<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02966639</url>
  </required_header>
  <id_info>
    <org_study_id>D16174</org_study_id>
    <nct_id>NCT02966639</nct_id>
  </id_info>
  <brief_title>Validation of Appropriateness Criteria for the Surgical Treatment of Lumbar Degenerative Spondylolisthesis</brief_title>
  <official_title>Validation of Appropriateness Criteria for the Surgical Treatment of Lumbar Degenerative Spondylolisthesis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dartmouth-Hitchcock Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of this study is the external validation of the appropriateness criteria&#xD;
      for the surgical treatment of Lumbar Degenerative Spondylolisthesis. We will assess,&#xD;
      prospectively, whether patients treated &quot;appropriately&quot; have better outcomes than those&#xD;
      treated &quot;inappropriately&quot; according to the RAND Appropriateness Method (RAM) Criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Spinal stenosis is the most common reason for lumbar surgery in patients over age 65, and a&#xD;
      substantial proportion of stenosis patients present with concomitant lumbar degenerative&#xD;
      spondylolisthesis (LDS). This condition is characterized by the anterior translation of a&#xD;
      vertebra due to degenerative changes in the facet joints and disk, most commonly at L4-L5,&#xD;
      and is most prevalent in women over age 50. The translation commonly results in spinal&#xD;
      stenosis, and patients tend to present with various combinations of low back pain,&#xD;
      radiculopathy, and neurogenic claudication. The Spine Patient Outcomes Research Trial (SPORT)&#xD;
      demonstrated better outcomes for patients treated with surgery compared to non-operative&#xD;
      treatment. However, all patients met strict inclusion criteria including the presence of&#xD;
      radicular pain or neurogenic claudication, cross-sectional imaging demonstrating spinal&#xD;
      stenosis consistent with their symptoms, and duration of symptoms for over three months.&#xD;
      Additionally, specific patient and disease characteristics were shown to significantly affect&#xD;
      surgical and non-operative outcomes. While the literature makes it clear that surgery results&#xD;
      in better outcomes than non-operative treatment for the &quot;average&quot; LDS patient, surgeons have&#xD;
      to help make treatment decisions for patients with a diverse array of characteristics that&#xD;
      can have positive and negative effects on surgical outcomes. Additionally, many LDS patients&#xD;
      do not meet the inclusion criteria of SPORT, and extrapolating the results to these patients&#xD;
      is inappropriate. The currently available evidence provides surgeons with some general&#xD;
      principles to help guide decision-making but does not inform decision-making at the&#xD;
      individual patient level.&#xD;
&#xD;
      Many studies have evaluated the effect of specific patient and disease characteristics on&#xD;
      surgical outcomes for spinal stenosis. These have generally shown worse surgical outcomes for&#xD;
      patients with medical and psychological comorbidities, lower socioeconomic status and&#xD;
      educational attainment, smokers, those with predominant back pain, those receiving workers'&#xD;
      compensation, and patients involved in litigation. However, subgroup analysis of the SPORT&#xD;
      degenerative spondylolisthesis cohort, the first study that evaluated predictors of both&#xD;
      surgical and non-operative LDS outcomes, demonstrated that these factors tended to predict&#xD;
      both worse surgical and non-operative outcomes. As a result, most of these subgroups tended&#xD;
      to have a similar treatment effect of surgery (i.e. relative advantage of surgical compared&#xD;
      to non-operative outcomes) even if their absolute degree of improvement with surgery was&#xD;
      less. While these data suggest that most LDS patients meeting the SPORT inclusion criteria&#xD;
      will improve more with surgery than with non-operative treatment, many LDS patients do not&#xD;
      meet the SPORT inclusion criteria, and evidence is needed to provide treatment guidelines for&#xD;
      these patients.&#xD;
&#xD;
      In an ideal world, randomized-controlled trials (RCT) would be performed for multiple&#xD;
      subgroups in order to compare outcomes among all available treatment options. The SPORT LDS&#xD;
      RCT demonstrated the difficulty in performing a seemingly straightforward RCT comparing&#xD;
      surgery to non-operative treatment, with only 64% of patients assigned to surgery having&#xD;
      undergone an operation within 2 years, and 49% of patients randomized to non-operative&#xD;
      treatment having undergone surgery by 2 years. Given that it is not possible to perform&#xD;
      sufficiently powered RCTs to compare surgical and non-operative outcomes for multiple LDS&#xD;
      subgroups, other methods must be considered to generate guidelines to help surgeons and LDS&#xD;
      patients select the most appropriate treatment based on their individual characteristics. One&#xD;
      such alternative is the RAND appropriateness method (RAM), which combines a detailed review&#xD;
      of the literature with a modified Delphi panel approach to create appropriateness criteria&#xD;
      based on collective expert opinion. A major strength of the RAM is that is involves a high&#xD;
      level of clinical detail, allowing for treatment recommendations to be made based on a number&#xD;
      of relevant patient and disease characteristics that can be applied to individual patients.&#xD;
      The RAM has been widely used and studied by several groups in various countries in relation&#xD;
      to different spinal problems. The RAM is considered most useful for procedures that are used&#xD;
      frequently, associated with a substantial amount of morbidity and/or mortality, consume&#xD;
      significant resources, have wide variation among geographic areas in rates of use, and whose&#xD;
      use is controversial. All these criteria apply to the procedures commonly used in the&#xD;
      surgical treatment of LDS. Depending on the definition of success, success rates at 1 year&#xD;
      after surgery range from 50% to 94%. The rate of lumbar fusion in the United States Medicare&#xD;
      population has been shown to vary nearly 20-fold across hospital referral regions. In the&#xD;
      SPORT LDS cohort, significant differences were found across different study centers in&#xD;
      patients' baseline neurological deficit, stenosis location and severity, and number of&#xD;
      stenotic levels as well as in their functional outcome out to 4 years after surgery. High&#xD;
      levels of geographic variation are frequently attributed to uncertainty about the most&#xD;
      appropriate treatment for a given condition, usually reflecting a lack of strong evidence.&#xD;
      Given the lack of treatment recommendations that can be applied at the individual LDS patient&#xD;
      level, an international group of experts were convened to use the RAM to create&#xD;
      appropriateness criteria for surgery for LDS.3&#xD;
&#xD;
      The RAM process included 14 experts from the USA, UK, Belgium, Sweden, Norway, Spain,&#xD;
      Switzerland, and Hungary with backgrounds in orthopaedic surgery, neurosurgery, rheumatology,&#xD;
      and physical medicine. The experts considered the appropriateness of decompression alone,&#xD;
      uninstrumented fusion with or without decompression, and instrumented fusion with or without&#xD;
      decompression for 744 patient scenarios. The variables defining the scenarios included&#xD;
      symptomatology (back pain, radicular pain, and/or neurogenic claudication), severity of&#xD;
      neurological deficit, presence of significant foraminal and/or central stenosis, level of&#xD;
      disability, presence of significant medical comorbidities, clinically relevant &quot;instability&quot;,&#xD;
      and the presence of significant psychosocial &quot;yellow flags&quot;. The appropriateness of each type&#xD;
      of surgery was rated on a 1-9 scale (1-3 inappropriate, 4-6 uncertain, and 7-9 appropriate)&#xD;
      in two separate rounds by the expert panel. Surgery of one type or another was considered&#xD;
      appropriate in 27% of scenarios, uncertain in 41%, and inappropriate in 31%. In general,&#xD;
      scenarios in which symptoms were limited to back pain in the absence of instability were&#xD;
      considered inappropriate for surgery, whereas the presence of radiculopathy or claudication,&#xD;
      neurologic deficit, and instability increased the likelihood of a scenario being considered&#xD;
      appropriate for surgery. The presence of medical comorbidities and &quot;yellow flags&quot; decreased&#xD;
      the likelihood of a scenario being considered appropriate for surgery. There was widespread&#xD;
      disagreement about the appropriate use of instrumentation, but, in general, fusion of some&#xD;
      variety was more likely to be considered appropriate in the presence of back pain or&#xD;
      instability.&#xD;
&#xD;
      The RAM was successfully employed to develop appropriateness criteria for LDS surgery. Prior&#xD;
      to widespread clinical implementation, the results need to be validated in the LDS&#xD;
      population. If validated successfully, a computer-based algorithm could be developed to help&#xD;
      surgeons and patients select treatment using the appropriateness criteria. This would&#xD;
      represent a significant advancement in shared decision making for LDS, effectively moving&#xD;
      from population-based recommendations to those that can be applied at the individual patient&#xD;
      level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Core Outcome Measures Index</measure>
    <time_frame>12-months Post-Treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oswestry Disability Index</measure>
    <time_frame>12-months Post-Treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Outcome of Treatment Questions</measure>
    <time_frame>12-months Post-Treatment</time_frame>
    <description>Questions with 5 response categories, dichotomized to &quot;good&quot; and &quot;poor&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction with Care</measure>
    <time_frame>12-months Post-Treatment</time_frame>
    <description>Questions with 5 response categories, dichotomized to &quot;good&quot; and &quot;poor&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications from Treatment</measure>
    <time_frame>12-months Post-Treatment</time_frame>
    <description>Questions with 5 response categories, dichotomized to &quot;good&quot; and &quot;poor&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Further Treatment after Initial Treatment</measure>
    <time_frame>12-months Post-Treatment</time_frame>
    <description>Questions with 5 response categories, dichotomized to &quot;good&quot; and &quot;poor&quot;</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">171</enrollment>
  <condition>Spondylolisthesis</condition>
  <arm_group>
    <arm_group_label>LDS Patients</arm_group_label>
    <description>All patients with a diagnosis of single-level Lumbar Degenerative Spondylolisthesis who present to the DHMC Spine Center.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Skeletally mature individuals with a primary pathology of single-level degenerative&#xD;
        spondylolisthesis in the lumbar region of the spine.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is the patient skeletally mature with a primary pathology of single level degenerative&#xD;
             spondylolisthesis in the lumbar region of the spine (with or without stenosis at other&#xD;
             levels)?&#xD;
&#xD;
          -  Able to give written informed consent&#xD;
&#xD;
          -  Patient has already undertaken a course of non-operative care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primarily degenerative scoliosis curvature greater than 15 degrees&#xD;
&#xD;
          -  Presence of Isthmic Spondylolisthesis&#xD;
&#xD;
          -  Cauda equine syndrome requiring immediate emergency surgery&#xD;
&#xD;
          -  Active spinal infection, tumor, or unhealed fracture&#xD;
&#xD;
          -  Inability to understand English&#xD;
&#xD;
          -  Patient refused to participate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adam M Pearson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth-Hitchcock Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>August 5, 2021</last_update_submitted>
  <last_update_submitted_qc>August 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>Adam M. Pearson</investigator_full_name>
    <investigator_title>Staff Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylolisthesis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02966639
org study id: D16174
nct id: NCT02966639
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of this study is the external validation of the appropriateness criteria
      for the surgical treatment of Lumbar Degenerative Spondylolisthesis. We will assess,
      prospectively, whether patients treated "appropriately" have better outcomes than those
      treated "inappropriately" according to the RAND Appropriateness Method (RAM) Criteria.
Spinal stenosis is the most common reason for lumbar surgery in patients over age 65, and a
      substantial proportion of stenosis patients present with concomitant lumbar degenerative
      spondylolisthesis (LDS). This condition is characterized by the anterior translation of a
      vertebra due to degenerative changes in the facet joints and disk, most commonly at L4-L5,
      and is most prevalent in women over age 50. The translation commonly results in spinal
      stenosis, and patients tend to present with various combinations of low back pain,
      radiculopathy, and neurogenic claudication. The Spine Patient Outcomes Research Trial (SPORT)
      demonstrated better outcomes for patients treated with surgery compared to non-operative
      treatment. However, all patients met strict inclusion criteria including the presence of
      radicular pain or neurogenic claudication, cross-sectional imaging demonstrating spinal
      stenosis consistent with their symptoms, and duration of symptoms for over three months.
      Additionally, specific patient and disease characteristics were shown to significantly affect
      surgical and non-operative outcomes. While the literature makes it clear that surgery results
      in better outcomes than non-operative treatment for the "average" LDS patient, surgeons have
      to help make treatment decisions for patients with a diverse array of characteristics that
      can have positive and negative effects on surgical outcomes. Additionally, many LDS patients
      do not meet the inclusion criteria of SPORT, and extrapolating the results to these patients
      is inappropriate. The currently available evidence provides surgeons with some general
      principles to help guide decision-making but does not inform decision-making at the
      individual patient level.

      Many studies have evaluated the effect of specific patient and disease characteristics on
      surgical outcomes for spinal stenosis. These have generally shown worse surgical outcomes for
      patients with medical and psychological comorbidities, lower socioeconomic status and
      educational attainment, smokers, those with predominant back pain, those receiving workers'
      compensation, and patients involved in litigation. However, subgroup analysis of the SPORT
      degenerative spondylolisthesis cohort, the first study that evaluated predictors of both
      surgical and non-operative LDS outcomes, demonstrated that these factors tended to predict
      both worse surgical and non-operative outcomes. As a result, most of these subgroups tended
      to have a similar treatment effect of surgery (i.e. relative advantage of surgical compared
      to non-operative outcomes) even if their absolute degree of improvement with surgery was
      less. While these data suggest that most LDS patients meeting the SPORT inclusion criteria
      will improve more with surgery than with non-operative treatment, many LDS patients do not
      meet the SPORT inclusion criteria, and evidence is needed to provide treatment guidelines for
      these patients.

      In an ideal world, randomized-controlled trials (RCT) would be performed for multiple
      subgroups in order to compare outcomes among all available treatment options. The SPORT LDS
      RCT demonstrated the difficulty in performing a seemingly straightforward RCT comparing
      surgery to non-operative treatment, with only 64% of patients assigned to surgery having
      undergone an operation within 2 years, and 49% of patients randomized to non-operative
      treatment having undergone surgery by 2 years. Given that it is not possible to perform
      sufficiently powered RCTs to compare surgical and non-operative outcomes for multiple LDS
      subgroups, other methods must be considered to generate guidelines to help surgeons and LDS
      patients select the most appropriate treatment based on their individual characteristics. One
      such alternative is the RAND appropriateness method (RAM), which combines a detailed review
      of the literature with a modified Delphi panel approach to create appropriateness criteria
      based on collective expert opinion. A major strength of the RAM is that is involves a high
      level of clinical detail, allowing for treatment recommendations to be made based on a number
      of relevant patient and disease characteristics that can be applied to individual patients.
      The RAM has been widely used and studied by several groups in various countries in relation
      to different spinal problems. The RAM is considered most useful for procedures that are used
      frequently, associated with a substantial amount of morbidity and/or mortality, consume
      significant resources, have wide variation among geographic areas in rates of use, and whose
      use is controversial. All these criteria apply to the procedures commonly used in the
      surgical treatment of LDS. Depending on the definition of success, success rates at 1 year
      after surgery range from 50% to 94%. The rate of lumbar fusion in the United States Medicare
      population has been shown to vary nearly 20-fold across hospital referral regions. In the
      SPORT LDS cohort, significant differences were found across different study centers in
      patients' baseline neurological deficit, stenosis location and severity, and number of
      stenotic levels as well as in their functional outcome out to 4 years after surgery. High
      levels of geographic variation are frequently attributed to uncertainty about the most
      appropriate treatment for a given condition, usually reflecting a lack of strong evidence.
      Given the lack of treatment recommendations that can be applied at the individual LDS patient
      level, an international group of experts were convened to use the RAM to create
      appropriateness criteria for surgery for LDS.3

      The RAM process included 14 experts from the USA, UK, Belgium, Sweden, Norway, Spain,
      Switzerland, and Hungary with backgrounds in orthopaedic surgery, neurosurgery, rheumatology,
      and physical medicine. The experts considered the appropriateness of decompression alone,
      uninstrumented fusion with or without decompression, and instrumented fusion with or without
      decompression for 744 patient scenarios. The variables defining the scenarios included
      symptomatology (back pain, radicular pain, and/or neurogenic claudication), severity of
      neurological deficit, presence of significant foraminal and/or central stenosis, level of
      disability, presence of significant medical comorbidities, clinically relevant "instability",
      and the presence of significant psychosocial "yellow flags". The appropriateness of each type
      of surgery was rated on a 1-9 scale (1-3 inappropriate, 4-6 uncertain, and 7-9 appropriate)
      in two separate rounds by the expert panel. Surgery of one type or another was considered
      appropriate in 27% of scenarios, uncertain in 41%, and inappropriate in 31%. In general,
      scenarios in which symptoms were limited to back pain in the absence of instability were
      considered inappropriate for surgery, whereas the presence of radiculopathy or claudication,
      neurologic deficit, and instability increased the likelihood of a scenario being considered
      appropriate for surgery. The presence of medical comorbidities and "yellow flags" decreased
      the likelihood of a scenario being considered appropriate for surgery. There was widespread
      disagreement about the appropriate use of instrumentation, but, in general, fusion of some
      variety was more likely to be considered appropriate in the presence of back pain or
      instability.

      The RAM was successfully employed to develop appropriateness criteria for LDS surgery. Prior
      to widespread clinical implementation, the results need to be validated in the LDS
      population. If validated successfully, a computer-based algorithm could be developed to help
      surgeons and patients select treatment using the appropriateness criteria. This would
      represent a significant advancement in shared decision making for LDS, effectively moving
      from population-based recommendations to those that can be applied at the individual patient
      level.
observational model: Cohort
time perspective: Prospective
measure: Core Outcome Measures Index
time frame: 12-months Post-Treatment
measure: Oswestry Disability Index
time frame: 12-months Post-Treatment
measure: Global Outcome of Treatment Questions
time frame: 12-months Post-Treatment
description: Questions with 5 response categories, dichotomized to "good" and "poor"
measure: Satisfaction with Care
time frame: 12-months Post-Treatment
description: Questions with 5 response categories, dichotomized to "good" and "poor"
measure: Complications from Treatment
time frame: 12-months Post-Treatment
description: Questions with 5 response categories, dichotomized to "good" and "poor"
measure: Further Treatment after Initial Treatment
time frame: 12-months Post-Treatment
description: Questions with 5 response categories, dichotomized to "good" and "poor"
arm group label: LDS Patients
description: All patients with a diagnosis of single-level Lumbar Degenerative Spondylolisthesis who present to the DHMC Spine Center.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adam M Pearson, MD
role: Principal Investigator
affiliation: Dartmouth-Hitchcock Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: Adam M. Pearson
investigator title: Staff Physician
mesh term: Spondylolisthesis
sharing ipd: Yes