We thank the authors of the letters for their comments on our low back pain guideline (1) and evidence reviews (2, 3). Dr. Bjordal and colleagues note some methodological concerns with our review on medications for acute and chronic low back pain. To clarify, we performed a systematic review of a broad range of systematic reviews and included past systematic reviews when they were available and of sufficient quality. The idea that new systematic reviews of the primary literature should always be conducted when developing clinical practice guidelines is both unsupported by any empirical evidence and could be a poor use of scientific resources (4). Guideline panels need relevant, current, high-quality reviews of the evidence; if existing reviews fulfill those criteria, then it is wasteful to ignore them and conduct new ones. We included systematic reviews published in or after 2000 and identified higher-quality reviews by using a validated, quality-rating instrument (5, 6). Although systematic reviews should be updated, there is no compelling reason to ignore higher-quality Cochrane reviews (7) that satisfied our methodological criteria for inclusion but did not meet an updating deadline (8). Dr. Bjordal and colleagues suggest that we graded evidence for acetaminophen too positively. In their letter, they describe 1 trial as evaluating acute low back pain when it actually evaluated chronic low back pain (9). Otherwise, our descriptions of the evidence are similar (Appendix Tables 10 and 11 [2]). We agree that our evidence ratings for acetaminophen were generous given some inconsistency among trials of acute low back pain, small benefits, and a lack of direct evidence for chronic low back pain. In a subsequent Correction (10), we re-rated evidence for acetaminophen for acute low back pain as fair quality with moderate benefits and evidence for chronic low back pain as fair quality with small benefits. Because of acetaminophen's favorable safety profile compared with other pharmacologic therapies, these corrections do not change our recommendation to consider it as a first-line option (1).

For NSAIDs, skeletal muscle relaxants, and benzodiazepines, Dr. Bjordal and colleagues' focus on single outcomes from placebo-controlled trials reported in Cochrane reviews ignores much of the available evidence. Our assessments are based on both placebo- and active-controlled trials; non-Cochrane systematic reviews; data on various outcomes related to pain, function, and global efficacy; and indirect evidence from patients with other pain conditions (Appendix Tables 10 and 11 [2]). We also evaluated consistency between trials and across higher-quality systematic reviews (11). In addition, post hoc analyses, such as those presented by Dr. Bjordal and colleagues, can be misleading and should be interpreted with caution. For example, excluding trials on the basis of small differences in quality scores is problematic because of unpredictable associations between summary quality-rating scores and estimates of effects (12). We did not report data on mean improvement in pain scores from a Cochrane review of NSAIDs because of substantial, unexplained heterogeneity (P < 0.001) (7).

As Dr. Bjordal and colleagues surmised, we inverted relative risks (1/relative risk) for "no pain relief" with skeletal muscle relaxants and benzodiazepines (as reported in a Cochrane review [13]) to present results for a positive outcome (achieving pain relief) (2). However, this transformation was incorrect, because relative risks (unlike odds ratios) are not a symmetric statistic. We have corrected the article to show original results as reported in the Cochrane review (10). This correction will not change any conclusions, but we thank Dr. Bjordal and colleagues for noting the error.

We disagree with the assertion that there is enough evidence to establish the efficacy of LLLT and transcutaneous electrical nerve stimulation. In the case of LLLT, there is substantial diversity across trials in doses and types of laser, some inconsistency among higher-quality trials, and the possibility of publication bias. Our conclusion of insufficient evidence is similar to a recently published Cochrane review (14). For transcutaneous electrical nerve stimulation, the highest-quality, placebo-controlled trial found no benefit in chronic low back pain (15). In addition, it is inappropriate to pool studies of disparate patient populations and therapies (transcutaneous electrical nerve stimulation and neuromuscular stimulation) as proposed by Dr. Bjordal and colleagues, and 2 of the trials proposed for pooling found no benefits on pain or function with transcutaneous electrical nerve stimulation versus placebo (16, 17).

Dr. Bjordal and colleagues suggest that recommendations for therapy favor pharmacologic over nonpharmacologic options (1). In fact, we recommend either type of therapy (Figure 1, box 9 [1]), and strength of evidence and magnitude of benefits were graded similarly for several pharmacologic and nonpharmacologic therapies (Appendix Tables 5 and 6 [1]). However, recommendation 7 on nonpharmacologic therapies in general was graded "weak" because of relatively weak evidence for some suggested options (Appendix Tables 10 and 11 [3]), higher costs compared with first-line pharmacologic therapies, and less convenience (most nonpharmacologic options involve multiple provider visits). It would be appropriate to select a nonpharmacologic therapy over a pharmacologic one in patients who express such a preference, but the trade-offs should be discussed (20). Superficial heat is already recommended as a self-care option (Figure 2, Interventions box [1]).

We disagree with Dr. Ernst that our conclusions regarding rare risk for serious adverse events with spinal manipulation are misleading or downplay the risk for cerebrovascular events (3). Our review deals with low back pain and treatment with lumbar spinal manipulation. There are no reports of cerebrovascular events after lumbar spine manipulation or during treatment for low back pain (18, 19). Cervical manipulation is not a subject of our review or practice guideline.