Industry-sponsored Clinical Trials Research Articles

Physician compensation for industry-sponsored clinical trials in multiple sclerosis influences patient trust

BackgroundPerceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust. ObjectiveTo understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials. MethodsAn anonymous online instrument was developed. Results597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials. ConclusionsResults of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust.

Justification for conducting neurological clinical trials as part of patient care within private practice.

The aim of this review was to assess the benefits and drawbacks of conducting neurological clinical trials and research in private practice for the patients, clinician, Practice Manager, sponsors/Clinical Research Organisations (CROs) and Clinical Trial Coordinator (CTC) to determine if this is justified for all involved. A combination of literature reviews, original research articles and books were selected from 2005 to 2015. Provided that the practice has sufficient number of active trials to prevent financial loss, support staff, adequate facilities and equipment and time, the benefits outweigh the drawbacks. Clinical trials provide patients with more thorough monitoring, re-imbursement of trial-related expenses and the opportunity to try an innovative treatment at no charge when other options have failed. For the clinician, clinical trials provide more information to ensure better care for their patients and improved treatment methods, technical experience and global recognition. Trials collect detailed and up-to-date information on the benefits and risks of drugs, improving society's confidence in clinical research and pharmaceuticals, allow trial sponsors to explore new scientific questions and accelerate innovation. For the CTC, industry-sponsored clinical trials allow potential entry for a career in clinical research giving CTCs the opportunity to become Clinical Research Associates (CRAs), Study Start-Up Managers or Drug Safety Associates.

Characteristics of NIH- and industry-sponsored head and neck cancer clinical trials.

Compare U.S. clinical trials sponsored by the National Institutes of Health (NIH) and industry, especially with regard to trial design, interventions studied, and results reporting rates. U.S. head and neck cancer clinical trials. We used information from ClinicalTrials.gov to compare NIH- and industry-sponsored head and neck cancer clinical trials, specifically analyzing differences in trial design and interventions studied. We examined publication rates and positive results rates using PubMed.gov. About 50% of NIH- and industry-sponsored clinical trials have their results reported in peer-reviewed literature. Industry-sponsored trials had higher rates of positive results than NIH-sponsored trials. NIH- and industry-sponsored clinical trials had similar trial designs, although industry-sponsored trials had significantly lower rates of randomization. Industry trials utilized radiation in 19% of trials and surgery in 2% of trials. NIH trials also had low utilization of both radiation and surgery (27% and 12% of trials, respectively). NIH- and industry-sponsored trials published their results in journals with comparable impact factors. There is significant underreporting of results in U.S. head and neck cancer clinical trials, whether sponsored by NIH or industry. Industry trials have significantly higher rates of positive results, although it is unclear what contributes to this. Both NIH- and industry-sponsored trials underutilize surgery and radiation as treatment modalities, despite the fact that these are standard-of-care therapies for head and neck cancer. We recommend that the NIH and industry report all results from clinical trials and use surgery and radiation as treatment arms in order to arrive at more balanced therapeutic recommendations. N/A. Laryngoscope, 126:E300-E303, 2016.

Activating clinical trials: a process improvement approach.

BackgroundThe administrative process associated with clinical trial activation has been criticized as costly, complex, and time-consuming. Prior research has concentrated on identifying administrative barriers and proposing various solutions to reduce activation time, and consequently associated costs. Here, we expand on previous research by incorporating social network analysis and discrete-event simulation to support process improvement decision-making.MethodsWe searched for all operational data associated with the administrative process of activating industry-sponsored clinical trials at the Office of Clinical Research of the University of South Florida in Tampa, Florida. We limited the search to those trials initiated and activated between July 2011 and June 2012. We described the process using value stream mapping, studied the interactions of the various process participants using social network analysis, and modeled potential process modifications using discrete-event simulation.ResultsThe administrative process comprised 5 sub-processes, 30 activities, 11 decision points, 5 loops, and 8 participants. The mean activation time was 76.6 days. Rate-limiting sub-processes were those of contract and budget development. Key participants during contract and budget development were the Office of Clinical Research, sponsors, and the principal investigator. Simulation results indicate that slight increments on the number of trials, arriving to the Office of Clinical Research, would increase activation time by 11 %. Also, incrementing the efficiency of contract and budget development would reduce the activation time by 28 %. Finally, better synchronization between contract and budget development would reduce time spent on batching documentation; however, no improvements would be attained in total activation time.ConclusionThe presented process improvement analytic framework not only identifies administrative barriers, but also helps to devise and evaluate potential improvement scenarios. The strength of our framework lies in its system analysis approach that recognizes the stochastic duration of the activation process and the interdependence between process activities and entities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1227-2) contains supplementary material, which is available to authorized users.

Shackling Innovation the Regulation of Industry Supported Clinical Trials

Over the past three decades, collaborative arrangements between academic biomedical researchers and private industry have grown dramatically, resulting in medical innovations that have benefi ted society greatly. However, a growing chorus of criticism directed at private companies that sponsor and conduct biomedical research casts doubt on the very ethos of science. Academics and anti-business activists have waged a campaign against industry-sponsored clinical trials that denies the fundamentally commercial nature of such research and hinders medical progress. These critics point to a small number of unfortunate and tragic cases in which fi nancial confl icts of interest may have played a role in research-related injuries and deaths in order to unjustifi ably condemn the profi t motive in biomedical research as a whole.The debate over confl icts of interest, once confi ned to the pages of medical journals, has jumped aboard a runaway train. In response to public outcry, the Obama administration and the 111th Congress have promised stronger federal regulation and a far more aggressive role for federal and state governments in the nation’s biomedical economy. Industry critics, however, are pushing for even stricter regulations, including the abolishment of industry-sponsored clinical trials all together. Prohibition or even greater regulation of industry sponsorship makes no sense. Given the paucity of evidence linking fi nancial confl icts of interest to research-related mishaps, these new regulations elevate isolated incidents to the norm, and confuse correlation with causation. The way to prevent dangerous or ineffective drugs from reaching the market is not to eliminate fi nancial incentives, but quite the opposite—to make well-conducted successful research so rewarding, both fi nancially and otherwise, and errors in research so costly, that the only logical choice for researchers is to do their absolute best to produce accurate results. If the profi t motive is removed, so is the most immediate benefi t of doing good work and the long-term cost of doing poor work. The net result of policies that restrict industry sponsored clinical trials will be a slowing of medical advances and a delay in the development and marketing of new medical technologies that have the potential to save thousands of lives. Suggestions for restricting fi nancial incentives are being made without any clear evidence, let alone proof, that doing so will prevent the tragic incidents that fuel today’s movement to restrict industry-sponsored clinical trials. After a careful analysis of both the facts and the arguments for and against restricting industry-sponsored clinical, we suggest that regulators should be moving in a totally different direction. Educating people about drug development, clinical trials, risks and benefi ts, and fi guring out ways to increase compliance with medical instructions is likely to go much further toward reducing adverse reactions to medications than trying to eliminate confl icts of interest.

Patient-Reported Outcomes in Metastatic Breast Cancer: A Review of Industry-Sponsored Clinical Trials.

INTRODUCTIONPatient-reported outcome (PRO) measures serve to capture vital patient information not otherwise obtained by primary study endpoints. This paper examines how PROs are utilized as endpoints in industry-sponsored metastatic breast cancer clinical trials.METHODSA search was conducted in the clinicaltrials.gov web site for trials involving common treatments for metastatic breast cancer. Thirty-eight clinical trials were identified which included a PRO endpoint in the study, and data were extracted and summarized.RESULTSOverall, 17 unique PRO questionnaires and 14 concepts of measurement were identified as secondary or exploratory endpoints. The Functional Assessment of Cancer Therapy—Breast was the most frequently utilized questionnaire, commonly implemented to assess quality of life. The EORTC QLQ-C30 was also frequently used to measure quality of life or pain.CONCLUSIONThis review shares insights into the role of PROs in trials for metastatic breast cancer from which treatment developers and other stakeholders can enhance successful implementation of the patient voice into future trials.

Issues and promise in clinical studies of botanicals with anticonvulsant potential.

Botanicals are increasingly used by people with epilepsy worldwide. However, despite abundant preclinical data on the anticonvulsant properties of many herbal remedies, there are very few human studies assessing safety and efficacy of these products in epilepsy. Additionally, the methodology of most of these studies only marginally meets the requirements of evidence-based medicine. Although the currently available evidence for the use of cannabinoids in epilepsy is similarly lacking, several carefully designed and well controlled industry-sponsored clinical trials of cannabis derivatives are planned to be completed in the next couple of years, providing the needed reliable data for the use of these products. The choice of the best botanical candidates with anticonvulsant properties and their assessment in well-designed clinical trials may significantly improve our ability to effectively and safely treat patients with epilepsy. This article is part of a Special Issue entitled "Botanicals for Epilepsy".

An Estimate of the Benefit-Cost Impact of the FDA Guidance on Data Monitoring Committees.

There is little information available about the impact that FDA guidances have on the clinical trial enterprise. To estimate the impact of the FDA's Guidance for Industry, "The Establishment and Operation of Clinical Trial Data Monitoring Committees for Clinical Trial Sponsors." An economic model was developed to measure the costs and potential savings associated with the change in data monitoring committee (DMC) usage since issuance of the DMC guidance for industry-sponsored clinical trials. To establish the change in use following the issuance of the DMC guideline, a literature search was conducted among high-impact medical journals during publication year 2010 and compared to a similar analysis conducted during publication year 2000. Costs were obtained for DMCs and applicable clinical trials. The results were applied to an analysis of ClinicalTrials.gov completed trials during 2007 to 2013. Review of 4200 manuscripts from publication year 2010 was compared to a similar literature search of publication year 2000. The mention of DMCs in industry-sponsored randomized controlled trials from high-impact journals increased from 24% to 47% (risk ratio = 1.9, P < .0001). This increased rate of DMCs is associated with an increase of 1045 DMCs for industry-sponsored phase 2 and 3 interventional trials that were commenced and completed from 2007 to 2013 and were listed in ClinicalTrials.gov . The increased cost due to these additional DMCs was approximately US$231 million, and the savings associated with early termination of clinical trials due to these DMCs was approximately US$428 million. The DMC guidance has had a net positive economic impact on the clinical trial enterprise. However, noneconomic factors need to be evaluated. ClinicalTrials.gov could be further leveraged to explore further noneconomic benefits and costs of DMCs.

Early results from a multi-component French public-private partnership initiative to improve participation in clinical research - CeNGEPS: a prospective before-after study.

BackgroundA public-private (51/49 %) partnership was initiated in 2007 in France to improve the attractiveness of French sites in industry-sponsored international clinical trials. This initiative developed and implemented a combination of structuring actions and support actions. Here we report the assessment of the impact after 6 years on participation of French study sites in industry-sponsored clinical trials.MethodsWe performed a prospective before-after study of clinical research activities in French public hospitals to assess the impact of actions developed and implemented by CeNGEPS. The programme involved a combination of structuring actions (establishment of sites of excellence, national networks and dedicated clinical research assistants (CRAs)), support actions (tools, templates and training) and competitive budget allocation for sites or networks based on performance. The impact was assessed using the following performance criteria: 1) reduction of the delay to contract signature to ≤ 60 days for 80 % of the trial sites; 2) inclusion of ≥80 % of the planned number of patients by at least 80 % of trial sites; 3) closure of <15 % of trials sites without patients enrolled.ResultsIn 2013, the median delay to contract signature was: 55 days, compared with 76 days in 2008 (27.6 % reduction), 50.5 % of all sites and 58 % of sites with a dedicated CRA included ≥80 % of the planned number of patients compared with 44.8 % in 2008 (12.7 % increase) and 21.3 % of all sites and 9 % of sites with a dedicated CRA closed with no patients included, compared with 26.4 % in 2008 (19.3 and 65.9 %, respectively).ConclusionsThese results provide evidence that it is possible to improve a country’s attractiveness for industry-sponsored clinical research. The two main actions, i.e. establishing sites of excellence throughout the country with well-trained, dedicated staff and establishing a national network of clinical investigators, could be adapted to other countries in Western Europe to improve Europe’s attractiveness to industry-funded trials.

Abstract P4-18-03: IBCSG BIG 1-98 study: The long-term follow-up experience

Abstract Background Industry-sponsored clinical trials often have duration of patient follow-up that is defined according to regulatory requirements. However, in diseases such as endocrine-responsive, early breast cancer, recurrences occur after protocol follow-up, and monitoring of long-term toxicity is important. It is challenging to continue patient follow-up after industry sponsorship ends. Transferring responsibility for additional follow-up to the participating academic centers is required. One such example is the long-term follow-up (LTFU) of patients in the Breast International Group (BIG) 1-98 Trial. We present the procedures and current status of the BIG 1-98 LTFU protocol. Methods In 2010, the BIG 1-98 trial embarked on a new LTFU protocol to gather data on patient outcomes for an additional five years after study completion (2011-2015). Industry sponsorship ceased at the end of 2010. The LTFU study is designed as an observational, non-interventional study to continue the collection of simplified and updated data on survival, disease status, and long-term adverse events from centers participating in the 4-arm option. The International Breast Cancer Study Group (IBCSG) is sponsoring BIG 1-98 LTFU, and per case reimbursement is available. Results The potential BIG 1-98 LTFU cohort consists of the 148 academic medical centers that participated in the 4-arm option with a maximum of 6843 patients enrolled to the parent study. In May 2014, approximately 3 years after initiation of the LTFU protocol, 96 centers had agreed to participate, of which 67 sites had activated the protocol and submitted LTFU data; 31 additional centers were not participating, and the status of 21 centers was unknown. Participation StatusNumber of CentersPatients Enrolled in BIG 1-98Closed317Not Participating28643No response/Unknown21850Yes, participating965333 Activated674215Not Activated291118Totals1486843 Because the original BIG 1-98 informed consent indicated life-long follow-up, only three countries required patient re-consent in order to participate. At least one LTFU data submission has occurred for 73% of patients participating in the LTFU (May 2014). Conclusion Long-term follow-up for a large-scale clinical trial is feasible, but challenging. The methods used for BIG 1-98 LTFU will be described and the status will be updated at the meeting. Citation Format: Anita Giobbie-Hurder, Beat Thürlimann, Bent Ejlertsen, Patrick Neven, Robert E Coleman, Ian Smith, Andrew M Wardley, István Láng, Marco Colleoni, Marc Debled, John F Forbes, Karen N Price, Meredith M Regan, Manuela Rabaglio, Aron Goldhirsch, Alan S Coates, Richard D Gelber. IBCSG BIG 1-98 study: The long-term follow-up experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-18-03.

Patient Perspectives on Physician Compensation and Conflict of Interest in Industry-Sponsored Clinical Trials for Multiple Sclerosis (P7.325)

Patient Perspectives on Physician Compensation and Conflict of Interest in Industry-Sponsored Clinical Trials for Multiple Sclerosis (P7.325)

Patient perspectives on physician conflict of interest in industry-sponsored clinical trials for multiple sclerosis therapeutics

Background: Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices. Objective: To understand attitudes of patients with multiple sclerosis concerning disclosure of potential physician–industry conflicts of interest created by clinical trials and how such disclosures may influence study participation Methods: An anonymous online instrument was developed. Results: 597 people with multiple sclerosis participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence patients’ decisions to participate in these studies. Conclusions: Findings from this study support a call for uniform guidelines regarding disclosure of physician–industry relationships to prospective research participants for industry-sponsored clinical trials.

Psychometrics: Essential for Valid, Reliable, and Responsive Measurement in the Development of Patient-reported Outcome Instruments in Plastic Surgery.

Disclosure: The BREAST-Q and FACE-Q is owned, in part, by Memorial Sloan-Kettering Cancer Center (MSKCC). Based on MSKCC inventor-sharing policy, Dr. Pusic receives a portion of licensing revenues when the BREAST-Q or FACE-Q is used in industry-sponsored clinical trials. Neither of the other authors has any financial disclosures. The Article Processing Charge was paid for by the authors.

Association Between Clinical Measures and Florbetapir F18 PET Neuroimaging in Mild or Moderate Alzheimer’s Disease Dementia

Clinical diagnosis of Alzheimer's disease (AD) is challenging, with 20% or more of patients misdiagnosed, even by expert clinicians. The authors conducted a retrospective, cross-sectional analysis comparing baseline neuropsychiatric and other clinical characteristics in 199 expert-diagnosed mild and moderate AD dementia patients participating in industry-sponsored clinical trials of an investigational therapy, where 18% lacked florbetapir positron emission tomography (PET) evidence of AD neuropathology. Significant differences were found only for cognition and ApoE ε4 status, but the large degree of score overlap would preclude using these measures to predict AD misdiagnosis. This study highlights the value of amyloid PET when evaluating patients with seemingly typical AD.

Has the Promise Been Kept?

In November 1965, a landmark article in Science 1 demonstrated that the demineralized extracellular matrix of bone possesses a property that allows it to induce the formation of new bone when implanted into a nonskeletal site, an effect that initially was known as “bone autoinduction.” Certain members of a family of proteins, later known as bone morphogenetic proteins (BMPs), were shown to be responsible for this effect. Twenty-three years later, scientists cloned recombinant human BMP-2 (rhBMP-2) and touted its potential ability to change skeletal surgery. Clinicians and scientists waited with bated breath for the U.S. Food and Drug Administration (FDA) to grant regulatory approval to this protein. In this issue of JBJS Reviews, Hsu reviews the role of rhBMP-2 in spine surgery. The article provides the historical perspective on the development of this recombinant protein and the results of different preclinical and clinical studies that led to its approval and widespread use. However, despite the many clinical success stories that have accompanied the use of …

Tracking the pharmaceutical pipeline: clinical trials and global disease burden.

Aggregate data about pharmaceutical research and development (R&D) tend to examine Phase III trials. Hence, there are few published data about investigational drugs in earlier phases of clinical development that might fail. It is also unclear how well R&D corresponds to disease burden. We track the pharmaceutical pipeline using data from industry publications that provide otherwise unreported information about industry-sponsored clinical trials. The sample includes 2,477 unique drug entities in 4,182 clinical trials. The majority of drugs targeted neoplasms (26.20%), neurological diseases/diseases of the sense organs (13.48%), infectious and parasitic diseases (10.5%), and endocrine, metabolic, nutrition, and immunity disorders (9.45%). Less than 6% of drugs targeted diseases of the circulatory system, which represent the most prevalent causes of global mortality. Detailing the pharmaceutical pipeline, our findings suggest that pharmaceutical development does not adequately address global disease burden. Future research on the under-reported details of Phase I and II clinical trials is needed to understand how the industry operates and how its resource-allocation matches global health concerns.

Current Trends in Globalization of Industry-Sponsored Clinical Trials

Latest trends based upon analysis of biopharmaceutical-sponsored clinical trial (BPCT) sites added to the ClinicalTrials.gov database during the period 2007–12 have been analyzed. When comparing global market share of BPCT sites in regions/countries for the 2007-09 versus 2010-12 period, our data confirm the previously observed trend of loss of share in developed markets (-2.1%), with simultaneous growth in several emerging markets. During this period North America lost 2.6% of global BPCT sites market share and Western Europe lost 1.1% market share. These market share losses among developed bio-pharmaceutical markets were partially offset by the rapid growth of BPCT sites in Japan (1.2%), and Australia and New Zealand (0.3%). During the same period, emerging markets gained 2.1% global market share. Among emerging markets, CEE continues to dominate, demonstrating highest market share gain (1.5%), followed by emerging Asia (0.7%). Latin America experienced flat growth, while sub-Saharan Africa and TMENA (Turkey, Middle East & North Africa) lost 0.08% and 0.02% of global market share respectively from very low starting levels. Despite the observed market share decline, developed markets contribute more than 74% of global BPCT sites. Although all four BRIC countries (Brazil, Russia, India, and China) remained among top 20 countries by BPCT sites market share, only China demonstrated market share growth and global ranking improvement. Similarly, majority of the top 17 pharmemerging markets by biopharmaceutical sales declined both in relative and absolute terms over the two periods, demonstrating that industry product development growth does not necessarily follow product sales growth. Keywords: Access to clinical research, Biopharma-sponsored clinical trials, Clinical trials in developed markets, Clinical trials in emerging markets, Ethics in clinical research, Globalization of clinical research, Industry-sponsored clinical research, Productivity in clinical research, Quality in clinical research, Regional trends in movement of clinical trials, Societal values of industry- sponsored clinical trials.

Digital/cyber nephropathology, clinical and research application

Digital technology marked the first decade of the 21st century with the advent of whole slide imaging (WSI). Thanks to the invention of digital scanners, WSI technology enables the creation and permanent storage of high resolution images from traditional glass slides. The application of digital pathology has recently been explored within the subspecialty of renal pathology for teaching, pathology-based clinical trials, development of new classification systems, and in support to systems biology-based research in a setting of large consortia. Although an initial investment is required, several general advantages can be listed in support of its application, ultimately resulting in a more neutral budget: 1) enables the anywhere-anytime remote access model; 2) permanent storage of glass slides images, which otherwise with time may fade, get lost or broken; 3) allows annotation of specific structures for teaching, consultation, histology-based research or reproducibility studies; 4) archiving; 5) provide full transparency for regulatory agencies during clinical trials or for research protocols; 6) facilitate training of multiple students looking at the same annotated structures, whether in the classroom, during webinar sections or independent review. This presentation will highlight the current status of digital nephropathology applications in training, clinical and molecular research, and industry-sponsored clinical trials.

Defining mesenchymal stromal cells responsiveness to IFN^|^gamma; as a surrogate measure of suppressive potency

Mesenchymal Stromal Cells (MSCs) are being developed as a transfusional product to treat immune and inflammatory disorders. However, results of industry-sponsored randomized clinical trials that have utilized MSC-like cells have not met primary end points of efficacy for treatment of GvHD or inflammatory bowel disease. A better understanding of MSC mechanism of action would best inform future development strategies. MSC's immunosuppressive potential is markedly augmented by licensing by the proinflammatory cytokine, IFNγ. In the present review, we analyze the effect of MSC preparation methods on MSC's responsiveness to IFNγ and immune plasticity. The concept of prelicensing with IFNγ on MSC's immunosuppressive, engraftment and therapeutic potential is also discussed. Rec.6/10/2014, Acc.8/18/2014, pp168-175

Sublingual immunotherapy for aeroallergens: Status in the United States

Sublingual immunotherapy (SLIT) has been used in the treatment of allergic disease for nearly 30 years and is prescribed at least as frequently as subcutaneous immunotherapy (SCIT). Several large U.S. clinical trials using single allergen tablets (grass and ragweed) or extract solution (ragweed) have met their primary clinical efficacy outcome. In December, 2013 the Federal Drug Administration (FDA) Allergenic Products Advisory Committee favorably reviewed two grass tablet product formulations; the FDA usually follows the recommendations of their advisory committees. Industry-sponsored and investigator-initiated aeroallergen SLIT clinical trials conducted in the United States are the focus of this article. To provide a basis for evaluation of this treatment, SLIT mechanisms, pharmacokinetics, efficacy as reported in systematic reviews, and safety are also discussed. Practical considerations of SLIT in the clinical setting are reviewed. These include patient instructions and adherence, which appear to be as poor as SCIT. Estimated treatment costs based on U.S.-licensed allergen extract manufacturers' list prices and doses reported to be effective in studies using U.S.-licensed allergen extracts or the allergen immunotherapy practice parameters are presented. Unmet needs, which include unknown effective dose for many allergen extracts, optimal schedule (daily versus other) and timing of treatment initiation (perennial versus precoseasonal, ≥8 weeks before or just at the start of season), and whether epinephrine autoinjectors should be routinely prescribed for SLIT patients are discussed.