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Understanding Cancer Research Study Design and How to Evaluate Results

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Approved by the Cancer.Net Editorial Board, 04/2018

Doctors and scientists conduct research studies to find better ways to prevent and treat cancer. Depending on the questions they want to answer, researchers can design these studies in different ways. No study design is perfect. Each has strengths and drawbacks. It is important to understand a study’s design. By doing this, you can understand the results to know if they apply to your situation.

In cancer research, there are 2 main types of research studies:

  • Experimental studies. This type of study provides an intervention, such as a new treatment. The intervention is given to a group of people. Then, researchers compare their results to those of another group that does not receive the intervention. This other group is known as the control group. The researchers choose who does and does not receive the intervention either randomly or through a selection process. Experimental studies help researchers learn more about how cancer starts or spreads. These studies can also test new imaging techniques and explore quality of life issues.
  • Observational studies. This type of study involves observing groups of people in a natural setting and looking at a specific result. A result may include whether 1 group of people has more cancer diagnoses than another group. In these studies, the researchers cannot control the intervention, such as a person’s weight or whether they took vitamin supplements. These studies are often described as epidemiologic. Epidemiology involves studying how different risks cause or spread a disease in a community.

Types of experimental studies

Experimental studies are more reliable than observational studies. This is because the volunteers are placed in the intervention or control group by chance. This reduces the likelihood that the assumptions or preferences of the researchers or volunteers will change the study results. Such assumptions or preferences are called bias.

This type of study also helps researchers to better find and control other factors, such as age, sex, and weight. These factors can affect the results of the study.

Researchers may also consider certain factors when choosing people to enroll in an experimental study. They could be based on type of cancer, stage of the disease, or whether the cancer has spread.

One of the most common types of experimental studies is the clinical trial. This is a research study that tests a medical intervention in people. Clinical trials test:

  • The effectiveness or safety of a new drug or combination of drugs
  • A new approach to radiation therapy or surgery
  • A new treatment or way to prevent cancer
  • Ways to lower the risk of cancer coming back

Doctors and researchers conduct clinical research in segments called phases. Each phase of a clinical trial provides different answers about the new treatment. For instance, it can show the dose, safety, and efficacy of the treatment. The efficacy is how well the treatment works. There are 4 phases of clinical trials.

In a clinical trial, volunteers are usually selected by chance to either be in the treatment or control group. Researchers can prevent bias in a clinical trial by keeping volunteers and/or themselves from knowing how the volunteers are grouped. This is a process known as “blinding.”

Types of experimental studies include:

  • Double-blind randomized trial. Most scientists believe this type of clinical trial will produce the best evidence in a study. Neither the volunteers nor the researchers know who belongs to a treatment or control group until the study ends.
  • Single-blind randomized trial. In this type of trial, the volunteers do not know whether they belong to a treatment or control group. But the researchers know.
  • Open/unblinded trial. Both volunteers and researchers know who belongs to each test group in this type of study. This occurs when it is not possible to use blinding. For instance, the study could compare a surgical treatment to a drug.

Types of observational studies

In observational studies, researchers have less control over the study volunteers. This means that certain factors could affect the results. These studies, however, are useful in providing initial evidence that can help guide future research.

Types of observational studies include:

  • Case-control studies. These types of studies compare 2 groups of people. For instance, they could compare those who have cancer (the case) and those who do not (the control). Researchers may look for lifestyle or genetic differences between the 2 groups. By doing this, they hope to find out why 1 group has a disease and the other group does not. These studies are conducted retrospectively. That is, they are researching what has already happened.
  • Cohort studies. These studies are prospective, which means that researchers study the event as it occurs. They monitor a group of people for a long time and track something. For example, they could track any new cancer diagnoses. This type of study can assess whether certain nutrients or actions can prevent cancer. This approach can also find cancer risk factors. For instance, cohort studies have looked at whether postmenopausal hormone replacement therapy increases the risk of breast cancer.
  • Case reports and case series. These studies are detailed descriptions of a patient’s medical history. The individual patient descriptions are called case reports. If many patients receive a similar treatment, the case reports may be combined into a case series. The results of case series studies are descriptions of patients’ histories within a specific group. As such, they should not be used to determine treatment options.
  • Cross-sectional studies. These studies examine how diseases interact with other factors within a specific group at a point in time. But because these studies only measure interactions at a single point in time, they cannot prove that something causes cancer.

Types of review articles

A large number of cancer research studies are published every year. Given this, it is challenging for doctors, as well as interested patients and caregivers, to keep up with the latest advances. Research studies published in journals are constantly shaping and reshaping the scientific understanding of that subject. No single study provides the final word on a topic, type of cancer, or treatment. As a result, review articles, which evaluate and summarize the findings of all published research on a certain topic, are extremely helpful.

Types of review articles include:

  • Systematic reviews. These articles summarize the best available research on a specific topic. Researchers use an organized method to locate, gather, and evaluate a number of research studies on a particular topic. By combining the findings of a number of studies, researchers are able to draw more reliable conclusions.
  • Meta-analyses. These studies combine data from several research studies on the same topic. By combining these data, a meta-analysis can find trends that are hard to see in smaller studies. But if the single studies were poorly designed, the results of the meta-analysis may not be useful.

Evaluating research studies

Here are some tips for finding out the quality of a research study:

  • Find out if the journal uses a peer-review process. Results from a study are more reliable if they are peer-reviewed. This means that researchers who are not a part of the study have looked over and approved the design and methods.
  • Look at the length of the study and the number of people involved. A study is more useful and credible if the same results occur in many people across a long time. Studies of rare types of cancer or cancers with a poor chance of getting better are an exception to this rule. This is because there are a small number of patients to study. Also, when looking at the length of the study, it may be suitable for some clinical trials to be shorter. For instance, cancer prevention trials are often much longer than treatment clinical trials. This is because it usually takes longer to figure out if a prevention strategy is working compared to a treatment.
  • Consider the phase of the study when learning about new treatments. Phase I and II clinical trials usually tell you more about the safety of a treatment and less about how well it works. These studies tend to have a smaller number of patients compared to phase III clinical trials.  Phase III clinical trials compare a new treatment with the standard of care. “Standard of care” means the best treatments known. Doctors consider phase III clinical trials to be the most reliable.
  • Find out if the study supports or contradicts current research. New results are exciting, but other researchers must validate the results before the medical field accepts them as fact. Review articles like systematic reviews are of special interest. They review and draw conclusions across all of the published research on a specific topic.
  • Watch out for conclusions that overstate or oversimplify the results. Each study is a small piece of the research puzzle. Medical practice rarely changes because of the results of a single study.

Questions to ask your health care team

Always talk to your health care team about what you find in an abstract or study. If you have reviewed a study that suggests a different approach to cancer treatment, do not stop or change your treatment. First talk with your health care team about how the study relates to your treatment plan.

Consider asking your health care team the following questions:

  • I recently heard about a study that used a new treatment. Is this treatment related to my type and stage of cancer?
  • What type of journals should I read to learn more about my type of cancer?
  • Should I consider being a part of a clinical trial?
  • What clinical trials are open to me?
  • Where can I learn more about clinical trials?

Research on Causes of Cancer

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Why Research on Causes of Cancer Is Critical to Progress against the Disease

Cancer can be caused by many things, including exposure to cancer-causing substances, certain behaviors, age, and inherited genetic mutations.

Studying the causes of cancer helps researchers understand the process of carcinogenesis and identify genetic, environmental, and behavioral risk factors for cancer. This knowledge can lead to new ways of preventing and treating the disease.

Research on the causes of cancer also creates opportunities to improve public health, not only by identifying cancer risk factors in populations, but also by providing data that regulatory agencies can use to set safety standards or reduce exposure to toxins that are found to be associated with cancer. Findings from this area of research can also inform the development of advances such as safer computed tomography (CT) scans and risk-reducing surgeries.

Researchers use many different approaches to identify potential causes of cancer, from cell-based and animal studies to human observational studies. Research in basic cancer biology can reveal the mechanisms by which biological, chemical, and physical carcinogens initiate and promote cancer. Genetic analyses, such as genome-wide association studies, exome sequencing, and whole-genome sequencing, allow researchers to identify genetic changes that may be associated with cancer risk. Epidemiological approaches—including cohort studies, case-control studies, exposure-assessment studies, family studies, and genomic studies—are used to identify possible causes of cancer and study the patterns of risk in large populations.

Another approach, known as descriptive epidemiology, characterizes trends in cancer incidence and mortality within a given population, between populations over time, and in relation to overall patterns of exposure in populations to yield clues that may point researchers to cancer causes and risk factors. This type of research can also identify emerging trends in cancer incidence.

Opportunities in Research on Causes of Cancer

Advances in technology are improving how we determine and measure risk factors, enabling researchers to store and access findings in online databases, and allowing teams of investigators worldwide to pool data on an unprecedented scale. Multidisciplinary research teams are increasingly common and often include a range of experts, including epidemiologists, physicians, computational biologists, statisticians, oncologists, toxicologists, and geneticists.

Technological advances have also led to more accurate studies of substances in the environment suspected of causing cancer. Developing devices that can accurately measure environmental exposures and biochemical assays in biologic specimens that might be associated with cancer could improve researchers’ ability to identify cancer-causing agents.

Identifying people at highest risk of cancer, such as those with an inherited susceptibility to cancer or those who have been exposed to carcinogens, creates opportunities to develop risk prediction models and allows health providers to focus prevention and screening interventions on those most likely to benefit.

Challenges in Research on Causes of Cancer

Demonstrating cause-and-effect relationships in population studies examining potential cancer risk factors is a challenge because there are often many possible explanations for observed associations between a risk factor and cancer. Rare cancers and uncommon exposures, in particular, present challenges for researchers studying the causes of cancer. New statistical methods may be needed to improve the analysis of datasets of all sizes from these studies.

When studying certain exposures, such as dietary exposures, identifying which component is associated with an increased or decreased risk of cancer can also be a challenge. Retrospective studies have additional limitations, such as participants’ inability to accurately remember and report past exposures or exposure levels.

There is a continual need for new and improved techniques for measuring risk factors and exposures to potential causes of cancer. For example, studies that estimate radiation exposures among an exposed population must also quantify the uncertainties inherent to those estimates.

To identify cancer causes and risk factors that may be experienced by only a portion of the population, very large studies may be needed to have the statistical power required to establish an association.

Investigating interactions between genes and environmental exposures that have been associated with cancer is a challenge because some of these studies involve enormous data sets and require sophisticated computational analyses. Once a causative agent has been identified, another challenge is figuring out how to reduce a person’s exposure or ameliorate its harmful effects.

Although genome-wide association studies can point to chromosomal regions associated with cancer risk in certain populations, additional studies and analyses are needed to identify the specific genetic changes involved and to understand how they play a role in the development of cancer.

NCI’s Role in Research on Causes of Cancer

NCI funds extramural research on the causes of cancer and conducts intramural research in this area. The intramural research program allows the institute to conduct studies that require long-term, sustained support and provides NCI with the flexibility to redirect resources, when necessary, to respond quickly to emerging public health concerns.

NCI and NCI-funded researchers aim to understand the exposures and risk factors that cause cancer, as well as the genetic basis for cancer development.

Studies conducted by the NCI Cohort Consortium, for example, seek to identify factors (including environmental, lifestyle, and genetic) that may influence cancer risk. The consortium is a partnership between intramural and extramural investigators that pools the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies. The consortium consists of investigators responsible for more than 50 cohorts that include more than 7 million people in the United States and around the globe.

Intramural and extramural investigators also seek to identify ways to translate these research findings into tangible benefits to prevent cancer, identify and monitor those at risk, and develop clinical and public health interventions.

Environmental and Behavioral Risk Factors

NCI’s Division of Cancer Epidemiology and Genetics (DCEG) and the Epidemiology and Genomics Research Program in NCI’s Division of Cancer Control and Population Sciences (DCCPS) conduct and fund research to identify and evaluate a range of exposures and risk factors that may be associated with cancer, including:

DCEG researchers and those funded by DCCPS are also studying risks of second primary cancers. Nearly one in five cancers occurs in an individual with a previous diagnosis of cancer, and these second cancers are a leading cause of morbidity and mortality among cancer survivors. Research on treatment, lifestyle, environmental, and medical history factors associated with second cancers is ongoing, as is research on genetic susceptibility to second cancers.

Genetic Factors

NCI and NCI-funded investigators are also studying genetic factors that may predispose individuals to cancer and gene–environment interactions in cancer risk using approaches such as genome-wide association studies and whole genome scans.

Changes in an individual’s genes, including gene mutations, genetic modifiers, and polymorphisms, can alter his or her lifetime risk of cancer. To explain the genetic factors that influence a person’s risk for cancer, NCI and NCI-funded investigators are:

  • conducting human genetic studies to identify and validate key susceptibility genes and their modifiers using knowledge gained from gene expression profiles and protein “fingerprints”
  • identifying genetic and environmental factors that influence the cancer epigenome (i.e., chemical modifications to DNA that do not involve DNA sequence changes)
  • defining the role of inherited or acquired genetic alterations, in combination with lifestyle factors and environmental exposures (such as radiation and chemicals), as important determinants of an individual’s cancer susceptibility
  • identifying new tumor suppressor genes and oncogenes, and elucidating their mechanisms of action
  • identifying, mapping, and characterizing genes and chromosome regions that are involved in tumor initiation and progression

For example, investigators in DCEG’s Radiation Epidemiology Branch are partnering with investigators from the Childhood Cancer Survivor StudyExit Disclaimer to conduct a genome-wide association study of second cancers in childhood cancer survivors.

NCI researchers are also studying a range of hereditary cancer syndromes that predispose affected individuals and their family members to cancer. These include inherited bone marrow failure syndromes, Li-Fraumeni syndrome, DICER1 syndrome, familial melanoma, and others. Studies of people with hereditary cancer syndromes help researchers understand the underlying biology of cancer risk and develop ways to improve the management of these disorders.

Such studies may also, indirectly, provide insights into the genetic basis for noninherited, or sporadic, forms of cancers. That was the case with research on familial kidney cancer by W. Marston Linehan, M.D., of NCI’s Center for Cancer Research (CCR).

How Exposures and Risk Factors Act

NCI supports and conducts research to understand the mechanisms by which external exposures and risk factors induce and promote cancer.

NCI’s Division of Cancer Biology (DCB) supports research investigating the role of biological agents and host factors that contribute to cancer. DCB’s Cancer Immunology, Hematology and Etiology Branch, for example, funds research on the role of the microbiome in cancer development and the influence of aging on cancer susceptibility. DCB also supports research to understand mechanisms by which carcinogens initiate and promote tumor development.

CCR researchers are trying to elucidate mechanisms that influence tumor initiation, promotion, and progression, including those associated with lifestyle, the environment, inflammation, the immune system, viruses, and host-tumor interaction.

NCI’s Office of HIV and AIDS Malignancy (OHAM) coordinates and oversees NCI research programs that focus specifically on HIV/AIDS and AIDS-associated cancers. For example, OHAM’s AIDS and Cancer Specimen Resource is a biorepository for HIV-infected human biospecimens that serves as a resource for investigators conducting basic research in the pathogenesis of AIDS-related malignancies.

 

Research on Causes of Cancer was originally published by the National Cancer Institute.

For Women with Breast Cancer, Regular Exercise May Improve Survival

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From: NCI Cancer Currents Blog
May 15, 2020, by NCI Staff

Physical activity is shown to help prevent breast cancer.

Getting regular exercise may increase how long some women with breast cancer live, results from a new study show. Credit: iStock

Getting regular exercise may increase how long some women with breast cancer live, results from a new study show. Women who engaged in regular physical activity before their cancer diagnosis and after treatment were less likely to have their cancer come back (recur) or to die compared with those who were inactive, the study found.

The study was unusual in that it collected information on the physical activity levels of women with high-risk breast cancer (cancer that is likely to recur or spread) at multiple time points—shortly before their diagnosis, during chemotherapy, and after completion of treatment.

“Our data strongly suggest that the more consistently active patients were, the better they did,” said lead study author Rikki Cannioto, Ph.D., Ed.D., of Roswell Park Comprehensive Cancer Center in Buffalo, NY.

And while survival was extended in women who consistently met federal Physical Activity Guidelines for Americans over time compared with those who did not meet the guidelines, “there was still a survival advantage for women who [were active but] didn’t quite meet the guidelines,” Dr. Cannioto said.

These results “provide evidence that physical activity at any point in time appears to be beneficial for breast cancer survivors,” said Joanne Elena, Ph.D., M.P.H., of the Epidemiology and Genomics Research Program in NCI’s Division of Cancer Control and Population Sciences (DCCPS), who was not involved with the study.

“This study gives us further evidence that being more physically active after a diagnosis of breast cancer is one of the ways that breast cancer survivors can take matters into their hands and improve their health and decrease their likelihood of dying,” said Kathryn Schmitz, Ph.D., M.P.H., an exercise oncology researcher at the Penn State College of Medicine, who also was not involved with the study.

The new study was published April 2 in the Journal of the National Cancer Institute.

Looking at Exercise Over Time

The findings come from the NCI-funded Diet, Exercise, Lifestyle, and Cancer Prognosis (DELCaP) study, led by Christine Ambrosone, Ph.D., also of Roswell Park. The study was embedded in a large clinical trial, led by the NCI-funded SWOG Cancer Research Network, that compared different chemotherapy regimens for women with high-risk breast cancer.

The physical activity analysis by Dr. Cannioto and her colleagues included 1,340 patients from the SWOG trial who also enrolled in the DELCaP study. Participants completed questionnaires about the type, frequency, and duration of recreational physical activity they engaged in at four time points: during the month before diagnosis, during treatment, and at 1 and 2 years after study enrollment. Participants were followed for up to 15 years or until death, with a mean follow-up time of 89 months (7.4 years).

Much, though not all, previous epidemiologic research describing the link between physical activity and cancer outcomes is based on physical activity data collected at only one time point, Dr. Cannioto said.

Using the questionnaire responses, the researchers determined whether participants had met the minimum 2018 Physical Activity Guidelines for Americans at each time point. The guidelines recommend that adults engage in at least 2.5 to 5 hours of moderate-intensity physical activity or 1.25 to 2.5 hours of vigorous-intensity aerobic physical activity per week.

Women with breast cancer who met the minimum physical activity guidelines both before diagnosis and at the 2-year follow-up (after treatment) had a 55% reduced chance of their cancer returning and a 68% reduced chance of death from any cause (not just breast cancer) compared with those who did not meet the guidelines at both times.

Among patients who did not meet the guidelines before diagnosis but met them at the 2-year follow-up, the chance of recurrence or death was reduced by 46% and 43%, respectively, compared with those who did not meet the guidelines at both times. The finding, Dr. Elena said, suggests that “it’s never too late to start exercising to derive benefits.”

The researchers also performed “time-dependent analyses,” which help to account for the fact that physical activity data was collected over multiple time points,” Dr. Cannioto explained.

These analyses showed that, compared with inactive patients, the likelihood of death from any cause was reduced the most among highly active patients, but even patients who regularly engaged in low levels of physical activity saw a substantial survival benefit.

These findings “are good news for breast cancer patients, who can be overwhelmed by the physical activity guidelines, especially during treatment,” when they may be severely fatigued or in pain, Dr. Cannioto said. However, she emphasized, to achieve optimal health benefits, patients and survivors should still strive to meet the guidelines when they are able.

Reducing Self-Reporting Inaccuracies

Although physical activity information that people report themselves is not always accurate, the detailed questionnaire used in this study is likely to provide a better estimate of the amount of exercise that people do than a single question or brief survey would, “giving stronger credence to the findings,” Dr. Schmitz said.

In addition, evaluating the findings according to whether participants did or did not meet the physical activity guidelines, as the study authors did, rather than on how many minutes of physical activity people did each week, is also likely to reduce inaccuracies, said Richard Troiano, Ph.D., also of DCCPS’s Epidemiology and Genomics Research Program.

One limitation of observational studies like DELCaP and the many other epidemiologic studies that form the basis for the latest exercise guidelines for cancer survivors, Drs. Troiano and Elena said, is that such studies cannot definitively prove a cause-and-effect relationship between physical activity and improved survival or reduced risk of recurrence.

That’s because it’s also possible that “the people who feel better are more likely to be able to be physically active than those who are sicker,” Dr. Troiano explained.

Another limitation is that the DELCaP study only had information on patient deaths due to any cause, rather than on deaths due specifically to breast cancer, and physical activity may have less of an impact on breast cancer mortality, Drs. Schmitz and Troiano noted.

Move as Often as You Can, Whenever You Can

“This study comes at a time when we already have national and international physical activity recommendations for cancer survivors, for the purpose of reducing the risk of recurrence and mortality,” Dr. Schmitz said, and the new findings reinforce these recommendations.

It’s important to keep in mind, however, that “physical activity is not the only factor that determines whether breast cancer will recur, and it certainly is not the only determinant of death. It’s just one piece of the puzzle,” Dr. Elena said.

“We don’t want someone to think, ‘If I exercise enough, I won’t have a recurrence,’” she continued. “But if you can add physical activity into your day, it is likely to influence many types of health outcomes for breast cancer survivors.” That includes quality of life, anxiety, fatigue, and the ability to tolerate treatment, as well as the risk of dying.

The bottom-line message for breast cancer survivors, Dr. Elena concluded, is “Move as often as you can, when you can.”

FirstHealth Awarded for Clinical Trial Participation

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PINEHURST — Several hundred patients are now actively involved or are being followed in studies conducted by the FirstHealth of the Carolinas Clinical Trials program.

The program recently received a Gold Seal Award from the Southeast Clinical Oncology Research Consortium and the National Cancer Institute.

A group of community oncologists, surgeons, radiation oncologists and urologists in the Southeastern United States who are committed to bringing cancer clinical trials to their communities, SCOR helps facilitate the connection between affiliate members and patients and the clinical trials they seek. This allows affiliates to administer state-of-the-art cancer treatment to patients in need. >>read more

(from Richmond County Daily Journal)