Friedman, Deborah I

Objective To better understand the utility of using pain freedom and most bothersome headache‐associated symptom (MBS) freedom as co‐primary endpoints in clinical trials of acute migraine interventions. Background Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co‐primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain‐free and MBS‐free at 2 hours post‐dose, was significantly higher than for placebo. Methods We undertook a post‐hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co‐primary endpoints of pain relief, nausea, photophobia, and phonophobia. Results Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n = 79), phonophobia (n = 43), and nausea (n = 37). Two‐hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo ( P = .02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% ( P = .05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively ( P = .01). Two‐hour freedom from the MBS for active drug vs placebo were 67% vs 35% ( P < .01) for photophobia, 55% vs 43% ( P = .45) for phonophobia, and 89% vs 58% for nausea ( P = .04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea. Conclusion In this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co‐primary endpoints.

Objective To survey neurology residency program directors (PDs) on trainee exposure, supervision, and credentialing in procedures widely utilized in headache medicine. Background Clinic‐based procedures have assumed a prominent role in headache therapy. Headache fellows obtain procedural competence, but reliance on fellowship‐trained neurologists cannot match the population eligible for treatments. The inclusion of educational modules and mechanisms for credentialing trainees pursuing procedural competence in residency curricula at individual programs is not known. Methods A web‐based survey of US neurology residency PDs was designed by the American Headache Society (AHS) procedural special interest section in collaboration with AHS and American Academy of Neurology's Headache and Facial Pain section leadership. The survey addressed exposure, training, and credentialing in: (1) onabotulinumtoxinA (onabotA) injections, (2) extracranial peripheral nerve blocks (PNBs), and (3) trigger point injections (TPIs). Results Fifty‐five PDs (42.6%) completed the survey. Compared to noncompleters, survey completers were more likely to feature headache fellowships at their institutions (38.2% vs 10.8%, P =0.0002). High exposure (onabotA=90.9%, PNBs=80.0%, TPIs=70.9%) usually featured hands‐on patient instruction (66.2%) and lectures (55.7%). Supervised performance rates were high (onabotA=65.5%, PNBs=60.0%, TPIs=52.7%), usually in continuity clinic (60.0%) or headache elective (50.9%). Headache specialists (69.1%) or general neurology (32.7%) faculty most commonly trained residents. Formal credentialing was uncommon (16.4‐18.2%), mostly by documenting supervised procedures (25.5%). Only 27.3% of programs permitted trainees to perform procedures independently. Most PDs felt procedural exposure (80.0‐90.9%) and competence (50.9‐56.4%) by all trainees was important. Conclusions Resident exposure to procedures for headache is high, but credentialing mechanisms, while desired by most PDs, are not generally in place. Implementation of a credentialing process may ensure trainees enter practice with the ability to perform procedures safely and effectively.

Objective To describe a standardized methodology for the performance of peripheral nerve blocks ( PNB s) in the treatment of headache disorders. Background PNBs have long been employed in the management of headache disorders, but a wide variety of techniques are utilized in literature reports and clinical practice. Methods The A merican H eadache S ociety S pecial I nterest S ection for PNBs and other I nterventional P rocedures convened meetings during 2010‐2011 featuring formal discussions and agreements about the procedural details for occipital and trigeminal PNBs . A subcommittee then generated a narrative review detailing the methodology. Results PNB indications may include select primary headache disorders, secondary headache disorders, and cranial neuralgias. Special procedural considerations may be necessary in certain patient populations, including pregnancy, the elderly, anesthetic allergy, prior vasovagal attacks, an open skull defect, antiplatelet/anticoagulant use, and cosmetic concerns. PNBs described include greater occipital, lesser occipital, supratrochlear, supraorbital, and auriculotemporal injections. Technical success of the PNB should result in cutaneous anesthesia. Targeted clinical outcomes depend on the indication, and include relief of an acute headache attack, terminating a headache cycle, and transitioning out of a medication‐overuse pattern. Reinjection frequency is variable, depending on the indications and agents used, and the addition of corticosteroids may be most appropriate when treating cluster headache. Conclusions These recommendations from the A merican H eadache S ociety S pecial I nterest S ection for PNBs and other I nterventional P rocedures members for PNB methodology in headache disorder treatment are derived from the available literature and expert consensus. With the exception of cluster headache, there is a paucity of evidence, and further research may result in the revision of these recommendations to improve the outcome and safety of these interventions.