IMPACCT: Infrastructure for Musculoskeletal Paediatric Acute Care Clinical Trials
Grant Recipient: Joseph A. Janicki, MD
Co-Investigators: Andrew Howard, MD; James G. Wright, MD
- Ann & Robert Lurie Children's Hospital, Chicago
- Presentations & Publications:
There have been no peer reviewed presentations. We have had presentations given at two meetings attended by society members regarding the resources we are developing to promote RCTs in pediatric orthopaedics.
None yet. We plan to publish treatment variation results from surveys of the POSNA membership on the topic questions of interest above as well as the summary from our Consensus Conference.
- Further Funding:
- Internal funding has been awarded by Lurie Children’s Hospital to further support the initiatives of this grant. We are planning to apply for federal funding during the summer of 2018.
- Additional Information:
- IMPACCT decreases the barriers for high quality research: Pediatric orthopaedics is relatively inexperienced with clinical research at high levels of evidence. Barriers to completing high-quality trials include low numbers of patients with specific diagnoses at a single site, few surgeons with experience in multicenter study administration, and a lack of site infrastructure to collect comprehensive data and to follow subjects. Randomized clinical trials (RCTs) require administrative overhead including regulatory compliance, data monitoring, contract negotiation, protocol development, and funding submission. The IMPACCT consortium seeks to answer questions in pediatric orthopaedics by conducting multicenter RCTs. A consortium would reduce current barriers by building infrastructure and experience. IMPACCT is led by three surgeon scientists (JAJ, JGW, AWH) with expertise in clinical research and success with conducting multicenter clinical trials. In addition, the administrative lead (JKB) is a PhD investigator with extensive experience in clinical research and leading multicenter consortiums. IMPACCT has recruited sites from POSNA who have extensive experience in treating pediatric fractures.
Process and activities to determine topics: In 2015, POSNA awarded a Clinical Trial Planning Grant in support of the IMPACCT initiative. With this funding, we hosted a meeting which included the society presidents of POSNA, the European Pediatric Orthopaedic Society, and the British Society for Children’s Orthopaedic Surgery. Here, the IMPACCT initiative gained endorsement and support while receiving feedback. A Consensus Conference followed in October 2017 where representatives from 32 sites across North America representing 288 surgeons convened to determine study priorities. At this conference, protocols were discussed, methodology was refined, and outcomes decided. At this conference, topics were scored from 1-5 (5 highest) based on significance, protocol, willingness to randomize, outcomes, and overall impact. Overall scores for fractures were medial epicondyle (MEF)(4.4), distal radius (DRF)(3.9), distal tibia fractures(3.6), tibial spine fractures(3.4), femur fractures(2.4) and lateral condyle fractures(3.6). MEF (1.3) and DRF (2.4) also scored highest when ranked (1 being highest, 6 being the lowest) in terms of priority. Surgeons also expressed a high willingness to randomize patients for these questions. Based on these results, we decided to seek funding for projects on MEF and DEF.
POSNA membership survey results: IMPACCT received surveys from 240 POSNA member surgeons during the spring of 2018 and confirmed that they have no consensus on the preferred way to treat MEF and DRF. When given displaced MEF scenarios, surgeons chose operative management 42-53% of the time and cast management 47-58%. More importantly, about 60% of respondents were willing to randomize. When given multiple displaced metaphyseal DRF cases, there was again wide practice variation in which surgeons recommended a reduction with rates varying from 52-98% depending on age. Surgeons were also willing to randomize DRF treatment in 51-74% of cases. Thus, randomization for both DRF and MEF trials is ethically justified by the fact that there is clinical equipoise and wide variation in treatment.
Collaboration with United Kingdom Investigators: The National Institute for Health Research Health Technology Appraisal (NIHR HTA) in the United Kingdom has prioritized Children’s Research in orthopaedics. The most important questions were assessed by NIHR commissioners and the clinical need was independently ratified by NIHR with MEF and DRF receiving priority scores of 4.0 and 3.5 (5 point scale). James Wright, Dan Perry, and their team were awarded a £1,200,000 grant to fund a randomized clinical trial comparing the operative and non-operative management of MEF beginning in fall 2018. IMPACCT is in close collaboration with the UK team with Dr. Wright being a Co-Investigator of IMPACCT and Mr. Perry a member of the IMPACCT’s Steering Committee. IMPACCT and the UK team have worked together to collaborate the trial protocols including inclusion criteria and outcome measures. The UK trial differs substantially from the North American setting with 100% of children covered by a national health insurance scheme. The patients, population, geography, hospital settings, and practitioners delivering care are sufficiently distinct that a UK only study is unlikely to have much influence on North America practice. This trial will allow confirmation of results in different enough settings that reinforcing trials would create a strong impetus for policy and practice change.
NIH Support for Trial Preparation: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has provided funding (1R34AR075303) from 7/19 to 12/20 to develop the RCT infrastructure, recruit sites, finalize protocols, complete trial docments and submit the U01 grant to perform IMPACCT’s clinical trials.
Justification for Clinical Trials: The management of two common upper extremity injuries, pediatric medial epicondyle fractures (MEF) and displaced distal radius fractures (DRF), is controversial with high practice variation. The debate largely focusses on whether to reduce these injuries to restore their usual position or to allow the fractures to heal in their injured position with simple immobilization. Observational studies support both reduction and simple immobilization for MEF and DRF. In both injuries, there have been few prospective and no randomized studies evaluating their treatment. Given the widespread variation in practice, children are either undergoing unnecessary procedures and anesthetic events when surgeons opt for reduction under anesthesia/ conscious sedation OR are being undertreated by simple immobilization. Both scenarios are unacceptable in that children face either anesthetic risks and extra costs or poor alignment with potential long term functional disability
Clinical Trial Summary: A multicenter randomized superiority trial of children with MEF and DRF is required to evaluate the clinical effectiveness of reduction under anesthesia/sedation vs. simple immobilization. The central hypothesis of this proposal is that children treated with reduction under general anesthesia (MEF) or conscious sedation (DRF) will have higher patient reported outcome scores compared to those treated with simple immobilization alone. Trials on both fractures will be conducted simultaneously to take advantage of the economy of scale and are similar in terms of anatomic location, outcome measures, and whether an intervention is necessary. Centers have agreed to recruit, randomize and treat patients according to the pragmatic protocol to obtain the 668 subjects necessary using a primary outcome of PROMIS at 12 months post injury. Secondary outcomes will compare additional patient reported outcomes scores, complication rates, and radiographic bone healing. Investigators have partnered with the Trial Innovation Network to increase the efficiency of trial development and execution.
The Scientific Aims of this application will challenge existing clinical practice for these two fractures:
Sites: Lurie Children’s Hospital, Boston Children’s Hospital, Children's Hospital Colorado, Children's Hospital Los Angeles, Children's Hospital of Philadelphia, Cincinnati Children's Hospital, Gillette Children's Hospital (Saint Paul), Children's Hospitals and Clinics of Minnesota (Minneapolis), Hospital for Special Surgery (NY), IWK Halifax, Johns Hopkins, Montefiore Medical Center, Nationwide Children's Hospital, Nemours/duPont Hospital for Children, Phoenix Children's Hospital, Rainbow Babies Hospital, Riley Children's Hospital, Hospital for Sick Children (Toronto, ON), Stanford University, Children’s Hospital Dallas, Texas Children's Hospital, UCLA Health, University of Iowa, University of Mississippi, University of New Mexico, New Orleans, Brown, Oregon Health and Science University, NYU Langone Children’s Hospital, Janet Weis Children’s Hospital/Geisinger, University of North Carolina, Rutgers University.
- IMPACCT-MEF: Determine if functional outcome scores (PROMIS) in operatively reduced medial epicondyle fractures are higher, compared to those treated simple immobilization.
- IMPACCT-DRF: Determine if functional outcome scores (PROMIS) of completely displaced distal radius fracture are higher with sedated reduction compared to those treated with non-sedated simple immobilization.
Future Directions: Subjects from this study will be followed at 2- and 3-year post injury time points to ensure that there are no long-term effects associated with the injuries or treatments. The experience and trial infrastructure created through these studies will enable IMPACCT to answer future questions in pediatric orthopaedics. We will host the next IMPACCT Consensus Conference to reengage the community, to identify the next questions to be answered and restart the IMPACCT process. We expect this process to be generalizable through the TIN and serve as an example for other surgical specialties. The completion of these trials will provide a framework, infrastructure and experience for future prospective multicenter clinical trials in pediatric orthopaedics as its results guide clinical decision-making.