31 The Development and Evolution of the Harms Study Group Registry


 

Michelle C. Marks, Maty Petcharaporn, Peter O. Newton, Randal R. Betz, and Harry L. Shufflebarger


Summary


In this chapter, the history and evolution of the Harms Study Group, a multicenter research collaborative, are highlighted. The initial formation of the group and the preliminary surgical outcomes study are described to assist groups now and in the future in planning and implementing multicenter research efforts. The strategies employed to develop formal study procedures and processes (from surgeon membership guidelines to data collection standardization manuals) and ultimately the creation of a central infrastructure are shared. Upholding the “gold standard” in multicenter research has been a priority for the Harms Study Group, and methods and mechanisms to continually meet this standard are described. Some key elements of the Harms Study Group’s success include the establishment of an executive committee to strategically plan research initiatives and maintaining the highest standards for prospective data collection. In addition, collaborative generation of study ideas, their execution, and eventual publishing in peer-reviewed journals have helped change the way children with spine deformities are treated. Surgeon performance dashboards have improved surgical quality across centers and serve as a valuable tool for surgeons to evaluate and improve their outcomes. The progression of the group, from a collaborative group of surgeons to a formal nonprofit entity, reveals the ability to grow an organization to expand the positive impact from the research conducted. In particular, patient education is a primary goal and has been promoted through both patient-oriented education handbooks and videos and via annual educational courses.




31 The Development and Evolution of the Harms Study Group Registry



31.1 Introduction


The Harms Study Group (HSG) is a multicenter research organization focused on prospective research in spinal deformities. The group has been in existence since 1995 and has produced substantial research on the outcomes of scoliosis treatment. Information on the development and evolution of this group and its prospective registry studies is shared here to assist others interested in performing multicenter research and/or forming a research study group.



31.2 Development of a Study Group


The HSG was initiated in 1995, as a small group of collaborative surgeons came together under the coordinated leadership of Dr. Randal Betz and Prof. Juergen Harms (Fig. 31‑1). The initial objective of the group was to evaluate the outcomes of the anterior surgical approach for thoracic adolescent idiopathic scoliosis (AIS) popularized by Professor Harms in comparison to the posterior approach that was the standard. The initial publications from the group’s efforts, many penned by Dr. Betz, documented the early outcomes of the anterior approach. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9

Fig. 31.1 Randal Betz, MD, and Prof. Juergen Harms, founding members of the Harms Study Group.

Initially comprising only six surgeons (Juergen Harms, Randal Betz, David Clements, Harry Shufflebarger, Larry Lenke, and Tom Lowe), the original group members dedicated their energy, focus, and expertise to collect the necessary data to compare outcomes of the newly developed anterior approach relative to the established posterior methods (Fig. 31‑2). The group was named after Juergen Harms (Fig. 31‑3) in honor of the contributions he made to the development of the anterior procedure.

Fig. 31.2 Early Harms Study Group meeting circa 2000.
Fig. 31.3 The Harms Study Group is named in honor of Professor Juergen Harms.

The initial funding for this multicenter effort was provided as a seed grant from Mr. Lutz Biedermann, of Biedermann Motech, Inc. Subsequently, the funding came from grant monies from DePuy Spine. In 2014, the group started receiving grant monies from other industry partners, which now, in addition to DePuy Synthes Spine, include Stryker-K2M, Medtronic, EOS Imaging, Zimmer-Biomet, NuVasive and the Food and Drug Administration (FDA)..


The small initial research focus for the group was a successful strategy, as the data capture was realistic and feasible. The original primary outcome variables were radiographic measures—primarily coronal Cobb correction, compensatory curve correction, and kyphosis restoration. In the very first meeting, it was determined that the current classification system at that time of King et al was not adequate to allow comparison of outcomes. It was through the comprehensive radiographic evaluation utilized in this study group and through the large dataset accomplished through the multicenter data collection effort that the Lenke classification was developed and established 10 , 11 , 12 (Fig. 31‑4).

Fig. 31.4 The Lenke Classification System, developed through the efforts of the Harms Study Group.

As the surgeon investigators of the study group met on a regular basis in the early years, the radiographic measures were further developed and the radiographic analysis became very detailed, with over 25 coronal radiographic measures and 20 lateral radiographic measures. Randy Betz and Larry Lenke were primarily responsible for the development of this comprehensive radiographic analysis, which would later be published. 36

Fig. 31.5 The Harms Study Group Executive Committee. Left to right: David Clements, MD, Michelle Marks, PT, MA, Randal Betz, MD, Harry Shufflebarger, MD, Amer Samdani, MD, and Peter Newton, MD.

The initial momentum of the group was robust. Additional surgeons were invited to participate in the effort and thus the data quantity increased. As the data volume grew, the research capacity and focus were able to expand. A Natural History cohort was also added, capturing patients who were offered surgery but elected nonoperative care and are followed at the same intervals. Another major contribution to the scientific literature from the early efforts of this group and the early multicenter data was the development of the Scoliosis Research Society-24 (SRS-24) Questionnaire, a health-related quality-of-life assessment tool. 13 , 14


In the early stages of the group’s development, an executive committee (EC) was established to govern the group. It was (and still is) comprised of five surgeon members (three founding members and two younger surgeon leaders) and the director of the study group (Fig. 31‑5).

Fig. 31.6 Ed Crowe, 2005 vice president of Marketing for DePuy Spine and enthusiast of the Harms Study Group.

The EC members function as a liaison with industry colleagues, initiating and negotiating proposals for funding to support the group’s research. The EC assisted in developing the group’s strategic plan. This 3- to 5-year plan defines the scope of work for the group and focuses the research on relevant and important clinical questions. The strategic plan identifies the potential funding sources and opportunities to ensure that the group’s research is funded and maintains the critical resources to ensure the continuation of the research productivity and contributions from the group.


The prospective AIS database registry grew into the largest prospective cohort in existence for this patient population. In 2005, the study group celebrated its 10-year anniversary and Ed Crowe, the VP of Marketing for DePuy, provided the following sentiments for the group (Fig. 31‑6):


“‘A Note from Ed Crowe 1/2/06’:
Fig. 31.7 The Harms Study Group/Setting Scoliosis Straight central infrastructure team in 2017, located in San Diego.

The growing strength of the HSG over the last several years always impressed me. The Executive Committee superbly organized the study group with standards and bylaws; the reinvigorated study group members charged the intellectual atmosphere; the entire group remained vital through the commitment to complete clinical studies and publish frequently. The last ten years and especially the last few years have demonstrated just how beautifully a well-run group operates. I am certain you are proud of your accomplishments as you should be. The HSG will no doubt drive new thinking and better clinical care for years to come. Ironically, for me, the best part of that great group is each fine individual in the HSG. A room full of HSG members is full of people whom I respect and people whom I view as my friends. That reality made the whole enterprise something personal to me. The opportunity to work, to talk, and to laugh with HSG members was a rare, outstanding deal. I think of the 10th anniversary of the HSG as a triumph of some very good human beings, people I like very much.”


The EC is also responsible for developing and implementing the group’s membership guidelines. In order to ensure a productive and collaborative membership, a document of guidelines was established to define the criteria for maintenance of membership in the group. This document defines the expectations of participating sites and their role in contributions to the multicenter research registry through high-quality data submissions. It also defined the expectations of surgeon members with regard to research productivity such as research abstract submission for presentation at international scientific meetings and manuscripts submitted for publication in peer-reviewed journals. Key within the guidelines were standards for authorship of multicenter papers that have evolved to mirror those of the International Committee of Medical Journal Editors (ICMJE).


In addition, the EC was instrumental in establishing the central infrastructure for the study group. The central infrastructure (currently a team of 15 employees) was developed to perform the functions of a contracted research organization (CRO): processing the data from the participating sites; establishing research funding agreements (RFAs) and data use agreements (DUAs); collaborating, negotiating, and contracting with industry for research study funding; monitoring site institutional review board (IRB) compliance and informed consenting compliance; and performing data reimbursements for all participating sites. In addition, the central infrastructure is responsible for submitting research funding proposal to industry, research societies, and research and private foundations. The core infrastructure manages the funding for the study group and ensures compliance in all tax reporting (Fig. 31‑7 and Fig. 31‑8).

Fig. 31.8 Michelle Marks, PT, MA, and Maty Petcharaporn, BS, both serving the Harms Study Group and Setting Scoliosis Straight Foundation for over 20 years.
Fig. 31.9 (a, b) 3D reconstructions of adolescent idiopathic scoliosis radiographic images (posteroanterior and lateral views).

Processing the research outcomes data has evolved into a structured quarterly process involving central radiographic image acquisition and storage on a central server. These large high-quality image files are cataloged and accessed by the central infrastructure team for two-dimensional (2D) radiographic measurements and three-dimensional (3D) reconstructions. The measurements are calculated and uploaded into the central database (Fig. 31‑9).


Data quality assurance (QA) measures are performed (discussed in detail later), and all data are verified centrally by the core research staff before use in data queries or study analyses. An important function of the central infrastructure team is to ensure the standardization of data collection across the many sites of the study group. This uniform methodology is documented and communicated to the sites through data collection standardization manuals for each prospective study. Additionally, each new study site coordinator receives individualized training to ensure standardization of the work.



31.3 Database Evolution


The database structure and function of a research registry were integral to the study group’s success. In 1994, the HSG created a database to store data collected on patients diagnosed with AIS. The initial database, built-in FoxPro code, eventually contained data on over 2,000 patients collected from sites across the world including the United States, Canada, and Germany.


In 2001, the database was upgraded to a Microsoft SQL server platform. This allowed for web-based accessibility, giving site coordinators the opportunity to contribute data remotely and in real-time. Due to the amount of data stored and being captured across all sites, a query tool was implemented into the design to allow for ease of data reporting. The query tool allowed for bulk data extraction as well as the ability to filter data based on specific variables (Fig. 31‑10).

Fig. 31.10 The Harms Study Group database query tool interface.

With the growth of the AIS studies came the need to collect additional clinical outcome variables. Database modifications to accommodate these changes proved to be onerous and costly endeavors, so the HSG set forth on its third upgrade to the database, one that allowed for flexibility in the database layout. In 2009, the database was upgraded to give the ability to create and remove data variables as well as create new, complete databases specific to any new studies. From these enhancements, the database was restructured with a database-building tool that provided the immediate ability to expand and grow (Fig. 31‑11).

Fig. 31.11 The Harms Study Group database query tool interface.

The HSG has since implemented registries for multiple diagnostic patient populations with spinal deformities including cerebral palsy, Scheuermann kyphosis, and Marfan syndrome.


In 2018, the HSG database was further upgraded to increase functionality and data efficiency. The original database platform could only be accessed on a Windows operating system while using Internet Explorer as the web browser. This limited users who were functioning on different operating systems, as well as users who preferred alternative secure browsers (i.e., Google Chrome, Firefox, etc.). The database was modified to allow for access on all browsers as well as mobile devices. Mobile compatibility enhanced the ability to collect and enter data in clinic, as well as capturing patient’s health-related quality-of-life assessments. To date, many institutions have transitioned to electronic data capture through their electronic medical records (EMR) in order to reduce the amount of time necessary to collect study information and to reduce the amount of error associated with data entry. The database was modified with a pathway to auto upload these data into the current database increasing the efficiencies of data capture (Fig. 31‑12).

Fig. 31.12 The Harms Study Group database building tool interface.

Currently, the HSG database houses data for over 8,000 prospective and over 1,000 retrospective patients with multiple spinal deformity diagnoses that range from AIS to scoliosis in cerebral palsy. The HSG registry database will constantly be modified to meet the demands of future research and technological advances in order to advance the treatment outcomes of children with spinal deformities.



31.4 Research Study Development and Evolution


The first research study of the group was designed around a clinical aim of comparing the outcomes of two surgical approaches for the correction of AIS. It was created to capture many components of treatment (preoperative, perioperative, and postoperative care) at a granular level. Over the years, the initial AIS research study evolved from a 2-year endpoint study into an ongoing AIS outcomes registry, with a concerted effort to capture the longer-term follow-up (at the 5-, 10-, and now 20-year postoperative time points). Specific aims of the research registry were clearly defined to ensure that the data variables collected would answer specific clinical questions associated with each specific aim. Although the initial study was to compare the anterior open instrumentation and fusion approach to the posterior open fusion approach, this study design and adaptability of the study group provided the opportunity for a third approach (anterior thoracoscopic fusion and instrumentation) to be prospectively investigated. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22


While the prospective AIS registry study was underway, the group also undertook multiple retrospective investigations to use the collective power of the group. Examples include the outcomes of the use of traction in the treatment of severe spinal deformity. 23 the efficacy of hemivertebra resection for congenital scoliosis, 24 and the efficacy of spinal fusion and instrumentation in patients with cerebral palsy and scoliosis. 25 , 26 The retrospective study experience of cerebral palsy patients with scoliosis was used to design the prospective study entitled, “Prospective Database Registry Study of Scoliosis in Children with Cerebral Palsy.” 25 , 26 The retrospective effort provided insight into the feasibility of data capture, the expense analyses of site coordinator time, patient/procedure prevalence at participating sites, and the importance of a nonoperative comparative cohort. The study of scoliosis in cerebral palsy is the second prospective study currently enrolling patients within this multicenter study group. This study incorporated a comparative control cohort of patients choosing nonoperative management. This comprised a group of patients for whom surgery was recommended but who opted not to pursue surgery. This prospective cohort study design elevated the level of evidence of the study results. 27


Another retrospective study performed by this group that assisted in the development of a prospective study design was the multicenter retrospective study of spinal deformity correction in Scheuermann kyphosis. 28 The “Prospective Study of Scheuermann’s Kyphosis” was subsequently conducted for 12 years and resulted in numerous contributions to the literature. 28 , 29 , 30 , 31 , 32 , 33 , 34


Currently, the two multicenter prospective registries (AIS and Cerebral Palsy Scoliosis) enroll approximately 500 new patients per year, and over 2,000 patient visits are processed through the central infrastructure team annually. Each year, roughly 50 scientific abstracts are produced from these research data and shared with colleagues at international meetings, and approximately 20 manuscripts are published in peer-reviewed journals.



31.5 Surgeon/Site Participation


The study group has developed policies and procedures associated with the prospective research participation. Surgeon members at participating sites are invited to participate because they have an established research staff (site coordinators) and have shown research productivity in the past.


IRB approval for each registry study at each institution is attained by the local site coordinators and then housed centrally so the HSG infrastructure is able to track initial approval dates and annual IRB renewal agreements without lapses that impact data collection. No data are accepted into the central database until initial IRB approval is documented and annual renewals are in place prior to expiration. All protocol amendments and changes to case report forms and the standardization manuals are approved by respective IRBs and ethics boards on an ongoing basis. All data submitted to the central infrastructure are deidentified to protect patient privacy and health information. A Unique Patient Identifier (UPI) is assigned within the database structure, and each participating site maintains locally the list of study patient names with assigned UPIs.


Surgeon members of the HSG not only participate by submitting data to the group’s prospective database registries but also play the key role of asking the important clinical questions the group has the volume of data for statistical power to answer. This is a collaborative effort that occurs when the surgeons gather together at least twice annually. These meetings provide the opportunity to identify current knowledge gaps via a thorough review of the study data variables and review of the current submitted patient data. Proposed clinical questions are discussed as a group and surgeon member investigators are assigned to perform various individual analyses (“member projects”). The abstracts and manuscripts generated by this process are peer-reviewed by the group prior to submission for presentations and/or publication (Fig. 31‑13).

Fig. 31.13 The Harms Study Group Surgeon members and research coordinators gather at the HSG annual research meeting in 2017.


31.5.1 Data Quality Assurance



Ensuring Data Quality

The prospective studies are designed for local site data collection with central data QA checks. Each site contributes to the QA process through this methodology:




  • Each site has a research coordinator who is trained at the time of hire, both locally at the site and through training from the central infrastructure. Coordinators are given case report forms for each visit time point and data collection standardization manuals for each of the studies.



  • Consecutive enrollment tracking is performed by each site to ensure that all patients who meet the inclusion criteria are approached to be enrolled. This is designed to reduce the risk of inclusion bias.



  • Sites are given their data entry accuracy rate each quarter to track errors and improvements. These rates are benchmarked across sites.



  • On a quarterly basis, site coordinators are instructed to send a randomly selected deidentified patient source document to the HSG QA team to ensure quality of data entered into the database.


The central infrastructure is committed to QA and has put the following policies and procedures in place:




  • All deidentified radiographic images are obtained from the participating sites and measured centrally by trained staff. The inter-rater reliability of the measuring staff ranges from good to excellent.



  • QA guides including normative and predefined acceptable ranges for data variables and assessment of illogical data are in place.



  • Thorough review of all new data submitted is undertaken on a quarterly basis and any erroneous, illogical, or missing data are sent back to the site for evaluation and/or correction.



  • All new data entered are “unverified” until quality checked. Data that have not been verified are not included in any study analyses.



  • Each quarter, internal QA validation efforts are undertaken to assess the inter-rater reliability of the QA process.



  • Finally, a final QA is run when study analyses are performed. When the database is queried for specific study variables by the core infrastructure team, a central statistician analyzes the dataset for outliers and questionable data. Data validation requests are again sent back to the site to determine the accuracy.

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Apr 30, 2022 | Posted by in ORTHOPEDIC | Comments Off on 31 The Development and Evolution of the Harms Study Group Registry

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