Organization of the study
This study occurred at the Madigan Army Medical Center (MAMC) in Fort Lewis, Washington. The Osteopathic Research Center at the University of North Texas Health Science Center was the clinical research organization (CRO) for this RCT. The CRO team consisted of two blinded osteopathic physicians, one un-blinded social scientist, and an un-blinded study biostatistician. The CRO worked closely with the MAMC study team led by the site principal investigator (site PI), an active duty osteopathic family physician, who served as the blinded study evaluating physician (SEP). The SEP screened and examined all subjects in a blinded fashion for medical exclusion criteria prior to enrollment and before each study visit, managed all medications related to back pain, and retained these data in separate confidential records on each study subject.
The non-blinded study treatment physicians (STPs) included three osteopathic and one allopathic physicians with previous training in manual medicine who were commissioned officers in the medical corps. The site clinical research coordinator (CRC) reported to the site PI. The CRO designed the protocol and the data collection forms, trained the site STPs and CRC, and managed the data entry and analysis. Sealed randomization envelopes were prepared by the CRO and mailed to the study CRC for insertion into blank study charts for opening by the STP at the first study visit. Assessment charts were kept physically separate from the study treatment charts that were accessible only to the STPs, thereby maintaining blinding of the SEP and the CRC. A Data and Safety Monitoring Board (DSMB) was created to monitor patient safety, establish retention, dropping and stopping criteria, and ensure data collection integrity.
DoD LBP guidelines
The DoD usual care protocol for military personnel with ALBP at the time of the study consisted of the following.
- Advice: assuring the soldier that most episodes of ALBP will resolve uneventfully within 6 weeks; encouraging the soldier to maintain as close to normal activity as is tolerable and to avoid bed rest of longer than 24 hours; and advising the use of non-steroidal anti-inflammatory drugs unless contraindicated.
- Prescribing muscle relaxants for up to one week or low dose opiates (codeine; propoxyphene) unless contraindicated.
- Passive modalities such as ice or heat for symptomatic relief. If the soldier’s pain was not improved in two weeks, guidelines required that the soldier be re-evaluated for ‘red flags,’ a different non-steroidal anti-inflammatory drug considered, and be given a referral to physical therapy while continuing to be followed in the primary care clinic.
provides details on subjects’ recruitment, enrollment, and retention, and the final number of subjects in the analyses. A power analysis performed prior to the study had indicated that 36 subjects would be needed in each group to detect a medium (0·36) effect size with alpha at 0·05 and 85% power. A total of 63 patients were randomized to a treatment group.
Soldiers presenting with a new complaint of ALBP, defined as a minimum of 30 days hiatus of pain from previous LBP episodes, were recruited daily at the MAMC clinics. The CRC verified that a soldier met the first level screening criteria. To pass the first screening level, a soldier had to be male or female, of any racial or ethnic origin, and between 18 and 35 years old. If a woman’s onset of her last menstrual cycle was >28 days prior to enrollment, she was given a urine pregnancy test, and excluded from the study if pregnant.
The second level screening was performed by the blinded SEP. A soldier could not enroll in the study if the SEP found evidence of a serious neurological, rheumatologic, or orthopedic condition present on examination, including spondylolysis, spondylolisthesis, fracture, nerve impingement, tumors, or infections. Also, soldiers were not eligible if there was clinical evidence of a leg length discrepancy greater than 13 mm or if their leg pain was worse than their back pain indicating possible radiculopathy. Soldiers could not have had manual therapy for this episode of ALBP. Last, they could not enroll in the study if there was any known inability to give informed consent or the soldier knew at that time that he or she would be unable to stay in the study for the four week protocol and participate in the end-point outcomes measures for the trial.
After enrollment, a subject would be dropped from the study if the SEP determined the need for additional clinical tests such as radiographs or orthopedic consultation, or found a red-flag condition. Red-flag conditions were those the SEP believed required immediate medical diagnostics and/or evaluation for treatment including physical signs or symptoms of abnormal reflexes, neurogenic bowel or bladder, erectile dysfunction, lower extremity weakness or paralysis, or dermatomal sensory loss suggestive of a spinal cord or nerve root injury. One subject was dropped from the study for red-flag symptoms during that person’s second week of enrollment. The DSMB found no other significant patient safety concerns during the study.
displays the OMT protocol used in this study. The OMT protocol used in this study has been previously published as it was also used in another research study.28
Treatments occurred once per week for four weeks, not closer than 7 or more than 10 days apart. Treatments were administered by the non-blinded STPs trained in the protocol. Subjects were instructed to refrain from receiving other manual therapies during the four weeks of the trial. The STPs completed four hands-on training sessions in the study OMT protocol taught by two CRO osteopathic physicians, board certified in neuromusculoskeletal medicine and osteopathic manipulative medicine. Two training sessions occurred prior to the start of, and two occurred during the trial. A DVD refresher video was also provided to ensure maintenance of protocol skills and minimize variation among STPs in the application of the treatments.
Osteopathic manipulative treatment protocol.
Study outcome measures
The primary outcome of interest in this RCT was pain, with a secondary outcome being back related functioning. The QVAS for aspects of pain intensity was administered using a 10 point scale for each of these aspects: ‘Pain Now’, ‘Pain Typical’, ‘Pain at Worst’, and ‘Pain at Best’. The scale ranged from 1 to 10 with 1 corresponding to ‘No pain’, and 10 corresponding to ‘Worst possible pain’. The RMDQ measured back-specific functioning, with 24 statements that subjects endorse if it describes them at the time of the assessment. We also took a measure of quality of life using the Short Form Health Survey (SF-36) at baseline only to determine if the two treatment groups differed in their self-perceived overall health status. Other measures included a Patient Expectation Questionnaire (PEQ), developed specifically for this trial, one question about perceived overall improvement during the trial on a scale of 1 to 7, and one question regarding satisfaction with treatment received using a scale of 1 to 10.
Medication usage can be addressed using a variety of methods. Medication logs are sometimes used in this type of study. However, asking soldiers to maintain a medication log became impractical and unreliable. Therefore, for this study the blinded SEP’s prescribing practices were obtained from the records. Prescribing practices for both Schedule 1 medications (naproxen, ibuprofen, and acetaminophen) and Schedule 2 medications (cyclobenzaprine and acetaminophen with codeine) were identified in the data collection form.
All subjects followed the same study procedures. There were five study visits, visit 1 through visit 4 for the treatment protocol, and visit 5 for a follow-up end-point interview. Outcome measures for treatment effects were collected one week after the first, second, and third treatment sessions, and four weeks after the last treatment session. Participants received and signed informed consent documents prior to enrollment.
After enrolling in the study, and before randomization and treatment, each subject completed the SF-36, the QVAS, the RMDQ, the PEQ and the one question regarding satisfaction with treatment. Immediately following the completion of baseline measures, the subject proceeded to see the Study Treating Physician (STP) for randomization and the first treatment session. The STP was located in an area of the clinic physically separated from the CRC and SEP offices to protect blinding.
At visit 1, the STP opened the randomization envelope and assigned the study subject to either the OMT group or the usual care only (UCO) group. Subjects assigned to the UCO group left the STP office with instructions to follow the DoD guidelines. Subjects randomized to the treatment group received the first OMT treatment and the DoD guideline instructions.
At visits 2, 3, and 4, the subjects met first with the blinded SEP for red-flag screening and medication evaluation, next with the blinded CRC to complete the QVAS and the RMDQ, and finally with the STP who followed the protocol for each group. Thus, study subjects completed assessments of pain and functioning one-week after each of the first three manipulative medicine treatments. The physical separation between the SEP and CRC offices and the STP treatment room was sufficiently extensive to maintain blinding.
Visit 5 occurred four weeks after the last treatment session at visit 4, at which time the CRC collected a last round of outcome measures, and asked the single question regarding satisfaction with treatment.
The list below specifies the sequence of study visits.
V1 (Randomization): Outcomes at Baseline, followed by Treatment Session 1
V2 (One week Post-Treatment 1): Outcomes Post-treatment 1 followed by Treatment Session 2
V3 (One week Post-Treatment 2): Outcomes Post-treatment 2 followed by Treatment Session 3
V4 (One week Post-Treatment 3): Outcomes Post-treatment 3 followed by Treatment Session 4
V5 (Four weeks Post-Treatment 4): End-point Interview Outcomes Post-Treatment Session 4
Thus, five rounds of outcome measurements for pain and functioning were collected by the CRC.
Data management and statistical methods
Data were recorded in study booklets by the blinded CRC. Study booklets were copied and de-identified, using only a study ID number linked to a list maintained by the CRC, and mailed to the CRO where the data were entered in a blinded fashion. Only the study biostatistician and the DSMB members were informed of the subjects’ respective study groups. As required by the DSMB, the study biostatistician at the CRO performed a preliminary data analysis mid-point during the study for the DSMB, producing open and closed reports. Closed reports were provided to the CRO, the site PI and the CRC. Final analysis was completed in May 2007, and the DSMB released the final reports in June 2008 to the CRO and the sponsor.
The DSMB determined that only those subjects with two completed treatment visits would be considered as viable study participants for the analysis. Study subjects with only one visit would have had only pre-treatment baseline data, and no post-treatment data. Therefore, any subjects with only one study visit were not included in the study, and thus not included in any analysis. Data were analyzed using the statistical software package SPSS (version 17·0; SPSS Inc., Chicago, IL, USA). We utilized both intention to treat (ITT) and per-protocol analyses to explore whether the results were different when including only those subjects who completed all outcome measures.
Outcome variables of pain and functioning were treated as continuous variables for analysis, based on the distribution of the underlying construct as well as inspection of baseline distributions for the sample. Chi-square and t-test analyses were used to compare the two treatment groups at baseline.
A repeated measures t-test was used to examine changes between baseline and trial endpoint. We utilized a repeated measures Analysis of Variance to test both the primary hypothesis that the OMT group would report greater improvement in pain and functioning than the UCO group, and to examine the question of whether OMT improved pain and functioning sooner than UCO.
In addition, we were interested in when a clinically meaningful improvement of at least 30% from baseline occurred in pain and functioning. Thus we utilized a Cox Regression Analysis to examine the time to clinically meaningful improvement for the OMT group compared to the UCO group.
Last, we calculated correlation coefficients to examine the possible relationships between treatment expectations and pain and functioning, and performed t-tests to compare the two groups on patient expectations, overall satisfaction and self-reported improvement scores.