Table 2.

Selected supporting studies.

Measure/Author	Sample Size	Methodology	Prediction Type	Results
HADS Jamison et al., 2012	N=268 opioid-using patients with chronic LBP	12-week RCT: ER Hydromorphone vs. Placebo	Some elements of effect modification analyses	Patients with high baseline HADS scores were more likely to drop out; those with moderate-high HADS scores had higher pain and disability ratings (i.e., less analgesic benefit) during hydromorphone treatment.
Wasan et al., 2009	N=86 patients with chronic axial pain undergoing Medial Branch Blocks	Prospective cohort study with 1-month follow-up.	General prediction	Patients with high baseline HADS scores were less likely to obtain significant pain relief (10% vs. 45% in the low HADS group) at 1 month follow-up.
PCS Rakel et al., 2014	N=317 patients undergoing total knee replacement randomized to TENS, placebo TENS, or standard care	RCT with 6-week follow-up	Effect modification	In the TENS groups, patients with higher PCS scores had more pain and less range of motion at 6 weeks. No associations between PCS and pain outcomes were observed in the other groups.
PROMIS Karp et al., 2014	N= 159 LBP patients treated with epidural steroid injections	Observational cohort study with 1-month and 3-month follow-up.	General prediction	A number of PROMIS subscales were assessed, including those for negative affect, sleep, pain behavior and pain interference (these were used as outcomes). Negative affect and sleep prospectively predicted more pain and dysfunction at 3 months.
SF-MPQ 2 Carroll et al.,, 2010	N=71 patients with “suspected neuropathic pain”	Within-subjects trial of pain relief with saline infusion compared to IV lidocaine infusion.	Effect modification	Patients describing their pain as “heavy” at baseline experience greater pain relief from IV lidocaine but do not differ in placebo pain relief.
PQAS Gammaitoni et al., 2013	N=99 patients with peripheral neuropathic pain, treated with pregabalin in an enriched enrollment randomized withdrawal design (EERW).	EERW trial with 3-week treatment period following titration.	Effect modification	Higher scores on the PQAS “Paroxysmal Pain” and “Deep Pain” scales were associated with better response to pregabalin, but were unassociated with placebo responses.
painDETECT Hober et al., 2014	N=822 patients with neuropathic pain	12 weeks of treatment with 8% capsaicin patches (high-concentration topical capsaicin).	General prediction	High baseline scores (>18) predicted more pain reduction (~24% pain reduction) relative to low (<13) scores (~13% pain reduction).
NPSI Bouhassira et al., 2014	N=804 patients with painful diabetic neuropathy	RCT of duloxetine (60mg) vs. pregabalin (300mg) monotherapy, with non-responders randomized to either high-dose monotherapy or combination therapy	Effect modification	The cluster of patients with the lowest NPSI scores had the largest separation favoring duloxetine over pregabalin when comparing monotherapies.
Sleep Vinik et al., 2014	N= 4,527 patients with DPN or PHN, pooled from 16 RCTs	Data was pooled from 16 randomized, placebo-controlled trials of pregabalin in patients with PHN or DPN. Sleep disturbance was measured using a 0–10 self-report item on Daily Sleep Interference.	Effect modification	Across studies, PHN and DPN patients with severe sleep disruption at baseline derived substantially more pain reduction from pregabalin than placebo (p’s< .001).
QST Demant et al., 2014	N=97 patients with peripheral neuropathic pain	Crossover RCT of 6 weeks oxcarbazepine (up to 2,400mg; mean daily dose ~1,800 mg) vs. 6 weeks placebo. Patients phenotyped at baseline using a bedside version of the DFNS protocol.	Effect modification	Patients with “irritable nociceptors” (i.e., sensory gain on at least some measures of thermal and mechanical QST) had a better response to oxcarbazepine. No group differences in placebo responses.
Simpson et al., 2010	N= 302 patients with painful HIV-associated neuropathy.	RCT of pregabalin (mean dose 386 mg) vs. placebo with 2 weeks dose adjustment, 12 weeks maintenance, and an optional 3-month open-label extension.	Effect modification	Patients with the most mechanosensitivity to pinprick at baseline had good pain reduction with pregabalin (p= .01) while low-to-moderate sensitivity subjects had no pain reduction (p= .87). No effects on placebo analgesia.
CPM Yarnitsky et al., 2012	N= 30 patients with DPN	Treatment with 1 week of placebo followed by 1 week of duloxetine 30mg, then 4 weeks of duloxetine 60mg.	Some elements of effect modification analyses	Patients with worse CPM at baseline got the most reduction in pain with duloxetine treatment. A greater increase in CPM correlated with more pain reduction as well.
Niesters et al., 2014	N= 24 patients with DPN	Randomization to 4 weeks of tapentadol SR (mean daily dose = 433mg) vs. placebo. CPM Methods: test stimulus= heat pain, conditioning stimulus = cold pressor.	Effect modification	On average, patients did not show CPM at baseline. Those randomized to tapentadol SR developed CPM, those randomized to placebo did not. Larger magnitude of CPM increase correlated with greater pain reduction.

CPM= Conditioned Pain Modulation; DFNS= German Research Network on Neuropathic Pain (translated); DPN= Diabetic Painful Neuropathy; EERW= Enriched Enrollment Randomized Withdrawal; ER= Extended Release; HADS= Hospital Anxiety and Depression Scale; HIV= Human Immunodeficiency Virus; ISI= Insomnia Severity Index; IV= Intravenous; LBP= Low Back Pain; NPSI= Neuropathic Pain Symptom Inventory; PCS= Pain Catastrophizing Scale; PHN= Post-Herpetic Neuralgia; PILL= Pennebaker Inventory of Limbic Languidness; PROMIS= Patient Reported Outcomes Measurement Information System; PQAS= Pain Quality Assessment Scale; PSQI= Pittsburgh Sleep Quality Index; QST= Quantitative Sensory Testing; RCT= Randomized Controlled Trial; SF-MPQ= Short Form McGill Pain Questionnaire; StEP= Standardized Evaluation of Pain; TENS= Transcutaneous Electrical Nerve Stimulation