them.”
As a result, the FDA now encourages enrollment of children in clinical trials. Congress enacted two laws that will increase the study of drugs in children:
The Best Pharmaceuticals for Children Act (BPCA) provides an incentive for drug companies to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity.
The Pediatric Research Equity Act (PREA) requires drug companies to study their products in children under certain circumstances.
Before BPCA and PREA became law, more than 80 percent of the drugs approved for adult use were being used in children, even though their safety and effectiveness had not been established in children. Today that number has been reduced to about 50 percent, according to the FDA’s website.
I do indeed hope that FDA officials will soon reevaluate and revise the way they approach clinical drug trials for women. Doctors should not have to speculate what side effects and long-term effects treatments will cause for women, who clearly experience many of the same illnesses as men.
The current practice is not only illogical, but is one that puts women and children at risk, and also limits the scope of our knowledge of how medication works in every segment of the population.
Sarah Smedley writes the FDA Watch column for MedShadow. She has 20 years experience in communications for the medical, pharmaceutical, biotech, consumer health, fitness, philanthropy and nutrition industries.
Sources:
Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies: Volume I.
http://www.ncbi.nlm.nih.gov/books/NBK236532
Women under-represented in cancer research, U-M study finds. Health System University of Michigan. JUNE 08, 2009.
http://www.uofmhealth.org/news/1175women-underrepresented-in-cancer-rese...
FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR.
http://www.fda.gov/Drugs/DrugSafety/ucm352085.htm
Should Your Child Be in a Clinical Trial?
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048699.htm
Why Do Research In Children?
http://www.nhlbi.nih.gov/childrenandclinicalstudies/whydo.php
Antidepressant Use in Children, Adolescents, and Adults
http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/UCM096273
Should Your Child Be in a Clinical Trial?
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048699.htm
FDA takes step to encourage pediatric drug studies.
http://blogs.fda.gov/fdavoice/index.php/tag/pediatric-research-equity-ac...
FDA takes step to encourage pediatric drug studies.
http://blogs.fda.gov/fdavoice/index.php/tag/pediatric-research-equity-ac...
Reviewed November 20, 2015
by Michele Blacksberg RN
Edited by Jody Smith