Study: “High-Level” Orthopedic RCTs Need to Power-Up
Research from several Philadelphia-based institutions might be a bit alarming for those relying on “high-level” research studies. The proportion of RCTs in orthopedic surgery in which the null hypothesis is rejected are inadequately powered. A team from The Rothman Institute, Children’s Hospital of Philadelphia, Thomas Jefferson University Hospital, and Drexel University has found that it’s wise to be a bit skeptical when it comes to randomized controlled trials (RCTs).
Surena Namdari, M.D. is an orthopedic surgeon with The Rothman Institute. He told OTW, “There has been increasing focus in the orthopaedic literature on improving the quality of our research initiatives, and in particular, on producing level I, randomized-controlled trials. Unfortunately, we felt that a substantial number of these trials are underpowered for the primary study question being investigated. Because randomized-controlled trials are often seen as the best quality evidence on which to base clinical decision-making, we believed that underpowered studies could send an inaccurate, and potential dangerous, message to the reader.”
Dr. Namdari and his colleagues reviewed all English-language RCTs appearing in the orthopedic literature from January 2012 to December 2013. “We were surprised to find that a substantial number of randomized-controlled trials either did not report a power analysis or were underpowered for the main study question. In particular, many studies that reported ‘no clinical difference’ between groups were underpowered. It was interesting to see that studies with high levels of evidence frequently were not sufficiently powered to accurately draw conclusions from the reported data.”
“We hope that this paper alerts readers, investigators, and journal editors/reviewers about the prevalence of underpowered randomized controlled trials in the orthopaedic literature. While it is understood that, when reporting the lack of clinical differences between study groups, adequate sample size must be ensured in order to generate an acceptable level of type-II error, this was absent in almost 30% of the analyzed studies. Hopefully by drawing attention to this subject, increased scrutiny will be placed on studies that report “no clinical difference” but may be underpowered to do so. Simply said, ‘high-level of evidence’ does not necessarily translate into “high-quality evidence” for clinical decision making.”
“As the clinical literature in orthopaedics continues to expand, researchers must strive to achieve adequate power and thus add relevant findings (both positive and negative) on which to base clinical decisions. In addition, orthopaedic surgeons should pay particular attention to whether studies are adequately powered to support their negative findings and journal editors and reviewers should be wary of underpowered RCTs when considering manuscripts for publication.”
Correct DDH, Prevent Osteoarthritis at Birth?!
If it’s never been attempted before, The Rothman Institute just may try it. This time, Rothman researchers have set out not only to help newborns, but to make those little patients healthier as they age. Alexander R. Vaccaro, M.D., Ph.D., MBA, is president and the Richard H. Rothman Professor and chairman of the Department of Orthopaedic Surgery at the Rothman Institute. He told OTW, “Led by George Feldman, Ph.D., D.M.D., we have focused on finding an accurate diagnostic test for Developmental Dysplasia of the Hip (DDH). Such a test could be used to diagnose and non-invasively correct this potentially debilitating disorder. DDH affects about 1-2 individuals per 1, 000 on average with much higher ‘pockets’ of incidence in parts of the United States, Italy, and South America.”
“DDH is a complex disease with both an environmental and a strong genetic cause. In DDH the hip socket does not fully form, causing the head of the femur to easily dislocate and inducing abnormal wear of the cartilaginous lining of the joint. This leads to early onset osteoarthritis of the hip in young adults. The really exciting challenge that this disorder presents is that DDH can be corrected non-invasively in newborns if detected early by using a Pavlik harness, a device which immobilizes the hips of newborns for about six weeks. This immobilization allows their hip sockets time to fully develop. Current tests involving manipulation of the femur at birth fail to detect subtle forms of DDH. It is these undetected individuals that account for 40% of all osteoarthritis of the hip in 20-40 year olds.”
“Using the DNA from large families we have identified specific mutations that seem to make individuals susceptible to DDH. We think that this will bring us closer to an accurate early diagnostic test for this disabling disorder.”
“Before the advent of high through-put, next generation sequencing, many research groups tried to ‘guess’ which DNA variants within candidate genes might be causing DDH with mixed success. Early family-based genetic studies would often narrow the region where the culprit mutation resides but could not identify it precisely. We have used both the powerful older tool of genetic linkage analysis to narrow the region where the causative mutation resides in large families and next generation sequencing to precisely identify the genetic defect.”
“Another aspect of determining the genetic cause of this disorder is the work going on with dogs. Canine hip dysplasia (CDH), as DDH acts in humans, causes early and disabling osteoarthritis of the hip. We believe that some of the same genes that cause dysplasia in dogs will be acting in humans. Very large canine pedigrees exist where susceptibility to CDH is transmitted across generations, therefore increasing the statistical power available for identifying causative mutations. We are currently collaborating with a veterinarian, Rory Toddhunter [BVSc, PhD] at Cornell, in a trans-species DNA mapping project for DDH.”
Asked about the most difficult aspect of such work, Dr. Vaccaro stated, “Once mutations that are thought to cause DDH in humans are found their true functional role must be proved. To do this human mutations must be shown to alter hip morphology in another animal, often mice. This can prove to be difficult. We have preliminary evidence that one of the mutations we found in our large human family causes a mismatch in hip socket and femur head size in mice where the mouse gene affecting the human family in our study has been ablated.”
John Dormans, M.D. Named Orthopedic Chair at Texas Children’s Hospital
The new recipient of the L.E. Simmons Chair in Orthopedics at Texas Children’s Hospital is John Dormans, M.D. Not only is Dr. Dormans a professor of orthopedic surgery at Baylor College of Medicine, but he has served as chairman of Texas Children’s Board of Trustees from 2003-2004.
Dr. Dormans, who primarily treats complex spinal disorders and those in need of orthopedic oncology care, previously served as president of the Pediatric Orthopaedic Society of North America and the International Society of Orthopaedic Surgery and Traumatology. He is currently president of World Orthopedic Concern.
Dr. Dormans obtained his undergraduate degree at Indiana University in Bloomington, Indiana, and earned his medical degree at the university’s school of medicine in Indianapolis. He undertook an orthopedic surgery at Michigan State University, followed by a clinical pediatric orthopedic fellowship at The Hospital for Sick Children in Toronto, Ontario. Dr. Dormans has also done post-graduate work at the Harvard School of Public Health, Children’s Hospital of Philadelphia and The Wharton School of the University of Pennsylvania.
Dr. Dormans told OTW, “This honor stemmed from the immense generosity of the Houston Endowment which wanted to recognize the years of leadership and support of Mr. L. E. Simmons to both the endowment and the hospital and support the growth and reorganization of Orthopedics at Texas Children’s Hospital.”
Asked about his departmental plans for the next six months, Dr. Dormans commented, “My long term goal is make Texas Children’s Orthopedics one of the top programs in the world. To do that, I am focusing my efforts on three main areas—recruitment, operations and facilities, and reputation and expertise.”
“A more robust staff will allow the Orthopedics Department to accommodate the requests it currently gets from patients and families across the region, throughout the United States and across the globe. It also will position the department for tremendous growth in both its general practice and subspecialty areas. We will double the number of specialty trained MD experts in Orthopedics in the first 12 months.”
“Operationally, I am making several changes that will help make the department run more efficiently and become more competitive. We will expand and reorganize our Advanced Practice Practitioner (APP) model to create a collaborative care model by adding an additional six nurse practitioner APPs. This will help make the department’s outpatient visit process run more smoothly (e.g. revised visit scheduling etc.) The department will also double its administrative support staff, create a robust clinical research program, add additional administrative leadership support and add dedicated surgical schedulers, in additional to hundreds of other ‘operational’ improvements. We are also preparing for a Texas Children’s Hospital West Campus orthopedic faculty expansion, as well as the opening of Texas Children’s Hospital The Woodlands with a strong orthopedic presence. Additionally, we have reorganized our fracture care model.”
“Another aspect of operations I will focus on is information services and technology, getting the latest and greatest tools to aid our staff in doing the best we can to help the patients and families who seek expertise from our department.”
“Ultimately, I would like people to identify Texas Children’s as ‘the place to go’ to find answers to all of their pediatric musculoskeletal problems. With more than 30 physicians and advanced practice providers treating everything from minor fractures to complex disorders, our department at Texas Children’s is on the right track, and, the sky is the limit.”
