The College of Public Health’s Clinical Trials Statistical and Data Management Center (CTSDMC) contributed to a 2016 children’s migraine study that was recently selected by editors at the American Academy of Neurology as one of the most important advances of the year.
The CHAMP study, co-authored by biostatistics professor and CTSDMC director Christopher Coffey, found that prescribed medications are no more effective than a placebo when used to prevent migraines in children and teens. The study was published in the New England Journal of Medicine.
Bruce Cohen, professor of pediatrics at Northeast Ohio Medical University and a member of the academy’s editorial advisory board for the weekly publication, Neurology Today, identified the CHAMP study as one of only two studies that met the criteria for “Best Advances of 2016” in the Pediatric Neurology category. The designation is intended to highlight “the most important advances, policies, and professional issues that occurred during the past 12 months,” according to the publication.
Joe Cavanaugh, professor and head of the Department of Biostatistics, said the citation was “impressive recognition of a study that will clearly have a profound impact on the treatment of pediatric migraines.”
“Yet another example of the stellar research being conducted by our colleagues in the CTSDMC!” said Cavanaugh.
Congratulations to the Clinical Trials Statistical and Data Management Center, which contributed to a study that was named one of the New England Journal of Medicine’s Journal Watch Pediatrics and Adolescent Medicine Top Stories of 2016.
The study found that two pills frequently prescribed to children to prevent migraines were no more effective than a placebo, even though the two drugs—amitriptyline and topiramate—prevent migraines in adults.
The evidence was so overwhelming researchers stopped the trial early. The results were published in the The New England Journal of Medicine.
The study was conducted by Cincinnati Children’s Hospital Medical Center and the UI College of Public Health’s Clinical Trials Statistical and Data Management Center. Christopher Coffey, director of the CTSDMC and professor of biostatistics in the UI’s College of Public Health, says the data management center served as the data coordinating center (DCC) for the study. Coffey says UI researchers entered and cleaned the data using a web-based data entry system developed and maintained at the DCC.
The UI researchers also had primary responsibility for all statistical aspects of the study and analyzing primary study data. They were responsible for all data management, safety monitoring, and clinical site monitoring activities for the study.
Prescribed medications are no more effective than a sugar pill when used to prevent migraines in children and teens.
A study published Oct. 27 in The New England Journal of Medicine shows no significant differences among amitriptyline, topiramate, and placebo in reducing headache days or related disability.
“The study was intended to demonstrate which of the commonly used preventive medications in migraine was the most effective. What we found is that we could prevent these headaches with either a medication or a placebo,” says Andrew Hershey, MD, PhD, co-director of the Cincinnati Children’s Headache Center and senior author of the study. “This study suggests that a multi-disciplinary approach and the expectation of response is the most important, not necessarily the prescription provided.”
Researchers conducted the Childhood and Adolescent Migraine Prevention (CHAMP) study at 31 sites in the United States.
Cincinnati Children’s served as the Clinical Coordinating Center (CCC) for the study, and was responsible for all clinical oversight activities. The Clinical Trials Statistical and Data Management Center (CTSDMC) at the University of Iowa served as the Data Coordinating Center for the study. It had primary responsibility for data management, implementing the electronic data capture system, and all statistical aspects of the study.
Interpreting the Results
“The interpretation of these results is very challenging. In most situations, trials that fail to show benefit of an intervention do so because study participants do not improve. That was not the situation here. A majority of all study participants improved, regardless of their assigned treatment group,” says Chris Coffey, PhD, director of the CTSDMC and professor of biostatistics in the University of Iowa’s College of Public Health, and lead statistician for the study. “Further research is needed to better understand the results and to determine what future strategies might optimize the treatment of headaches in these childhood and adolescent populations.”
The 24-week clinical trial included 328 eligible patients. The trial used a clinically meaningful endpoint of a 50 percent or greater reduction in headache days from the 28 days prior to randomization to the final four weeks of the 24-week study. Sixty-one percent of those on a placebo saw the days they had a headache reduced by 50 percent or more.
For the two medication groups, 52 percent of those taking amitriptyline and 55 percent of those taking topiramate had this level of reduced headache days. The responder rates were not statistically different between the three groups.
Compared to placebo, those on the two active drugs had a significantly higher rate of side effects, including fatigue, dry mouth and, in three cases, mood alteration. Thirty-one percent of those on topiramate had paresthesia – a “pins and needles” tingling in the hands, arms, legs or feet.
The results raise questions about the best way to prevent migraines, particularly given that it’s unethical to prescribe a placebo without the patient’s knowledge, according to the authors. They add it’s likely the expectation of responding to a medication may override the actual biochemical and pharmacological changes that are thought to occur with pharmacotherapy.
Major pediatric headache centers, such as Cincinnati Children’s, incorporate a multi-disciplinary approach that includes acute therapy, preventive therapy and behavioral treatment in a systematic approach, says Hershey. The CHAMP study incorporated this approach across all 31 study sites to ensure uniformity.
“Our national team was hoping to develop evidence to drive the choice by medical providers of the first line prevention medication for helping youth with migraine, but the data showed otherwise, says Scott Powers, PhD, pediatric psychologist, co-director of the headache center at Cincinnati Children’s, and first author of the paper. “We see this as an important opportunity for health care providers, scientists, children, and families because our findings suggest a paradigm shift. First line prevention treatment will involve a multidisciplinary team approach and focus on non-pharmacological aspects of care. The good news is we can help children with migraines get better.”
Powers says the study also underscores the importance of conducting more research with a developmental focus on children and young adults. This will allow innovations that can be applied directly to a chronic illness of childhood.
The study was supported by the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health through grants U01NS076788 and U01NS077108.
Jeffrey D. Dawson and Christopher S. Coffey from the University of Iowa College of Public Health have been named 2016 Fellows of the American Statistical Association (ASA), the nation’s preeminent professional statistical society. Dawson is professor of biostatistics and associate dean for faculty affairs, and Coffey is professor of biostatistics and director of the Clinical Trials Statistical and Data Management Center (CTSDMC).
To be recognized as an ASA Fellow, each honoree must make outstanding professional contributions to and have exhibited leadership in the field of statistical science.
Dawson was recognized for his significant contributions to research in driving safety and cardiovascular health; for innovative methodological advances in the analysis of longitudinal, ordinal, and categorical data; and for service to the profession.
Coffey was honored for contributions to the design and analysis of clinical trials; for leadership in the coordination and conduct of clinical trials; for outstanding education and mentoring of statisticians, scientists, and clinical trialists; and for outstanding leadership and service to ASA and the profession.
They will be officially recognized at an awards ceremony August 2, 2016, during the Joint Statistical Meetings (JSM 2016) in Chicago.
The designation of ASA Fellow has been a significant honor for nearly 100 years. Under ASA bylaws, the Committee on Fellows can elect up to one-third of one percent of the total membership as fellows each year. Individuals are nominated by their peers in the association membership.
To be honored, nominees must have an established reputation and have made outstanding contributions in statistical science. The Committee on Fellows evaluates each candidate’s contributions to the advancement of statistical science and places due weight to published works, the position held with their employer, ASA activities, membership and accomplishments in other societies and other professional activities.
The American Statistical Association is the world’s largest community of statisticians and the second-oldest continuously operating professional society in the United States. Its members serve in industry, government and academia in more than 90 countries, advancing research and promoting sound statistical practice to inform public policy and improve human welfare.