Read Between the Lines: Understanding Clinical Studies

When Courtney Teicher received a diagnosis of thyroid cancer in 2011, she wasn’t sure which was preferable: surgery to remove the thyroid gland or radioactive iodine treatment. She started reading about what the thyroid does and the benefits of keeping the gland versus removing it, given her early-stage diag­nosis. That led Teicher, from Scotch Plains, New Jersey, to examine the pros and cons of taking the brand-name versus generic hormone treatment after surgery. She started her research with general websites, then moved on to case studies comparing experiences of people taking the medications. Eventually, she read clinical trial results.

Teicher once worked in an emergency department and has a degree in child development, but she does not have a formal medical education. “Not knowing what all of it meant, I’d look at the beginning, to see what the study was about, and the end,” she says. She also noted the medication’s side effects.

^{Courtney Teicher read study results to help her decide how to treat her thyroid cancer.}

Brandi Forbes of Cincinnati started looking at medical studies about the time she had a risk-reducing bilateral mastectomy in 2009, at age 23. Although she did not have breast cancer, she does have a BRCA gene mutation, predis­posing her to breast, ovarian and other cancers, as well as an extensive family history of cancer. Forbes searched for studies detailing the quality of life and dating scene for young, single women with mastectomies.

Her reason for turning to medical studies? “I live with an increased risk of cancer,” she says. “It’s for life. You have to know what you’re doing.”

Like Teicher and Forbes, many people affected by cancer recognize the importance of gathering the information scientific studies reveal about the disease and its treat­ments, including success rates, side effects and impact on quality of life. Or, they may want to visit clinicaltrials.gov and explore the possibility of enrolling in a trial. However, the complex language used in these research papers and listings can make this a difficult task.

Luckily, after becoming familiar with the documents’ structure and commonly used language, even those without training in the clinic or lab can understand the findings that are relevant to them.

^{"You don’t always have to trust the information. Just take from it what you can. The more information you have, the more you’re able to advocate for yourself.”— Brandi Forbes, previvor}

GET FAMILIAR WITH THE FORMAT

Learning how to read a paper that discusses the results of a clinical study can be challenging, even for those in the field. “This is a skill set we teach to medical students,” says Terry Davis, Ph.D., a professor of medicine who specializes in health literacy at Feist-Weiller Cancer Center at Louisiana State University Health Shreveport.

Most people will not understand a paper about a medical study the first, 10th or 20th time they read it, Forbes says. “There’s nothing wrong with having one window up with the article and another with a dictionary. To this day, that’s how I read an article,” she says.

For those new to medical studies, experts recommend approaching them the way Teicher did: Start with the abstract, which is at the top of the document and summarizes the trial or experiment and its findings.

Published studies are organized in a standard format, usually with the abstract followed by an introduction that offers context and the reason for the study. The next sections cover the method of research and the results; finally, a discussion section includes the researchers’ conclusions, their significance and implications, and possible next steps.

Here are the finer details to watch for.

Phase of a clinical trial: When a study involves researchers assigning patients an intervention — a drug, a surgical or radiation method, a medical device or other therapy — it’s known as a clinical trial. The trial’s phase explains where the study fits into the research timeline. On the early end is a phase 1 trial, a safety study to look for a treatment’s side effects and, when drugs are being tested, the optimal dose, says Kelly Owens, Ph.D., director of education and research at Facing Our Risk of Cancer Empowered (FORCE), an advocacy and support organization. A phase 2 trial tests a treatment’s effectiveness and continues to monitor side effects. Phase 3 — the largest — compares the experimental intervention with the current standard to determine if it is better, potentially confirming the results of earlier trials and further testing the therapy’s effectiveness and safety. “The phase 3 trial is what leads into drug approval,” says Owens — if the Food and Drug Administration (FDA) determines that the results are convincing.

Preclinical studies, which test therapies before they are ready to be tried in humans — for instance, using mice or human cell lines — are less relevant to patients, who, of course, can’t participate. Plus, the results may not hold up when the treatments are tried later in research in humans.

Size: There is no standard number of participants in a clinical study, says Audrey Riffenburgh, Ph.D., president of Health Literacy Connections (formerly Plain Language Works). Size depends on the study phase and the disease involved. A phase 1 trial has a small number of partici­pants, whereas phase 3 will be larger. A study in patients with breast cancer may have more participants than one of people with a rare cancer.

In a research paper, the total number of participants is often described with a capital “N” — for instance, N = 22. The number of patients in a single study arm (the term used for a group) or who have a certain characteristic is typically described with a lower-case “n.”

Criteria: Studies specify who is included and excluded, with criteria such as cancer type and stage, age, race, disease characteristics, previous treatments and other medical conditions, says Connie Arnold, Ph.D., a professor of medicine and a health literacy specialist at Feist-Weiller Cancer Center. Patients interested in enrolling should make sure their own circumstances match the criteria.

Design: The gold standard is a prospective clinical trial that’s double-blind, says Owens, which describes many phase 3 trials.

In a double-blind study, neither patients nor doctors know which participants are getting the new therapy and which are getting an older treatment or placebo (an inac­tive treatment); this helps eliminate bias. In a single-blind study, only the doctor knows who is receiving which treat­ment. Sometimes a study can’t be blinded — for instance, if treatment consists of chemotherapy versus radiation.

To further reduce bias, a study can be randomized, meaning that patients are randomly assigned to each treatment group.

A prospective study evaluates patients in real time, from the experiment’s start to its end. A retrospective study involves individuals who had a specific disease during a certain period of time. The researchers review the selected patients’ medical records to compare treatments and results from that time period. Although a retrospective study can generate useful findings, a prospective study’s design ensures that patients in each arm receive exactly the same treatments, so it’s a more precise way to test a therapy, Owens says.

Funding: It’s helpful to know who paid for the study. “If it was funded by pharma, I’ll have my radar up,” says Riffenburgh, “but if it was funded by pharma and double-blind, I’m more comfortable.” A study designed by academics and run in multiple institutions, with medica­tion supplied by a pharmaceutical company, increases experts’ confidence of an unbiased experiment. In either case, the FDA carefully scrutinizes later-stage trial results and questions the investigators in panel sessions before deciding whether to approve or reject a treatment for a specific use.

Endpoints: The primary endpoint refers to the study’s most important measure of a therapy’s safety or effec­tiveness, Owens says. The primary endpoint may be overall survival (OS), meaning that researchers will count how many participants were alive during a set period during or after treatment. Another common endpoint is progression-free survival (PFS), which measures how many patients survived a certain length of time without their disease returning or growing.

Ideally, OS increases with a new drug or drug combination, Owens says. However, if just PFS lengthens, that means that, on average, patients spend more of the time they have without their cancer worsening or requiring treat­ment, which may improve their quality of life. “From a science point of view, it tells you you’re on the right track,” Owens adds.

Progression endpoints aren’t always reached, but that often indicates that a treatment has worked very well. Still, Forbes appreciates longer-term studies with follow-ups that measure endpoints over time. As a younger person, she wants to see what happens to people five, 10 or 15 years down the line.

Results: This section contains crucial information — whether the study met its endpoints. Usually, this part of a paper explains whether a treatment improved PFS or OS, as well as if other endpoints were reached and by how much. It also may discuss the frequency of certain side effects. However, the statistics can be confusing, no matter what a person’s education level, so readers benefit from knowing which information is most relevant to them. Things like P values, hazard ratios and confidence intervals, as well as statistics such as area under the curve, help explain whether a treatment’s impact is due to more than random chance but are not necessary to the layperson’s understanding of the findings. A “statistical analysis” section found in some studies is even more complex.

Eva May, who received a diagnosis of breast cancer 10 years ago, says she understands the statistics in studies but tends to skip over them when deciding whether find­ings are of value to her. “I don’t usually need to analyze the detailed statistics to know if the results are meaningful and credible,” as there are enough other factors to consider, the Cary, North Carolina, resident says.

Conclusion: In this section, the authors explain the importance of the findings (whether positive or nega­tive), any study limitations, the results’ implications for clinical care or scientific understanding, and what further research should be conducted to move the field forward.

Publication Venue: Just as many might consider the Washington Post more trustworthy than a tabloid, medical journals have different reputations for accuracy. The most respected are peer-reviewed journals like the New England Journal of Medicine, JAMA, Nature and Cell. Submissions are anonymously reviewed by scientists who evaluate whether the study was done properly and the conclusions match the data, Owens says.

It’s also helpful to see which reputable organizations announce the study results, such as the American Association for Cancer Research (AACR) or the American Society of Clinical Oncology (ASCO). May tends to give more credit to studies endorsed by organizations like these.

Publication date: Findings from a 2005 study may be outdated compared with those of a 2015 study. However, the importance of recency can vary by disease, Riffenburgh says, as some cancers have not had new treatments approved in years.

^{Eva May, a survivor of breast cancer, has learned that she can understand a study’s basic findings even if she ignores complex statistical information.}

SEEK OTHER SOURCES

Those looking for simple summaries of studies and other cancer research information may want to turn to advocacy organizations such as the American Cancer Society (cancer. org). Other reliable sources: scientific and government organizations like ASCO and its patient-centric website, cancer.net; the National Comprehensive Cancer Network; AACR; and the National Institutes of Health, which provides funding to researchers and requires each to provide a plain-language summary when publishing findings.

The National Cancer Institute offers a website for patients and a blog, Cancer Currents, that is frequently updated with summaries of recent clinical studies, written in lay terms.

May receives newsletters from AACR and ASCO. “Sometimes those are pretty complex, but when there’s an announcement for a big discovery, I can read the headline. If it’s applicable, I can continue reading,” she says.

FORCE offers the XRAYS program, funded by the Centers for Disease Control. This program explains selected original research studies, noting for whom they are relevant. It also reviews media articles about the studies, rating their scientific accuracy. “They take these big research studies and reword them so anyone can under­stand them,” Forbes says. That can save time, she adds.

LOOK BEYOND THE HEADLINES

Reading about scientific research in the mainstream media is hit or miss. “The headlines are designed to get you interested,” Arnold says, but notes that sometimes they don’t reflect the study’s intent.

Media reports also may give facts but mislead readers, such as stating that a drug increases OS by a very large percentage but not mentioning that, in relative terms, it only prolonged life by a month. Occasionally, irresponsible outlets, particu­larly online, may sensationalize results to increase readership and even depart from the authors’ actual conclusions.

Pay attention to not only where the findings are published but also the sources of information and commentary. Does the article reflect one person’s opinion, insights from multiple sources, information from a study or a combination of those? Does it place the findings into context with other published research, and are the results similar?

Owens checks to see if the research was first published in a journal. If it’s presented at a meeting but not yet published, the scientific community hasn’t had an opportunity to vet it. “Sometimes the devil is in the details. Journals may make them tone it down,” Owens says.

PARTNER WITH YOUR DOCTOR

No matter how skilled they are at reading research studies, patients, survivors and caregivers should discuss the findings with their doctors. “It’s a lot of jargon,” Arnold says, and results need to be interpreted, with judgments made regarding the treatment’s appropriateness for the individual.

Doctors aren’t always recep­tive to patients’ desire to discuss medical studies. Teicher, Forbes and Riffenburgh, in her experi­ence as a patient, all had doctors either ignore or get angry with them for bringing in research to discuss. One doctor told Teicher: “You don’t know what you’re reading. Just stop reading.” She switched doctors. Her current doctor tells her to interpret what she can and then ask questions.

It can be awkward to ask a doctor about a medical study. “We’re raised to listen to doctors and trust them, to do what they say,” Forbes says. “But we have access to information we didn’t have 15 to 20 years ago. Now we’re active participants in our treatment plans.”

May prints out the studies she wants to discuss with the doctor. “It’s made it more of a partner relationship,” she says.

Doctors can discuss the risks and side effects shown in a study. The findings may be modest, like PFS increasing from 12 months to 13 months, on average. Even if the PFS isn’t very different, the treatment might improve quality of life, reduce side effects or be more convenient — for instance, if it’s given in pill versus IV form.

Owens reminds patients that a study is just one test, and despite the tendency to indicate either a great result or a failed treatment, “the truth is usually in between,” she says. With more time and information, the treat­ment’s story will change. “In public,” she says, “that process isn’t always understood.”

Studies should not scare people but instead empower them. “You don’t always have to trust the information. Just take from it what you can,” Forbes says. “The more information you have, the more you’re able to advocate for yourself.”