Assessment of Studies Evaluating Spinal Manipulative Therapy and Infectious Disease and Immune System Outcomes

Key Points Question Is spinal manipulative therapy associated with changes in the immune system? Findings In this systematic review of 13 studies comprising 795 participants, no clinical studies investigated the efficacy or effectiveness of spinal manipulative therapy in preventing or improving disease-specific outcomes among patients with infectious disease. Preliminary laboratory experiments indicated that spinal manipulative therapy may, in the short term, be associated with levels of change in immunological biomarkers among asymptomatic participants. Meaning These findings suggest that, given the limitations of the evidence, claims that spinal manipulative therapy is associated with changes in the immune system are premature and further clinical studies should be completed.


Data Items
Information extracted from each study included study characteristics, (e.g. author, year and country of publication, study design, sample size, length of follow up), participant characteristics (e.g., age, and body region treated), intervention characteristics (e.g., description of interventions and comparison groups), and outcome data (e.g., incidence of infection or infectious disease, disease-specific outcomes, changes in the levels of immunological, endocrine and other physiological biomarkers).

Classification of Clinical Trial Phases
We categorized RCTs into the different phases of clinical trials as described by Campbell et al. 21 The purpose of a phase 0 (exploratory) study is to gather preliminary data on whether the intervention behaves as expected in humans based on preclinical studies, and involves limited human exposure (10-15 healthy volunteers) to the intervention, with no therapeutic or diagnostic goals. 21 A phase 1 (safety) study aims to determine safety of the intervention and typically involves 20-80 healthy volunteers. 21 A phase 2 (biologic activity) study aims to establish proof of concept that the intervention has biologic activity, usually involving 100-300 patients with specific diseases. 21 A phase 3 (efficacy) study aims to confirm the efficacy and effectiveness of the intervention, monitor side effects, and frequently involves 300-3000 patients with specific diseases. 21 A phase 4 (post-marketing/confirmatory) study aims to provide surveillance and additional information on the intervention's risks, benefits and best use after the intervention is approved for human use, and involves several thousand patients treated with the intervention. 21

Statistical Analysis
We reported or computed (when data were available), the incidence and 95% confidence intervals (CI) of infection or infectious disease, and mean difference and 95% CI in change in the level of biomarkers. We reported or calculated the pre-post difference in means or mean differences between groups based on data derived from regression models. Incidence was measured by calculating the number of new cases of infection or infectious disease in a group divided by the total number of participants in the same group. Confidence intervals were calculated using incidence of infection or infectious disease in each group, total number of participants in each group, and α = 0.05.

Evidence Synthesis
We synthesized the evidence from high and acceptable quality studies according to the Synthesis without Meta-Analysis (SWiM) Guideline, 22 study objective, and type of biomarker. We restricted our synthesis to studies with high or acceptable quality because low/unacceptable quality studies are more likely to yield biased estimates of effect sizes. 23

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(manipulat* adj3 (spinal or spine or low* back or joint* or lumbar or neck or therap* or thoracic or cervical or intervention* or MSK or manage* or musculoskeletal or treat* or vertebr*)).ab,ti.

16
(mobili?at* adj3 (spinal or spine or low* back or joint* or lumbar or neck or thoracic or cervical or MSK or musculoskeletal or vertebr* or therap* or treat* or intervention* or manage*)).ab,ti.