On the importance of including pregnant women in clinical trials: A Q&A

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As a research scientist, I’ve negotiated the complex nature of getting approval to image human subjects. So I know firsthand that it is common to exclude pregnant women from clinical trials. Although this practice is well-intentioned, it is also misguided — according to an opinion piece recently published in JAMA. To learn more, I spoke with one of the authors, Heather Byers, MD, a clinical assistant professor in pediatrics at Stanford.

Why are pregnant women excluded from clinical trials?

“Historically, women in general were excluded from clinical trials because men were thought to be a more homogenous group without hormonal cycles and other sex-based variables that might impact the medical conditions under study.

In addition, pregnant women are still classified as a ‘vulnerable’ population for all research studies, so investigators must take additional steps to enroll them to ensure minimum risk.

Also, the lack of data about what pregnant women can safely be exposed to leads to more uncertainty. So many investigators choose to exclude them, even if they might benefit from the study intervention.”

Why is this a problem?

“Excluding them is a problem because women don’t stop getting sick or stop having chronic medical conditions just because they are pregnant. The average woman is exposed to four medications during her pregnancy and over 80 percent of medications haven’t been studied in a like population. This forces pregnant women to take medications on an “off-label” basis — meaning, the medications weren’t studied or approved for use in pregnant women — because there’s no other option. Pregnant women deserve better. It’s a matter of justice.”

What are the barriers and how can we overcome them?

“First, we advocate reclassifying pregnant women from ‘vulnerable’ to ‘scientifically complex.’ Pregnancy doesn’t alter a woman’s capacity for autonomous decision-making. Indeed, a pregnant woman frequently makes complex medical decisions for herself and her fetus that reflect her family’s values.

Another barrier for medical investigators is the perceived legal risk regarding a potential adverse outcome in the fetus or mother. As we discuss in the JAMA Viewpoint, this barrier could be addressed by standardizing the informed consent process.

Finally, federal regulations don’t define ‘acceptable risk’ to the woman or fetus and this uncertainty is perceived as a risk in itself. But in some cases, pregnant women may accept the uncertainty and risk.

For example, it was imperative to reduce mother-to-child transmission of HIV. So obstetricians reluctantly included pregnant women with HIV in their study of antiretroviral treatments, since the risk of the drugs were thought to be low and the potential benefit high. And the effectiveness of this study helped transform the AIDS epidemic.”

Is progress being made?

“Although progress has been slow, there has been an increased effort to enroll pregnant women. Several high-profile clinical trials involving pregnant women recently completed and institutions like the National Institutes of Health are working to change their polices. For example, the NIH Task Force on Research Specific to Pregnant Women and Lactating Women recently issued a report that summarizes the current gaps in knowledge and provides recommendations for continued progress.”

How did you become involved?

“I first became interested in this subject as a medical student during my rotation at NIH with Pamela Stratton, MD, one of the obstetricians involved in the study of antiretrovirals to prevent vertical transmission of HIV.

Later, as an obstetrics resident, I was frustrated by the lack of information to share with my patients regarding the risk and clinical impact of various medications, vaccines and medical conditions in pregnancy. Every anecdotal story  — such as my patient who was hospitalized in intensive care for months with influenza because she’d been too afraid to get the flu vaccine earlier in her pregnancy — is one too many. The fear of uncertain risk can be dangerous. There should be a better way.

One thing that has changed is the rise of social media and patient support group accessibility. Although this should not replace the controlled setting of a clinical trial, partnerships between motivated patient advocacy groups and medical investigators can be a powerful tool for obtaining information about risk and benefits going forward.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Cancer clinical trials: Stanford strives to enroll more diverse participants

Image by geralt,
Image by geralt

In a previous post, I described why I enrolled in a clinical trial at Stanford to treat my Hodgkin’s lymphoma. But I didn’t share the result: I received radiation therapy and chemotherapy — instead of the standard treatment of exploratory abdominal surgery — and I’m confident it helped me to be cancer free for the last 20 years.

However, my experience was unusual: Very few cancer patients participate in clinical trials and many aren’t even aware that they qualify for one. In order to advance cancer research, more participants are needed — especially ethnic and racial minorities who are vastly underrepresented in clinical trials. This is particularly important for diseases that occur more frequently or appear differently in non-white populations. For example, African American women have a 41 percent higher mortality rate for breast cancer than white woman, despite having a lower incidence rate, but only about 5 percent of clinical trial participants — for all diseases — are African American.

The Stanford Cancer Institute (SCI) knows this problem well.

“A key way participants learn about our cancer clinical trials is through physician referrals,” said Rachel Mesia, community engagement manager at SCI. “Physicians and oncologists practicing at Stanford educate their patients about clinical trials. They also network with physicians from other health-care practices to prompt them to make referrals.”

Participants also find Stanford cancer clinical trials through SCI’s clinical trials information service, which directs callers to an English- or Spanish-speaking outreach specialist who provides general clinical trials information and links callers to study coordinators.

Similarly, Mesia said SCI’s website and mobile app make it easier for patients to locate clinical trials that match their medical conditions using patient-friendly word searches. The mobile app will be updated in January to add new features.

“I’ve heard from many sick patients that they don’t have the energy to constantly go onto a search engine to see if any new clinical trials have opened up,” said Sarah Pelta, SCI’s communications manager. “That’s why were putting push notifications into our mobile app, as well as the ability to sign up for email notifications. So patients can just receive an email when a trial opens up that matches their search parameters.”

Also key to successful recruitment is the inclusion of stories from past clinical trial participants to help make a human connection. “From our website analytics and from speaking to patients, we know that patients really want to see what other patients are experiencing. So we’ve added patient photographs and videos to our website,” Pelta said.

SCI tackles the challenge of minority recruitment by reaching out to particular communities, in part by distributing information at community health and cancer patient events, Mesia said. “We also partner on educational presentations with a variety of community organizations, such as cancer support groups, social service organizations and churches,” she said. “And we participate in some ethnic-specific media interviews, including television, radio and newspapers.”

In addition, SCI has interactive kiosks dispersed throughout their cancer centers that provide basic clinical trials information and a search tool — in English, Spanish, Chinese and Russian.

Over the last six years, SCI has also held a Cancer Clinical Trials Awareness Week event to further increase visibility. In April 2017, this will be expanded to a month-long event highlighting genomics, immunology and other targeted approaches to cancer. Everyone is invited, and they’re planning to make the talks available online to expand access, Mesia told me.

The SCI has adequate participation overall, but they are still struggling to recruit minorities. “Currently our greatest disparity lies amongst the African American population,” Mesia said. “We’re doing okay with African Americans who are existing cancer patients at Stanford, but there is an issue when we look at our catchment area as a whole.” One barrier is that fewer African Americans live near Stanford’s cancer centers, and those living in more distant Bay Area counties have significant commute challenges, she said. “The reality is that some people’s personal lives make it unfeasible to be part of a Stanford clinical trial.”

But that just means the SCI staff need to work even harder. “We need social and health equity for all populations who are getting cancer,” Mesia said.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Cancer clinical trials: Why I chose to participate, but so many others don’t

Photo by geralt
Illustration by geralt

When I was 29 years old, I was one of the healthiest people I knew. I biked 10 miles to work, played ultimate frisbee, slept at least eight hours each night and ate nutritious, organic food. And then I found an enlarged lymph node in my neck.

My life suddenly became a whirlwind of doctor appointments and diagnostic tests: chest X-rays, blood tests, CT scans, a lumbar puncture, lymph node biopsy and a lymphangiogram. The tests showed another enlarged lymph node near my heart, and I was diagnosed with stage IIA Hodgkin’s lymphoma.

Unbelievably, I had cancer. I was faced with scary medical decisions that could impact both my survival and fertility. How do you make those kinds of decisions? As a scientist, I immediately started researching Hodgkin’s and talking to medical experts.

According to my physician, the standard treatment for stage II Hodgkin’s entailed exploratory abdominal surgery in order to biopsy my organs and check for further signs of the disease, as well as removal of my spleen. This would be followed by radiation therapy to my chest and neck.

Most people choose the standard treatment — it’s the gold standard for a reason, right? However, I wasn’t convinced that I wanted the surgery, because my diagnostic tests showed no sign of the disease below my diaphragm. I didn’t want to unnecessarily lose my spleen, which plays a vital role in the immune system by filtering blood and fighting certain deadly bacteria.

Luckily, my physician recommended another treatment option: a Hodgkin’s clinical trial at the Stanford Cancer Institute. This phase III clinical trial was testing whether a specialized chemotherapy cocktail was more effective at treating stage II Hodgkin’s than the standard abdominal surgery, and the investigators’ previous clinical trials had shown excellent results with similar chemotherapies.

So I struggled with whether I wanted radiation therapy combined with exploratory surgery or chemotherapy — both were scary and both would have long-term side effects. However, it wasn’t really my decision. I could only decide whether or not to enroll in Stanford’s clinical trial, and then the treatment option would be randomly selected for me. Eventually I decided I could live with this lack of control, because both treatments were going to be effective.

People typically participate in a clinical trial to “advance medicine” or “improve the lives of others,” according to the Center for Information and Study on Clinical Research Participation. While I was happy to contribute to scientific research, I enrolled in the clinical trial for myself — to get the best care. I knew that other study participants came from across the world to Stanford since it was one of the premier places for Hodgkin’s treatment, and I lived just five miles away.

I was fortunate in many other ways as well; I had personal health insurance. I also had flexible hours as a research scientist and could work full-time during treatment, so I didn’t have financial worries. In addition, I was used to communicating with doctors as peers, so I didn’t fear being a ‘guinea pig.’

These types of barriers — limited access to trials, financial concerns and trust issues — prevent many people from participating in clinical trials. Nationwide, only about 3 percent of adults with cancer participate in clinical trials. As a result, about 40 percent of all oncology clinical trials fail to meet their minimum patient enrollment, which has a major impact on cancer research.

Researchers use many tactics to attract trial participants. In an upcoming post, I’ll share what I learned about Stanford’s efforts to boost the enrollment of minorities in its oncology clinical trials.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.