Principle Investigators: Paul Gross and Richard Stevenson, M.D.
Sponsoring Institution: University of Virginia
Study Executive Committee
- Diane Damiano, PT PhD, Co-Investigator, National Institute of Health Clinical Center
- Paul Gross, Co-Principal Investigator, Cerebral Palsy Research Network
- Susan Horn, PhD, Co-Investigator, University of Utah
- Jacob Kean, PhD, Co-Investigator, University of Utah
- Unni Narayanan, MD, Co-Investigator, Hospital for Sick Children
- Garey Noritz, MD, Co-Investigator, Nationwide Children’s Hospital
- Jerry Oakes, MD, Co-Investigator, Children’s of Alabama
- Michele Shusterman, Co-Investigator, CP Daily Living/CP NOW Foundation
- Richard Stevenson, MD, Co-Principal Investigator, University of Virginia
Background and Significance
Cerebral palsy (CP) refers to a variable group of disorders affecting movement and posture, attributable to non-progressive injuries to the developing brain. CP is the most common physical disability of childhood, impacting individuals across the lifespan. No cure is imminent. For most children with milder CP (Class I-III on the Gross Motor Functional Classification Scale, GMFCS), neurological and/or orthopedic surgery is a central part of treatment to improve independent ambulation. A recent systematic review found that data are sufficient to justify surgical procedures, but no trials directly compare available options. Wide practice variation exists, as evidence is insufficient to match the best procedure with each child. In developing this project, an online community of parents of children with CP was surveyed about their perceptions of surgical decision making. Overwhelmingly, parents reported difficulty making a decision for surgery and challenges receiving consistent recommendations about timing, type, and extent of surgery.
Study Purpose and Aims
Our purpose is to determine the effectiveness of surgical interventions for ambulatory children with CP compared to non-surgical interventions using child and parent reported outcome measures that align with family goals. The fundamental study question is: which surgical procedure is associated with best outcomes for each child?
- Controlling for patient characteristics, to compare the effectiveness of orthopedic surgery, selective dorsal rhizotomy (SDR), neurotoxin injection, and PT alone in improving outcomes in children with bilateral spastic CP.
- Describe and compare types and rates of adverse events and complications associated with each treatment
- Explore whether there are specific surgical or intervention-related details highly associated with positive or negative outcomes, controlling for patient factors.
We will recruit 2000 children, aged 3-12, with bilateral spastic CP (GMFCS I, II, III; no prior lower limb surgery) receiving usual clinical care (at 23 sites) into this observational, pragmatic clinical trial. At least 1500 children will complete two years follow up within four clinically-determined comparator groups (n): orthopedic surgery (490), SDR (210), neurotoxin injection (340) and PT alone (460). Treatments will not be assigned, but chosen by families and clinicians. The primary outcome measure is the Lower Extremity/Mobility Cerebral Palsy Computer Adaptive Test, a validated condition-specific, parent-reported outcome measure of lower extremity related physical function. Secondary outcomes include: the newly developed patient and/or parent reported GOAL Questionnaire, the Edinburgh Gait Scale, and pediatric PROMIS measures of fatigue, pain, and anxiety.
The study will employ a comparative effectiveness design and analytic plan refined and utilized successfully by Co-I Dr. Horn. Past trials recruited large datasets (1000-2000 patients) with highly granular data collection and a range of objective outcomes. Statistical adjustment for medical comorbidities is a key part of this methodology using the pediatric Comprehensive Severity Index (CSI) to control for confounding variables and heterogeneity. This method enables causal inferences about treatments from observational data, and it has been used successfully in other rehabilitation studies (e.g. traumatic brain injury, stroke).
We will collect detailed descriptions of actual clinical practices to quantify and confirm the degree of practice variation, collect a comprehensive data set of specific patient characteristics, and determine their associations with a range of outcomes over the two years follow up. Patient and treatment variability are anticipated and desirable, with differences utilized as covariates in statistical analyses. This methodology places a strong focus on the effect of patient differences on outcomes. Important covariates will include severity of spasticity, deformity and functional status, which in prior work have demonstrated a large impact on outcomes and in some cases even surpassed treatment differences.
The investigative team includes parents of children with CP, orthopedic surgeons, neurosurgeons, neurologists, physiatrists, pediatricians, therapists, epidemiologists, engineers, and statisticians. The existing Cerebral Palsy Research Network (CPRN, cpresearch.net) provides the foundation for data collection and the 23 study sites are part of the CPRN Registry. In addition to the current standardized registry data, a comprehensive study data set with outcome measures will be collected.
In sum, our survey indicated surgical decisions are the most difficult decisions parents face in the care of their children with CP. These decisions cause great anxiety because parents do not have the anchors of information they need to fully assess potential benefits against risks for these procedures that affect their children permanently. RCTs have shown surgical interventions to be superior to physical therapy alone, but under ideal circumstances and over the short term. It is not yet known how surgical and non-surgical treatments compare under real-world circumstances over the longer term, or how variations within surgical interventions compare with one another. More details about the best treatments for specific patient groups are needed before additional RCTs should be done. Design aspects of RCTs that preserve internal validity, such as blinding or remaining within the assigned treatment group, are difficult to achieve in surgical studies, and our patient and family collaborators find randomization to be unacceptable in this clinical context. In short, the goal of this study is to change practice by identifying patient characteristics and surgical options associated with best outcomes that will help clinicians and parents choose the right treatment for the right child at the right time.
Cerebral Palsy (CP) is the most common physical disability of childhood. CP is a permanent disorder caused by an injury to the developing brain that causes problems with the motor system: walking, posture, or balance. Most children with CP walk independently; others use devices such as walkers, braces, and crutches; and some may use wheelchairs. This study focuses on children aged 3-12 years who can walk, either independently or with a device.
Children with CP often have stiff muscles that can lead to difficulty walking, abnormalities of tendons, bones and joints, and chronic pain. These problems may interfere with a child’s ability to participate in and enjoy life. There are several treatments or surgeries that can be performed to improve these conditions, but it is difficult to say which is best for a particular child. Parents count on their medical team to explain which option will help their child the most. However, the medical community does not have enough data to address parents’ concerns and help them understand what options are best suited for their child. This creates stress for families who are eager to support their child’s development and comfort yet fear putting their child through a procedure that may not be helpful or even worsen their condition.
Four categories of treatments will be studied. Doctors will recommend appropriate therapies, but the final decision of which kind of treatment the child will get is up to the parents. The first category of treatment is orthopedic surgeries, which loosen stiff muscles or adjust the bones in the hips, knees, or ankles. The second is a neurosurgical procedure called a selective dorsal rhizotomy that decreases muscle stiffness by stopping overactive signals from the brain by cutting some nerves in the spine. The third category is injection of medication into the muscles directly, which temporarily decreases the stiffness. The last group of patients will receive physical therapy, but no other procedure to directly address muscle stiffness.
We will recruit 2000 children with CP who are receiving these treatments. We will collect details about each child’s medical history and follow them for 2 years. We will collect information about how their parents decide whether to have surgery or not. If they have a surgery, we will collect information about it from the surgeon. Throughout the study, we will collect information about the child’s physical function and how they are participating as part of a family and community. Achievement of walking-related goals and quality of life, are some of the most important outcomes in the study. Parents of children with CP on our study team have played a vital role in helping us understand what outcomes are most meaningful, and have been full partners in the creation and design of the study.
Our goal is to help doctors and parents make better decisions about which children with CP should have which procedures, and at what ages they offer the best outcomes.
Site Principal Investigators
|A.I. du Pont Children’s Hospital||Freeman Miller, MD||Newark, DE|
|Boston Children’s Hospital||Benjamin Shore, MD, MPH||Boston, MA|
|Children’s Hospital of Colorado||Dennis Matthews, MD||Denver, CO|
|Children’s Hospital of Alabama||Brandon Roque, MD||Birmingham, AL|
|Cincinnati Children’s Hospital||Amy Bailes, PhD
Jilda Vargus-Adams, MD, MPH
|Columbia/Weinberg Cerebral Palsy Center||David Roye, MD||New York, NY|
|Gillette Children’s Specialty Healthcare||Michael Partington, MD||Minneapolis , MN|
|Johns Hopkins Medical Institutes||Ranjit Varghese, MD||Baltimore, MD|
|Nationwide Children’s Hospital||Jeffrey Leonard, MD
Garey Noritz, MD
|Phoenix Children’s Hospital||Taryn Bragg, MD
Michael Kruer, MD
|Primary Children’s Hospital/University of Utah1||Robert Bollo, MD
Jacob Kean, PhD
Susan Horn, PhD
|Salt Lake City, UT|
|Rady Children’s Hospital||Pritha Dalal, MD||San Diego, CA|
|Rehabilitation Institute of Chicago||Gadi Revivo, DO||Chicago, IL|
|St. Louis Children’s Hospital||Toni Pearson, MD||St. Louis, MO|
|Seattle Children’s Hospital||Kristie Bjornson, PhD||Seattle, WA|
|SickKids/Holland Bloorview||Unni Narayanan, MD, MPH||Toronto, ON Canada|
|Texas Children’s Hospital||Aloysia Schwabe, MD||Houston, TX|
|Texas Scottish Rite Hospital||Mauricio Delgado, MD||Dallas, TX|
|University of Florida, Jacksonville||Aga Lewelt, MD||Jacksonville, FL|
|University of Michigan||Ed Hurvitz, MD||Ann Arbor, MI|
|University of Texas Health Center-Houston||Manish Shah, MD||Houston, TX|
|University of Texas Medical Branch-Galveston||David Yngve, MD||Galveston, TX|
|University of Virginia2||Rich Stevenson, MD||Charlottesville, VA|
1Data Coordinating Center
2Clinical Coordinating Center
Patient and Stakeholder Partners Committee
|Jon Davids, MD||Stakeholder||Orthopedic Surgeon||Shriners of Northern California|
|Lizette Dunay||Stakeholder and Parent||Executive Director||CURE CP|
|Richard Ellenson||Stakeholder||CEO||Cerebral Palsy Foundation|
|Cynthia Frisina||Stakeholder and Parent||Executive Director||Reaching for the Stars|
|Vedant Kulkarni, MD||Stakeholder||Orthopedic Surgeon||Shriners of Northern California|
|Jennifer Lyman||Stakeholder||Founder||Cerebral Palsy Collaborative|
|Nancy Murphy, MD||Stakeholder||Director, Complex Care||Primary Childrens Hospital|
|Robert Sawin, MD||Stakeholder||Surgeon-in-chief||Seattle Childrens|
|Michele Shusterman||Stakeholder and Parent||Founder||CP Daily LivingCP NOW Foundation|
|Lisa Thornton, MD||Stakeholder||Physiatrist||University of Chicago|
|Ann Tilton, MD||Stakeholder||Pediatric Neurologist||Children’s Hospital New Orleans Louisana|
|Marion “Jack” Walker, MD||Stakeholder||Pediatric Neurosurgeon||Retired University of Utah|
|Brad Wilson||Stakeholder||CEO||Blue Cross Blue Shield of North Carolina|