Clinical Trial Funding Research Articles

The Genomic Landscape of Plasmablastic Lymphoma (PBL) - an L.L.M.P.P. Project

The Genomic Landscape of Plasmablastic Lymphoma (PBL) - an L.L.M.P.P. Project

A Large Multicenter Real-World Evidence (RWE) Analysis of Autoimmune (AI) Diseases and Lymphoma: Histologic Associations, Disease Characteristics, Survival, and Prognostication

A Large Multicenter Real-World Evidence (RWE) Analysis of Autoimmune (AI) Diseases and Lymphoma: Histologic Associations, Disease Characteristics, Survival, and Prognostication

Outcome of Relapsed and Refractory Peripheral T-Cell Lymphoma (PTCL) with Intention for Curative Therapy Incorporating High Dose Chemotherapy and Hematopoietic Stem Cell Transplant (HDC/SCT)

Outcome of Relapsed and Refractory Peripheral T-Cell Lymphoma (PTCL) with Intention for Curative Therapy Incorporating High Dose Chemotherapy and Hematopoietic Stem Cell Transplant (HDC/SCT)

Single-Cell Profiling Reveals Clinically Relevant Evolutionary Trajectories and Alternate Biologies in Human Follicular Lymphoma

Follicular lymphoma (FL) is an indolent lymphoma of mature B-cells but may transform to a more aggressive histology, most commonly diffuse large B cell lymphoma. Recurrent mutations associated with transformation have been identified; however, biological predictors to guide initial therapy have remained elusive. We hypothesized that clonal heterogeneity and patient-specific immune responses would contribute to variable clinical outcomes and that understanding the complexity of the entire tumor “ecosystem” would allow more individualized matching of patients with specific therapies.In prior ASH meetings, we presented preliminary analyses of B and T cell-focused phenotypic profiling of 155 newly diagnosed pre-treatment FL biopsy samples at single cell resolution by mass cytometry (CyTOF). These prior analyses unexpectedly revealed two distinct evolutionary trajectories which were independently reflected in both B and T cell compartments. One trajectory expectedly involved germinal center B cells (GCB); however, the other was more related to naïve/memory B-cells (NMB). Interestingly, cluster co-occurrence analysis suggested that the GCB and NMB trajectories were mutually exclusive of another and tended not to be found within the same tumor despite their high prevalences (χ 2 = 29.8, DF=1, p=4.8e-8; χ 2 test). Clustering analysis based on relative abundances of T cell subsets revealed 4 distinct immune patterns: Group 1 was characterized by naive T cells; Group 2 by T follicular helper (Tfh) cells; Group 3 by CD4+ regulatory T (Treg) and CD8 effector memory cells (CD8EM); and Group 4 by a diverse complement of naive, memory, and differentiated effector subsets.We report here further analyses, now incorporating DNA mutational and clinical outcome information. Tumors were parsed into 3 types based on the phenotype of the majority (>50%) of tumor cells present in the diagnostic biopsy: Type A tumors dominated by GCB cells (28% of samples), type B tumors dominated by NMB cells (18% of samples), and type nonA/nonB tumors dominated by neither GCB nor NMB cells (54% of samples).Type A tumors were significantly enriched for mutations in EZH2, TNFRSF14, and MEF2B, while no significant mutational associations were seen in type B and nonA/nonB tumors. Type B was significantly associated with increased risk of transformation, and when combined with a measure of intratumoral phenotypic diversity (“Entropy”), we found that type B tumors with high (above median) Entropy, representing 8.5% of all cases, exhibited a hazard ratio (HR) of 5.9 for transformation risk in comparison to all others combined (log-rank p<0.0001). Type B and high Entropy remained significant in multivariate analysis (p=0.043 and p=0.011, respectively), whereas high risk FLIPI score did not (p=0.962).We also investigated survival outcomes using a sub-cohort of 108 patients who had received bendamustine + rituximab (BR) as their primary therapy. Despite the association of type B tumors with transformation risk, patients with type nonA/nonB tumors exhibited the poorest outcomes as measured by disease-specific survival (DSS; 5yr survival 78% vs 98% for all others combined, log-rank p=0.0241). Combining type nonA/nonB with high Entropy defined 20% of patients with significantly shorter DSS (HR 5.3, log-rank p=0.0019). In multivariate analysis, type nonA/nonB and high risk FLIPI score were significant (p=0.038 and 0.035, respectively), while high Entropy trended with inferior DSS (HR 2.8, 95% CI 0.76-10; p=0.123). Taken together, these data support that CyTOF-defined phenotypic subtypes of FL and intratumoral phenotypic diversity identify clinically significant subgroups at initial diagnosis and compare favorably against FLIPI score in predicting both risk of transformation and inferior DSS. [Display omitted] DisclosuresFreeman: Incyte: Honoraria; Seattle Genetics: Honoraria; Sanofi: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Amgen: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria; Teva: Research Funding; Abbvie: Honoraria; Roche: Research Funding. Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Savage: BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; Roche: Research Funding; Servier: Consultancy, Honoraria; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Craig: Bayer: Consultancy. Scott: Abbvie: Consultancy; AstraZeneca: Consultancy; Incyte: Consultancy; Celgene: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling–licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Rich/Genentech: Research Funding; Janssen: Consultancy, Research Funding. Steidl: Trillium Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy; Seattle Genetics: Consultancy; Curis Inc.: Consultancy; Bayer: Consultancy; Epizyme: Research Funding.

The Echelon-2 Trial: 5-Year Exploratory Subgroup Analyses of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Vs CHOP in Frontline Treatment of Pts with CD30-Positive Peripheral T-Cell Lymphoma

The Echelon-2 Trial: 5-Year Exploratory Subgroup Analyses of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Vs CHOP in Frontline Treatment of Pts with CD30-Positive Peripheral T-Cell Lymphoma

Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

High-Dose Methotrexate Is Not Associated with Reduction in CNS Relapse in Patients with Aggressive B-Cell Lymphoma: An International Retrospective Study of 2300 High-Risk Patients

High-Dose Methotrexate Is Not Associated with Reduction in CNS Relapse in Patients with Aggressive B-Cell Lymphoma: An International Retrospective Study of 2300 High-Risk Patients

Updates from Ongoing, First-in-Human Phase 1 Dose Escalation and Expansion Study of TTI-621, a Novel Biologic Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies

Updates from Ongoing, First-in-Human Phase 1 Dose Escalation and Expansion Study of TTI-621, a Novel Biologic Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies

Why was early therapeutic research on psychedelic drugs abandoned?

Advocates of the therapeutic use of psychedelic drugs have argued that a promising approach to treatment was prematurely abandoned in the 1960s primarily because of Richard Nixon's 'War on Drugs'.This paper (1) briefly describes research in the 1950s and 1960s in North America on the use of LSD to treat alcohol dependence, anxiety in terminal illness, and anxiety and depression; and (2) discusses the factors that led to its abandonment. An analysis of historical scholarship on psychedelic research in the 1950s, 1960s and 1970s in North America. Research on psychedelic drugs in psychiatry was abandoned for a number of reasons that acted in concert. A major factor was that clinical research on psychedelic drugs was caught up in the tighter regulation of pharmaceutical research after the Thalidomide disaster in 1963. Psychedelic drugs also presented special challenges for randomised, placebo-controlled clinical trials in the 1970s that were not as positive as the claims made by their advocates in the 1950s and 1960s. Clinical research became more difficult after 1965 when Sandoz ceased providing psychedelic drugs for research and their nonmedical use was prohibited in 1970. The demise of psychedelic drug research was not solely due to the 'War on Drugs'. It was hastened by tighter regulation of pharmaceutical research, the failure of controlled clinical trials to live up to the claims of psychedelic advocates, and the pharmaceutical industry's lack of interest in funding clinical trials.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Revising the model for vaccine development: a step towards tuberculosis immunity

Thanks to accelerated vaccine development, the first COVID-19 vaccine was approved for use by Health Canada only nine months after the disease was declared a pandemic by the World Health Organization [1]. This unprecedented feat was made possible by three critical factors: a stressed sense of urgency, substantial funding, and parallel pre-clinical and clinical trials. Such a concerted effort not only led to the development of multiple effective vaccines, but also bred innovation as mRNA technology bloomed despite its limited use in the past. This success story paves the way for the accelerated development of vaccines for other diseases, such as tuberculosis—the deadliest infectious disease of modern times before COVID-19 emerged.

Reproductive, Obstetrical and Long-Term Health Outcome after Uterus Transplantation: Results of the First Clinical Trial

Background: Uterus transplantation (UTx) is the first available treatment for absolute uterine factor infertility, caused by absence of the uterus or presence of a non-functional uterus. The proof-of-concept of this new fertility treatment was by the world´s first live birth after UTx in 2014. The present study represents the first report on outcome of a complete study cohort undergoing UTx and provides unique data on efficiency and long-term safety of this novel infertility treatment. Methods: We conducted a prospective clinical trial of nine live-donor UTx procedures at Sahlgrenska University Hospital, Gothenburg, Sweden. Seven grafts achieved long-term survival, thereby allowing pregnancy attempts. Hysterectomies were performed within seven years of UTx. The results of in vitro fertilisation, pregnancies, births, growth trajectory of children born, and the long-term medical and psychological health of patients are reported. Findings: Six women delivered nine healthy babies, with three women giving birth twice (cumulative birth rates of 86% in surgically successful transplants and 67% in performed transplants). The clinical pregnancy rate per embryo transfer (ET) was 32.6%. The livebirth rate per ET was 19.6%. Fetal growth and blood flow were normal in all pregnancies. Times of delivery (median in full pregnancy weeks+days (ranges)) by caesarean section and weight deviations were 35+3 (31+6 - 38+0) and -1% (-13% - +23%), respectively. Three women developed preeclampsia during pregnancy and four children acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. The long-term medical health of uterus donors and recipients was generally good. When UTx resulted in a birth, scores for anxiety, depression and relationship satisfaction were reassuring for both donors and recipients. Interpretations: The results of this first clinical UTx trial show that this is an effective infertility treatment for women with absolute uterine factor infertility, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for live donors and graft recipients. Trial Registration: The prospective, observational study “Uterus transplantation from live donors” was registered as a clinical trial (NCT 01844362) Funding: Jan and Dan Olsson Foundation for Science, Knut and Alice Wallenberg Foundation, Swedish Research Council. Declaration of Interest: None of the authors have any conflict of interest. Ethical Approval: This study was approved by the Regional Ethics Committee of Gothenburg, Sweden (#88-12).

Compliance With Vaccination Recommendations Among Patients With Multiple Myeloma: A Real World Experience.

Compliance With Vaccination Recommendations Among Patients With Multiple Myeloma: A Real World Experience.

Practices and Attitudes of Swiss Stakeholders Regarding Investigator-Initiated Clinical Trial Funding Acquisition and Cost Management

Randomized clinical trials (RCTs) are an essential method of evaluating health care interventions and a cornerstone for evidence-based health care. However, RCTs have become increasingly complex and costly, which is particularly challenging for independent investigator-initiated clinical trials (IICTs). IICTs have an essential role in clinical research, and it is important that efforts are made to ensure IICTs are adequately funded and are conducted cost-effectively. To examine the practices and attitudes of Swiss stakeholders regarding IICT funding acquisition and cost management. For this qualitative study, interviews were conducted in Switzerland between February and August 2020. The purposive sample comprised 48 stakeholders from 4 different groups: primary investigators (n = 27), funders and sponsors (n = 9), clinical trial support organizations (n = 6), and ethics committee members (n = 6). Practices and attitudes of stakeholders regarding IICT funding acquisition and cost management were assessed using individual semistructured qualitative interviews. Interviews were analyzed using conventional content analysis. After interviews with 48 IICT stakeholders (75% male presenting), these participants identified a systemic problem of IICTs being underfunded, which can lead to compromises being made regarding the quality and conduct of IICTs. Participants identified 2 overarching and interconnected groups of reasons why IICTs in Switzerland are regularly underfunded. First, it was reported that IICT budget estimations are often inaccurate because of poor planning and preparation, unforeseeable events, investigators intentionally underestimating budgets, and limited budget assessment and oversight. Second, with the exception of a specific IICT funding program by the Swiss National Science Foundation, it was reported that limited funding sources and unrealistic expectation of funders led to underlying challenges in getting IICTs fully funded. A number of measures that could help reduce the underfunding of IICTs were identified, including improving the support of investigators and IICTs, strengthening networking and guidance, harmonizing and simplifying bureaucracy, and increasing public funding of IICTs. This study highlights the inadequate expertise of Swiss stakeholders to correctly, systematically, and reproducibly calculate RCT budgets and the need for transparency on trial costs as well as training in budgeting practices. Limited financial resources for academic clinical research and issues regarding the professional planning and conduct of IICTs are persistent issues that many other countries also face.

Phase III randomized clinical trials global distribution and funding: Trends and disparities.

e18563 Background: Phase III clinical trials (PIIICT) constitute the cornerstone of the progress and development of new therapeutic strategies. However, their complexity and costs in a scenario of limited funding sources impose important limitations in their scope and reach. Methods: We searched in clinicaltrials.gov to identify PIIICT evaluating pharmacological interventions in adjuvant, neoadjuvant and metastatic settings between 2010-2020 in breast, cervix, colorectal cancer (CRC), lung, melanoma, prostate and penile cancer. Trials identified were categorized according to disease site, funding source and world region/country (R/C). Case incidence in 2020 was collected from the IARC website. Results: Of 825 clinical trials, 72.7% were industry-sponsored (IS). Trials by R/C, not including multicentric studies (61.8%): (A) USA 76 trials, 53.9% non-industry sponsored (NIS); (B) Europe/UK 112, 59.8% NIS; (C) Asia (excluding China) 62, 27.4% NIS and (D) China 183, 43.7% NIS. There was a statistically significant association between location and funding source (p= 0.0003). NIS source was detected in higher proportion of trials ongoing in regions A and B (59%). IS was statistically less frequent in uterine cervix/penis (42.8%) and CRC (49.6%) IS was significantly higher in lung and prostate trials (both 81%) (p&lt;0.0001). Table summarizes our results by tumor sites. We also found a statistically significant association between the incidence of malignancies in the selected primary sites and the amount of registered clinical trials, overall (p&lt;0.0001) and IS as well (p&lt;0.0001). The database is under expansion to include other disease sites as well as other geographic areas separately (Africa, Russia, South America, India, and Oceania). Cervix and penile results were combined given their biological and epidemiological similarities. Conclusions: There is a significant disparity between the number of clinical trials and tumor prevalences as well as among the distribution of IS trials funding.[Table: see text]

Infusion Reactions in Persons Receiving the Broadly Neutralizing Antibody VRC01 or Placebo for Reduction of HIV-1 Acquisition: Results From the Phase 2b Antibody Mediated Prevention (AMP) Randomized Trials

Background: The AMP studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are two harmonized Phase 2b randomized controlled trials to assess HIV prevention efficacy and safety of intravenous (IV) infusion of anti-gp120 broadly neutralizing monoclonal antibody (mAb) VRC01. MAbs for other indications elicit significant rates of infusion-related reactions (IRRs), often requiring pre-medication and sometimes limiting their application. We report on IRRs observed in the AMP studies. Methods: From 2016-2018, 2,699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1,901 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or saline placebo. Participants received infusions every 8 weeks (n=10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted pre- and post-infusion and at non-infusion visits. A total of 40,674 infusions were administered. Findings: Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (p<0.01). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (p<0.01) but not in 704/085 (p=0.75). Infusion reactions were associated with atopic history (p=0.01 in 704/085 and p<0.01 in 703/081) and, in 703/081, with younger age at enrolment (p<0.01). Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and “other”. Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. Six (3.8%) IRRs were graded severe, 76 (47.5%) moderate and 78 (48.8%) mild. All reactions were managed successfully without sequelae. Interpretation: IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Laboratory analysis is ongoing to explore the potential mechanisms of these IRRs. Trial Registration: (NCT02716675) (NCT02568215) Funding Information: AI068614, AI068635, AI068618, AI068619, AI069412. Declaration of Interests: NMM, SE, ST, SK, MJ, MRG, MAA, LN, KM RDLG, LC, CK, PA, MMGL have no COI to declare; SRW has received clinical trial funding from Janssen Vaccines. Ethics Approval Statement: The Institutional Review Boards/Ethic Committees of participating CRSs approved the studies, which were conducted under the oversight of the NIAID Data Safety Monitoring Board (DSMB). All participants gave written informed consent in English or a local language of their preference.

Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

BackgroundFinding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research.MethodsIn this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms.ResultsTraditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding.ConclusionsNew funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

Neurofeedback Impact on Chronic Headache, Sleep, and Attention Disorders Experienced by Veterans with Mild Traumatic Brain Injury: A Pilot Study

A good number of veterans while serving in recent combat zones experienced blast injuries resulting in traumatic brain injuries (TBIs), 80% of which were mild (m) with 25%–50% having prolonged postconcussive symptoms (PCSs). Neurofeedback (NFB) has demonstrated a decent degree of efficacy with mTBI PCSs in civilian and veteran populations. Using infra-low frequency NFB, the authors conducted a pilot study to determine the feasibility and initial efficacy with veterans. Because these results were promising, funding for a full clinical trial was subsequently applied for and acquired.

Improving pandemic preparedness through better, faster influenza vaccines

ABSTRACT Introduction. Timely availability of effective influenza vaccine will be critical to mitigate the next influenza pandemic. The mission of Biomedical Advanced Research and Development Authority (BARDA) is to develop medical countermeasures against pandemics, including influenza and other health security threats. Areas covered. Despite considerable gains in pandemic vaccine preparedness since 2009, old and new challenges threaten the pandemic influenza response capabilities of the U.S. Government: insufficient U.S.-based vaccine production, two-dose vaccination regimen, logistically complex adjuvanted formulation, and sustained surge manufacturing capacity despite no commercial market for pandemic vaccines. Although the coronavirus disease 2019 (COVID-19) pandemic has re-exposed these gaps in preparedness and response, previous investments into flexible influenza vaccine technologies proved to be critical to accelerate COVID-19 vaccine development. Expert opinion. BARDA addresses these challenges by implementing a pandemic influenza vaccine strategy with two key goals: 1) accelerating vaccine development and production (faster) and 2) improving vaccine performance (better). This strategy involves an end-to-end approach, including increasing manufacturing and fill-finish capacity; improving release testing speed; and funding clinical trials to improve current vaccine utilization. As demonstrated by the COVID-19 response, continued investments into this pandemic influenza vaccine strategy will further enhance the ability to respond to future emerging pandemic pathogens.

Headache Symptom Versus Headache Disorders: Impact on COVID-19 Survival

Background: COVID-19 has not impacted people or countries uniformly. This disparity has prompted investigations to identify clinical and genetic predictors of COVID-19 mortality. Headache, a COVID-19 symptom, has been associated with positive disease prognosis in small cohorts, but larger confirmatory data-sets are lacking. Moreover, the global predisposition to experience primary headache disorders might be correlated with variances in COVID-19 mortality rates. Methods: We conducted a meta-analysis of studies of COVID-19 inpatient survival that also reported headache as a COVID-19 symptom. Separately, using a generalized additive model regression (GAM), we analysed data across 171 nations to identify variables which impact COVID-19 mortality rates. We performed similar analyses of seasonal influenza mortality. Prevalence data were extracted from the Global Health Data Exchange. Findings: We meta-analysed 48 studies and observed a significantly higher risk ratio of survival (RR:2·178 [1·882-2·520], pInterpretation: Headache as a COVID-19 symptom enhances survival, whereas headache as a primary disorder is more prevalent in nations with higher COVID-19 mortality. Further studies should investigate (1) mechanisms whereby headache is associated with survival from certain viral infections and (2) whether selection pressures from viruses may have contributed to the evolution of primary headache disorders as adaptations.Funding: No funding was receivedDeclaration of Interests: Dr Shapiro has received in the past 12 months financial or editorial compensation as a research consultant for Eli Lilly and Lundbeck. Mr Gallardo reports no disclosures. Dr Caronna reports no disclosures. Dr Pozo-Rosich has received honoraria as a consultant and speaker for: Allergan-AbbVie, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Neurodiem, Novartis and Teva. Her research group has received research grants from Novartis; has received funding for clinical trials from Alder, Amgen, Electrocore, Eli Lilly, Novartis, Teva. She is a trustee member of the board of the International Headache Society and the Council of the European Headache Federation. She is in the editorial board of Revista de Neurologia. She is an editor for Cephalalgia, Headache, Neurologia, Frontiers of Neurology and advisor for The Journal of Headache and Pain. She is a member of the Clinical Trials Guidelines Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company. There are no conflicts of interest in regard to this manuscript.