Core outcome measurement instruments for clinical trials in nonspecific low back pain.

To standardize outcome reporting in clinical trials of patients with nonspecific low back pain, an international multidisciplinary panel recommended physical functioning, pain intensity, and health-related quality of life (HRQoL) as core outcome domains. Given the lack of a consensus on measurement instruments for these 3 domains in patients with low back pain, this study aimed to generate such consensus. The measurement properties of 17 patient-reported outcome measures for physical functioning, 3 for pain intensity, and 5 for HRQoL were appraised in 3 systematic reviews following the COSMIN methodology. Researchers, clinicians, and patients (n = 207) were invited in a 2-round Delphi survey to generate consensus (≥67% agreement among participants) on which instruments to endorse. Response rates were 44% and 41%, respectively. In round 1, consensus was achieved on the Oswestry Disability Index version 2.1a for physical functioning (78% agreement) and the Numeric Rating Scale (NRS) for pain intensity (75% agreement). No consensus was achieved on any HRQoL instrument, although the Short Form 12 (SF12) approached the consensus threshold (64% agreement). In round 2, a consensus was reached on an NRS version with a 1-week recall period (96% agreement). Various participants requested 1 free-to-use instrument per domain. Considering all issues together, recommendations on core instruments were formulated: Oswestry Disability Index version 2.1a or 24-item Roland-Morris Disability Questionnaire for physical functioning, NRS for pain intensity, and SF12 or 10-item PROMIS Global Health form for HRQoL. Further studies need to fill the evidence gaps on the measurement properties of these and other instruments.

Porous silicon nitride spacers versus PEEK cages for anterior cervical discectomy and fusion: clinical and radiological results of a single-blinded randomized controlled trial.

PURPOSE: Anterior cervical discectomy with fusion is a common procedure for treating radicular arm pain. Polyetheretherketone (PEEK) plastic is a frequently used material in cages for interbody fusion. Silicon nitride is a new alternative with desirable bone compatibility and imaging characteristics. The aim of the present study is to compare silicon nitride implants with PEEK cages filled with autograft harvested from osteophytes. METHODS: The study is a prospective, randomized, blinded study of 100 patients with 2 years follow-up. The primary outcome measure was improvement in the Neck Disability Index. Other outcome measures included SF-36, VAS arm pain, VAS neck pain, assessment of recovery, operative characteristics, complications, fusion and subsidence based on dynamic X-ray and CT scan. RESULTS: There was no significant difference in NDI scores between the groups at 24 months follow-up. At 3 and 12 months the NDI scores were in favor of PEEK although the differences were not clinically relevant. On most follow-up moments there was no difference in VAS neck and VAS arm between both groups, and there was no statistically significant difference in patients' perceived recovery during follow-up. Fusion rate and subsidence were similar for the two study arms and about 90% of the implants were fused at 24 months. CONCLUSIONS: Patients treated with silicon nitride and PEEK reported similar recovery rates during follow-up. There was no significant difference in clinical outcome at 24 months. Fusion rates improved over time and are comparable between both groups.

Core outcome domains for clinical trials in non-specific low back pain.

PURPOSE: Inconsistent reporting of outcomes in clinical trials of patients with non-specific low back pain (NSLBP) hinders comparison of findings and the reliability of systematic reviews. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials. In 1998, Deyo et al. recommended a standardized set of outcomes for LBP clinical research. The aim of this study was to update these recommendations by determining which outcome domains should be included in a COS for clinical trials in NSLBP. METHODS: An International Steering Committee established the methodology to develop this COS. The OMERACT Filter 2.0 framework was used to draw a list of potential core domains that were presented in a Delphi study. Researchers, care providers and patients were invited to participate in three Delphi rounds and were asked to judge which domains were core. A priori criteria for consensus were established before each round and were analysed together with arguments provided by panellists on importance, overlap, aggregation and/or addition of potential core domains. The Steering Committee discussed the final results and made final decisions. RESULTS: A set of 280 experts was invited to participate in the Delphi; response rates in the three rounds were 52, 50 and 45%. Of 41 potential core domains presented in the first round, 13 had sufficient support to be presented for rating in the third round. Overall consensus was reached for the inclusion of three domains in this COS: 'physical functioning', 'pain intensity' and 'health-related quality of life'. Consensus on 'physical functioning' and 'pain intensity' was consistent across all stakeholders, 'health-related quality of life' was not supported by the patients, and all the other domains were not supported by two or more groups of stakeholders. Weighting all possible argumentations, the Steering Committee decided to include in the COS the three domains that reached overall consensus and the domain 'number of deaths'. CONCLUSIONS: The following outcome domains were included in this updated COS: 'physical functioning', 'pain intensity', 'health-related quality of life' and 'number of deaths'. The next step for the development of this COS will be to determine which measurement instruments best measure these domains.

A core outcome set for clinical trials on non-specific low back pain: study protocol for the development of a core domain set.

BACKGROUND: Low back pain (LBP) is one of the most disabling and costly disorders affecting modern society, and approximately 90% of patients are labelled as having non-specific LBP (NSLBP). Several interventions for patients with NSLBP have been assessed in clinical trials, but heterogeneous reporting of outcomes in these trials has hindered comparison of results and performance of meta-analyses. Moreover, there is a risk of selective outcome reporting bias. To address these issues, the development of a core outcome set (COS) that should be measured in all clinical trials for a specific health condition has been recommended. A standardized set of outcomes for LBP was proposed in 1998, however, with evolution in COS development methodology, new instruments, interventions, and understanding of measurement properties, it is appropriate to update that proposal. This protocol describes the methods used in the initial step in developing a COS for NSLBP, namely, establishing a core domain set that should be measured in all clinical trials. METHODS/DESIGN: An International Steering Committee including researchers, clinicians, and patient representatives from four continents was formed to guide the development of this COS. The approach of initiatives like Core Outcome Measures in Effectiveness Trials (COMET) and Outcome Measures in Rheumatology (OMERACT) was followed. Participants were invited to participate in a Delphi study aimed at generating a consensus-based core domain set for NSLBP. A list of potential core domains was drafted and presented to the Delphi participants who were asked to judge which domains were core. Participant suggestions about overlap, aggregation, or addition of potential core domains were addressed during the study. The patients' responses were isolated to assess whether there was substantial disagreement with the rest of the Delphi panel. A priori thresholds for consensus were established before each Delphi round. All participants' responses were analysed from a quantitative and qualitative perspective to ascertain that no substantial discrepancies between the two approaches emerged. DISCUSSION: We present the initial step in developing a COS for NSLBP. The next step will be to determine which measurement instruments adequately cover the domains.

The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol.

BACKGROUND: Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion.Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. METHODS/DESIGN: This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18-75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. DISCUSSION: In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled trial in which the silicon nitride cage is compared with the PEEK cage in patients with symptomatic degenerative lumbar disc disorders. TRIAL REGISTRATION: NCT01557829.

The CASCADE trial: effectiveness of ceramic versus PEEK cages for anterior cervical discectomy with interbody fusion; protocol of a blinded randomized controlled trial.

BACKGROUND: Anterior cervical discectomy with interbody fusion cages is considered the standard surgical procedure in patients with cervical disc herniation. However, PEEK or metal cages have some undesirable imaging characteristics, leading to a search for alternative materials not creating artifacts on images; silicon nitride ceramic. Whether patients treated with silicon nitride ceramic cages have similar functional outcome as patients treated with PEEK cages is not known. We present the design of the CASCADE trial on effectiveness of ceramic cages versus PEEK cages in patients with cervical disc herniation and/or osteophytes. METHODS/DESIGN: Patients (age 18-75 years) with monoradicular symptoms in one or both arms lasting more than 8 weeks, due to disc herniation and/or osteophytes, are eligible for the trial. The study is designed as a randomized controlled equivalence trial in which patients are blinded to the type of cage for 1 year. The total follow-up period is 2 years. The primary outcome measure is improvement in the Neck and Disability Index (NDI). Secondary outcomes measures include improvement in arm pain and neck pain (VAS), SF-36 and patients' perceived recovery. The final elements of comparison are perioperative statistics including operating time, blood loss, length of hospital stay, and adverse events. Lateral plane films at each follow-up visit and CT scan (at 6 months) will be used to judge fusion and the incidence of subsidence. Based on a power of 90% and assuming 8% loss to follow-up, 100 patients will be randomized into the 2 groups. The first analysis will be conducted when all patients have 1 year of follow-up, and the groups will be followed for 1 additional year to judge stability of outcomes. DISCUSSION: While the new ceramic cage has received the CE Mark based on standard compliance and animal studies, a randomized comparative study with the golden standard product will provide more conclusive information for clinicians. Implementation of any new device should only be done after completion of randomized controlled effectiveness trials.