SPORT has three specific aims:
- To simultaneously conduct three multi-center randomized controlled trials (RCT) comparing surgical and non-surgical treatment for patients with IDH, SpS or DS that are considered eligible for surgery with repeated longitudinal measurement up to 24 months.
- To characterize subjects who decline participation in the RCT but agree to be followed as part of an observational cohort. For these subjects we record all treatments, outcomes, and costs.
- To formally estimate the cost-effectiveness of surgical versus non-surgical interventions for IDH, SpS and DS through a synthesis of the results from the RCT and the observational study cohorts.
The 11 clinical centers that recruit patients into SPORT include: Dartmouth-Hitchcock Medical Center, Hanover, NH; Rothman Institute at Thomas Jefferson Hospital, Philadelphia, PA; Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL; Emory University Medical Center, Decatur, GA; University Hospitals of Cleveland/Case-Western Reserve, Cleveland, OH; New York University/Hospital for Joint Diseases, New York, NY; William Beaumont Hospital, Royal Oak, MI; University of California Medical Center-San Francisco, San Francisco, CA; Washington University Medical Center, St. Louis, MO; Nebraska Foundation for Spinal Research, Omaha, NE; and the Hospital for Special Surgery, New York, NY. Each of these sites is a member of the National Spine Network. This non-profit organization was formed in 1994 to develop and foster high quality and cost-effective care for its member’s patients. To this end, the organization developed an infrastructure for collecting outcomes data and a registry of patients with spinal conditions that provided the pilot data for the SPORT proposal.
SPORT inclusion () and exclusion criteria were developed from evidence-based management algorithms produced by the Agency For Health Care Policy and Research1
as well as by consensus of the participating physicians.
Inclusion Criteria by Diagnosis
For IDH, patients are eligible for SPORT if they have radicular pain and evidence of nerve root compression with a positive nerve root tension sign (positive straight leg raise test or femoral tension sign). Alternatively, they may have a reflex (asymmetric depressed reflex), sensory (asymmetric decreased sensation in a dermatomal distribution), or motor (asymmetric weakness in a myotomal distribution) deficit with associated radicular symptoms and positive nerve root tension signs. In addition, a confirmatory imaging study (MRI or CT) must indicate an intervertebral disc herniation (a protrusion, extrusion, or sequestered fragment) at a location (level and side) corresponding with the patient’s radicular signs or symptoms.20
Patients with only a bulging disc (circumferential symmetric extension beyond the interspace) are not eligible.20
Patients are eligible for the SpS trial in SPORT if they have pseudoclaudication (pain in the buttock, thigh, or leg on ambulation that improves with rest) or radicular pain with an associated neurologic deficit. The patient with suspected pseudoclaudication must have strong distal pulses or other testing to rule out vascular claudication. In addition, SpS patients must have a confirmatory imaging study (MRI or CT) showing lumbar spinal stenosis at one or more levels (L2 to sacrum) defined as narrowing of the central spinal canal, lateral recesses, or neural foramina due to encroachment on the neural structures by the surrounding bone and soft tissue. Patients are not eligible if they have evidence of instability on lateral flexion/extension radiographs, defined as a change of greater than 10° of angulation of adjacent segments by Cobb measurement or a change of more than 4 mm of AP or PA translation.
To be eligible for the DS trial in SPORT patients must have pseudoclaudication or radicular pain with an associated neurologic deficit and have a confirmatory imaging study (MRI or CT) indicating spinal stenosis at the L3-4 or L4-5 level and a degenerative forward slippage (of the L3 relative to the L4 vertebral body or the L4 vertebral body relative to the L5 vertebral body) in the sagittal plane on lateral standing radiograph. Displacement is usually less than or equal to 25% of the vertebral body. Patients with adjacent levels of stenosis are eligible (additional levels of stenosis are acceptable at L2-3 and/or L4-5 for degenerative slips at L3-4 and at L3-4 and/or L5-S1 for degenerative slips at L4-5).
Patients in all three diagnostic categories are not eligible for SPORT if they have any of the following exclusion criteria:
- insufficient trial of non-surgical treatment (6 weeks for IDH and 12 weeks for SpS or DS);
- cauda equina syndrome or progressive neurologic deficit requiring urgent surgery;
- overall health that makes spine surgery too life threatening to be appropriate;
- dramatic improvement with non-surgical care;
- possible pregnancy;
- active malignancy (patients with a history of any invasive malignancy except for non-melanoma skin cancer must have been treated with curative intent and have been free from clinical signs and symptoms of the malignancy for at least 5 years);
- a current fracture, infection, or significant deformity (greater than 15° lumbar scoliosis) of the spine;
- less than 18 years of age;
- prior lumbar spine surgery;
- current enrollment in another experimental spine-related protocol; or
- not available for follow-up or unable to complete questionnaires.
Recruitment and Enrollment
A research nurse and the participating physicians at each site identify potential subjects from among their clinic’s patients. In addition, SPORT has been advertised on a national level via press releases issued by the NIH/NIAMS and through guest speaking appearances by the principal investigator at various specialty society meetings. The participating clinical sites have advertised the project on a local level via print, television, and radio media. SPORT is also publicized on the NIH/NIAMS web site and on its own web site at http://sport.dartmouth.edu/nsn
Videotapes are used as part of the recruitment process to standardize and make available information that potential subjects need to make an informed decision about participation. Evidence-based programs produced by the Foundation For Informed Decision Making, “Treatment Choices For Low Back Pain: Herniated Disc” and “Treatment Choices For Low Back Pain: Spinal Stenosis” were edited to include information about SPORT. The programs provide information from the published literature regarding what currently is and is not known about the risks and benefits of the various treatment options for these conditions in lay language.
Informed consent is obtained from patients who are willing and eligible to participate. Data regarding demographic characteristics, medical history and comorbidities, symptoms (bothersomeness and frequency), and baseline measurements for all outcomes are obtained via a combination of patient interview, patient self-administered survey, and physician survey. All data is collected via portable computers that are equipped with software for touch screen data entry or via a SPORT internet site developed for this project.
The Randomized Trials
Patients who agree to participate in a randomized arm of the trial receive their treatment assignment at the time of enrollment. To assure that the number of subjects is approximately the same in the surgical and non-surgical groups for each site/disease group combination at the end of accrual, with approximately balanced assignment totals at interim intervals as well, a variable blocked randomization scheme is used.21
“Blocked” randomization means that treatment assignment is performed sequentially within blocks of a predetermined size so that when a blocked sequence is completed it will contain nearly equal numbers from each treatment group. “Variably blocked” means that the sequence and size of the blocks is varied randomly to further assure that the treatment assignments can not be predicted or manipulated.
An automated randomization system was created by the Statistical Center for SPORT based on computer generated, random, blocked treatment assignments for each disease group within each site. The treatment assignment tables are accessed through either a Web site maintained by the Statistical Center or through portable computers provided for each site with special software for administering questionnaires. When eligibility criteria have been verified, the program extracts the next randomization code from the appropriate disease sequence along with the sequence number and a confirmation code. These codes are permanently embedded in the patient record along with the exact time of randomization. Automated reports for enrollments are updated on demand through the secured Statistical Center Web sites and allow coordinators and investigators to track enrollment performance on a daily basis.
The Observational Cohorts
Patients may choose not to be randomized, but still be part of the study by participating in the observational cohort study. The inclusion and exclusion criteria, study intervention protocols, follow-up schedule, and study endpoints are identical to patients in the randomized study, but treatment is not randomly assigned.
The participating physicians have agreed to use the following standardized surgical approaches by diagnosis:
- IDH Decompression of the involved nerve root by a standard open or micro- discectomy;
- SpS Standard posterior decompressive laminectomy;
- DS Standard posterior decompressive laminectomy with or without an additional bilateral single level fusion (autogenous iliac crest bone grafting at the level of the listhesis with or without posterior instrumentation using pedicle screws).
In addition, participating physicians agreed to forego the use of any experimental devices or biologics as part of these procedures. However, if the physician decides during the surgery that the patient requires a procedure that differs from these protocols, he or she is instructed to perform that preferred procedure and record the details.
At a minimum, patients in all three diagnostic groups receive active physical therapy, education/counseling with home exercise instruction and a non-steroidal anti-inflammatory drug (NSAID) if tolerated. Patients may receive any additional non-surgical therapies deemed appropriate by their physician with all prescribed therapies recorded. Participating sites are encouraged to aggressively utilize all appropriate non-surgical therapies in those non-surgical patients who do not respond to the minimum intervention.
A complete list of non-surgical therapies being tracked in SPORT is shown in and . These lists are meant to include both typical treatments that would be prescribed by the participating physician as well as treatments patients might seek on their own. This approach, as opposed to a more limited, standardized non-surgical intervention in all patients, is more generalizable and will allow for a better understanding of the broad range of interventions, and their associated costs, being used in the care of patients with these diagnoses.
Follow-up data is gathered at two short-term follow-up intervals and five long-term follow-up intervals. The short-term follow-ups are at 6 weeks and 3 months from the time of treatment onset (surgery for the surgical group and the start of non-surgical therapy, generally at the time of enrollment, for the non-surgical group). The difference in timing the short term follow-up visits for the surgical and non-surgical treatment groups was necessitated by wide variability in the amount of time between randomization and surgical treatment. This occurs for a variety of reasons including surgeons’ schedules and case review for insurance and workers compensation. A complex set of follow-up timing rules have been developed to address potential biases that this might create that in some cases requires additional follow-up visits for surgical patients.
Long term follow-up occurs at 6 months, 12 months, and 24 months, and, if time permits, at 36 months and 48 months from the time of enrollment. One-hour clinic visits with the nurse coordinator are scheduled for all follow-ups. When study visits correspond to routine clinical care visits, the meeting with the nurse coordinator is in addition to the usual time scheduled with their physicians. When study visits occur outside the usual care, if possible the patient is also scheduled to meet with their physician at the beginning of this appointment for a brief visit.
The primary outcome measure for the SPORT project is health-related quality of life as measured using both generic and disease-specific instruments. Secondary endpoints, which are included to address the cost-effectiveness of surgical versus non-surgical treatment, include preference-based measures of current health, resource utilization, and work status.
Primary Outcomes SF-36 Health Status Questionnaire
We chose as our generic health status measure the SF-36 Health Status Questionnaire.48
This instrument consists of 36 questions that can be aggregated to form 8 sub-scales (physical function; mental health; general health perceptions; pain; role limitations-physical; role limitations-emotional; social functioning; and vitality) and two summary scales (physical and mental component scales). On each scale, higher scores indicate better outcomes. Scores can be compared to published age- and sex-matched general population or disease-specific norms.
Oswestry Disability Index
For our disease-specific instrument we chose the Oswestry Disability Index.19
We are using a version of the questionnaire that consists of nine questions relating to limitations in performing the following activities during the past week: getting dressed, lifting, walking and running, sitting, standing, sleeping, social and recreational activities, traveling, and sexual activity. Each question has six graded responses that range from unlimited, pain free activity to total incapacity due to pain. The sum of the 9 responses is expressed as a percentage of the maximum score. In the original scoring of the instrument higher scores represented greater disability.19
We reverse the coding of the responses so that higher scores indicate better outcomes for consistency with the interpretation of the SF-36 measures.
Secondary Outcomes Preference-based Measures of Current Health
To assess the economic value of low back pain treatment we use quality-adjusted life years (QALYs) as our measure of effectiveness. To estimate QALYs, preference-based measures (i.e., utilities) for current health are required. Utility values,40,44
that range from 0 (worst imaginable health) to 1 (best imaginable health) reflect the desirability of health outcomes. Utilities are important to consider because patients with the same degree of functional limitation or symptoms may feel very differently about life under those circumstances.37
In SPORT, utility for current health is estimated using two preference classification systems—the 5-item EuroQoL EQ-5D.5
and the15-item Health Utilities Index (HUI).47
Both provide societal utility values that are appropriate for estimating QALYs. In addition, we obtain individual patient values for current health using a visual analogue scale (VAS).5
Resource Utilization and Cost
In our analysis, we distinguish among direct inpatient costs, direct outpatient costs, and indirect costs. To estimate costs associated with surgical and non-surgical care, we track resource utilization and work status at each follow-up period. The patient is our primary source for resource utilization and work history data. To enhance the quality of the recalled cost data, two approaches are employed. First, we provide all patients with detailed diaries, which serve as memory aids, for tracking encounters with health care providers. Second, we minimize the period of recall. To capture costs for the first 3 months of study enrollment, cost data are obtained at 6 weeks and 3 months using a 6-week recall window. At the 6, 12, 24, 36 and 48 month visits, we record most costs using a one-month recall period and use it to estimate average costs for the months between visits. However, certain costs, including hospitalizations and medical devices, are captured for the entire period between study visits.
1. Direct Inpatient Costs
To identify resource use associated with hospitalization, patients are questioned at follow-up visits about hospitalizations since their last study visit. Inpatient services include both physician and hospital service components of costs for each of the hospital stays experienced during the period of follow-up. Additional costs incurred during hospitalization include physician and diagnostic service expenses. We estimate costs for these using the Resource-Based Relative Value Scale (RBRVS),24
which is used by the Centers for Medicare and Medicaid Services.7
We favor this approach over using institution and cost-center-specific cost-to-charge ratios because it reflects national fee schedules and can therefore be generalized to the US population.
2. Direct Outpatient Costs
To identify care other than hospitalization, patients are questioned at each follow-up visit about their use of outpatient services, medications, and devices. We collect the relevant physician costs for outpatient services using the same RVU weights as for the physician inpatient services. To estimate costs of medications and other health care services not covered by Medicare, we are surveying providers on charges for services at diverse geographic locations involved in this study. Cost estimates of physical therapy at each site are derived based on condition-specific profiles, which are being developed through surveys of each site’s physical therapy practices.
3. Indirect Costs
An important component of the overall economic evaluation of surgical and non-surgical treatment for these conditions is the measurement of indirect costs of employees, employers, and the government resulting from the spine-related condition. To this end, our survey asks about occupation, difficulty performing work (either in a job or as a homemaker), job changes, and financial distress stemming from the spine condition. To estimate indirect costs associated with time lost from work, we collect earning and wage information at baseline to allow for assigning costs to lost work hours. Average weekly hours are collected at each study visit, while wage, insurance coverage, disability payments, and measures of difficulty working are collected at 6 months, 12 months, and yearly thereafter. Finally, we collect information about factors such as insurance status, disability payments, and income of other family members to determine what factors affect labor force participation and treatment options. We use the pre-treatment wage rate in these calculations, but also include a question at the 12-month follow-up regarding the post-treatment wage rate.
A monitored event form is completed whenever it is learned that a study patient has been lost to follow-up, has crossed over from their randomly assigned or self-designated treatment group, or has withdrawn from the study. Deaths and hospitalizations are immediately reported to the study Principal Investigator, Data and Safety Monitoring Board, the NIAMS Project Officer, and all participating IRB’s. The Data and Safety Monitoring Board uses narrative data provided by the site regarding the circumstances of the event as well as any documentation in the medical record, discharge or operative notes, or death certificates to determine whether the event was related to the patient’s spine condition or its treatment. All other medical complications are monitored throughout the study at all routine follow-ups and are reported to the Data Safety Monitoring Board and the NIAMS Project Officer at regular intervals. IRB notification guidelines are followed according to each site’s specifications as well as complying with national regulations (45CFR46, see http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm)
Any deviation from the study protocol is considered a protocol violation. Major protocol violations include: randomization of an ineligible patient; enrollment of a SPORT participant in any other spine-related study; subject receiving the wrong treatment; randomization prior to completion of necessary paperwork or diagnostic studies; loss of radiology or operative report; and informed consent violations. Minor protocol violations include failure to report a monitored event within 24 hours of learning of it and failure to obtain follow-up data within the specified time intervals. Violations are reviewed weekly and serve as data for reports to the DSMB, NIAMS and IRB’s.