Guidance For Industry Research Articles

Methods and applications of percentile estimation

ABSTRACT Percentile is ubiquitous in statistics and plays a significant role in the day-to-day statistical application. FDA Guidance for Industry: Assay Development for Immunogenicity Testing of Therapeutic Protein Products (2016) recommends the use of a lower confidence limit of the percentile of the negative subject population as the cut point to guarantee a pre-specified false-positive rate with high confidence. Shen proposed and compared an exact t approach with some approximated approaches. However, the exact t approach might be compromised by computational time and complexity. In this article, we proposed to use a UMOVER method as a potential alternative for percentile estimation for one application to screening and confirmatory cut point determination due to its easy implementation and similar performance to the exact t approach. The applications and performance comparison with different approaches are investigated and discussed. Furthermore, we extended the proposed method for the comparison of the percentile of the test product and percentile of the reference product followed by numerical studies.

Macroscopic Examination of Multiple-Shot Cattle Heads-An Animal Welfare Due Diligence Tool for Abattoirs Using Penetrating Captive Bolt Devices?

Simple SummaryThe most common method of stunning cattle prior to bleeding in an abattoir is a penetrating captive bolt device, which is basically a piston driven forward by expanding gas produced by a blank cartridge. This creates a concussed state in the animal on impact with the skull, followed by penetration to prevent recovery by destroying key parts of the brain. The successful application of this device requires the correct cartridge strength for the species and accurate placement of the device. This paper examines the heads of animals that have received multiple shots in an attempt to ascertain the cause, to provide abattoirs with training material and an investigative tool to reduce the occurrences of multiple shots and reduce the consequent negative effects on animal welfare at slaughter.Ideally, the application of a penetrating captive bolt device to render cattle immediately unconscious prior to slaughter would be 100% effective. Unfortunately, due to various factors this is not always the case. This paper examined, as an initial proof of concept, 12 bovine heads which had received more than one shot from a penetrating captive bolt, collected from various abattoirs within the United Kingdom. The heads were frozen to facilitate splitting on the medial plane to prevent distortion of soft tissue and each sagittal section was examined macroscopically to ascertain if this method could be used to determine the reasons for repeated stun attempts. In 10 out of 12 heads, shot placement was the determining factor, in one other head it was felt that anatomical variation was the reason and the twelfth head demonstrated signs of gun malfunction as the likely cause. This work provides evidence for a larger trial to facilitate the production of guidance for the abattoir industry, the Animal Welfare Officer and regulators on the examination of heads as part of an investigation of failures of a mechanical stunning system and to provide training material for slaughter staff tasked with effectively stunning cattle.

Bioconversion of Flavonoid Glycosides from Hippophae rhamnoides Leaves into Flavonoid Aglycones by Eurotium amstelodami.

The flowering process has been reported to play crucial roles in improving the flavor and efficacy of fermented tea. Hippophae rhamnoides leaves containing many beneficial ingredients are a suitable plant source for tea processing. In this study, we isolated a β-glucosidase-producing fungus Eurotium amstelodami BSX001 from the fermented tea and used Hippophae rhamnoides leaves (HRL) as a substrate to explore the detailed process of bioconversion of some important functional factors. The results show that the contents of total phenolic compounds and flavonoids increased significantly after seven days, especially flavonoid aglycones (e.g., quercetin, kaempferol, and isorhamnetin). Such compounds greatly enhance the antioxidative activity of fermented products. Metabolic analysis of the standard compounds (rutin, quercetin-3-glucoside, kaempferol-3-glucoside, quercetin, isorhamnetin-3-glucoside, isorhamnetin, and kaempferol) further confirmed the effective biotransformation by E. amstelodami. Mechanisms of the bioconversion could be involved in deglycosylation, dihydroxylation, and O-methylation. Our findings expand the understanding of tea fermentation process and provide further guidance for the fermented tea industry.

Patient Reported Outcomes in Metastatic Breast Cancer Studies: Evaluating the Impact of the FDA Guidance for Industry

Introduction: Over the last two decades, a number of new therapies have demonstrated improved overall survival in metastatic breast cancer (MBC) [10]. Despite these advances, MBC remains incurable with a median survival of less than three years [7, 10, 11, 15]. Prolonging survival and maintaining quality of life (QoL) continue to be the central goals of therapy. Unlike the early stages of breast cancer, the management of MBC is less clearly defined, with no specific treatment recognized as the standard of care [15]. Several studies have sought to determine an optimal regimen for the management of MBC with aims to prolong survival, however relatively few adequately powered studies have directly addressed QoL [8]. Patient reported outcomes (PROs) are instruments used to elicit the patient experience thereby gaining insight into a particular health state and aiding in the assessment of QoL [5]. As the prevalence of PROs grew, the FDA released in December 2009 an industry guidance on the implementation of PROs in clinical trials for the development of medical products and to support labeling claims [1]. This study was undertaken with aims to evaluate the impact of the FDA guidance on the use of PROs as standard endpoints in randomized phase two or three clinical trials assessing therapeutic options in MBC. Methods: Clinicaltrials.gov’s advanced search tool was used to capture registered interventional phase two or three clinical trials in adult patients with MBC conducted in the United States that began recruitment between January 1, 2002 and December 31, 2017. Trials with QoL or PROs listed as primary or secondary endpoints on Clinicaltrials.gov were subsequently identified. Segmented regression analysis of the interrupted time series data [18] was used to estimate dynamic changes pre and post adoption of the FDA guidance. Results: A total of 677 studies were identified, 72 of which used PROs. Prior to adoption of the FDA guidance, there is a nonsignificant trend towards increasing PRO use at a rate of 0.4% per year (p > 0.05). At the time of adoption, there is a one-time nonsignificant increase of 0.6% in PRO use (p > 0.05). After adoption, there is a nonsignificant trend towards decreasing PRO use at a rate of 0.3% per year (p > 0.05). Discussion: Our study results demonstrated that despite the FDA guidance, there has been little change in the use of PROs as endpoints in MBC studies. This missed opportunity to elicit the patient experience inherently limits evidence often used to counsel patients and support their decision-making framework as they focus on their priorities in selecting treatment options.

FDA guidance on cardiovascular risk of antidiabetic therapies: One decade later.

The 2008 FDA guidance for industry on cardiovascular (CV) risk of new antidiabetic therapies arose from a history of CV safety concerns brought to a head by findings with rosiglitazone and the ACCORD trial of intensive glycaemic control.

An Assessment of Concerns Regarding New Regulatory Guidance for Combination Products: A Review of the Submissions Made to the FDA Regarding Their Proposed Draft New Guidance on Human Factors Studies for a Combination Product in an Abbreviated New Drug Application.

The US Food and Drug Administration (FDA) put out a call for comments on new draft guidance for industry "Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA." This call for comments elicited 7 submissions from various organizations in the field of health care products. This article reports on a review conducted on these 7 submissions. The purpose of this review was to identify any commonalities across the different submissions and determine if there was consensus on any point or aspect of the draft guidance. To identify any commonalities, a heat map plotting the lines of the draft guidance that had raised a comment/suggestion was produced. Also, a thematic analysis was conducted on the comments/suggestions. In total the 7 submissions produced 137 suggestions. The heat map revealed that these suggestions did not focus on any single part of the guidance but were spread throughout the guidance. The thematic analysis conducted on the suggestions found a number of distinct trends. These trends were grouped into 10 primary themes, each with a number of subthemes. It was concluded that guidance from the FDA on this matter is warranted and would be appreciated. However, it was also concluded that based on the distinct trends identified in the suggestions, there are issues that the FDA may wish to consider before publishing their final guidance.

Wild Goldenseal (Hydrastis canadensis) Rhizome/Root Alkaloid Content in Relation to Colony and Harvest Stage

ABSTRACTThis study examined the three major alkaloids (berberine, hydrastine, and canadine) in wild goldenseal (Hydrastis canadensis) roots and rhizomes in relation to plant colony and harvest stage. Goldenseal colonies in central Pennsylvania, USA, were sampled on four dates (July 2, August 7, September 8, and October 12) corresponding with observable phenological stages between fruit maturity and senescence. Variation was observed for all three alkaloids with berberine and hydrastine present in all colonies and samples, while canadine was not detected during some late season sample dates. Nineteen root samples (53%) met the established United States Pharmacopeia (USP) standards for berberine content, while only one sample (2.8%) met USP standards for hydrastine. All colonies and samples showed an increase in alkaloid levels at the time of senescence, which corroborated the industry guidance that rhizomes/roots should be harvested at senescence (typically during the Fall season). Harvesting at senescence also permits fruit to mature and thereby facilitates sexual reproduction. However, alkaloid levels averaged the second highest at fruit maturity (July 2) which suggested that alkaloids may fluctuate during the growing season in response to, or as a function of, key reproductive events.

Effect of Steaming Processing on Phenolic Profiles and Cellular Antioxidant Activities of Castanea mollissima.

The intention of this study was to investigate the effect of steaming processing on phenolic profiles and antioxidant activities in chestnuts. Steaming processing at different times and temperatures depicted diverse impacts on free and bound fractions. Though, bound phenolics were stable but long time steaming at higher temperatures tended to improve the levels of phenolics, flavonoids as well as antioxidant activities in chestnut kernels, by up to 60.11% of the original value. Seven phenolic compounds including ferulic acid, chlorogenic acid, gallic acid, vanillic acid, syringate, p-coumaric acid and quercetin were found to change during thermal processes. Significant relationships (p < 0.05) were identified between total phenolics and total antioxidant activities. However, the consistency of chlorogenic acid (p < 0.01) only with cellular antioxidant activity indicated poor bio-accessibility of the phytochemicals in chestnuts. However, this situation could be partly improved by steaming. Steaming could improve the cellular accessibility of free phytochemicals, particularly, increasing the bio-accessibility by 41.96%. This study provided valuable information on dynamic changes of phenolic profiles and antioxidant activity of chestnuts under a steaming process, which could offer possible guidance for the chestnut processing industry in the future.

Application of the New York BitLicense to Initial Coin Offerings

Would New York's BitLicense apply to all forms of initial coin offerings, whether issued as protocol tokens, investment tokens, or utility tokens? After discussing the background, regulatory framework, and application of the BitLicense, I conclude that based on the letter of the law, every Person who sells blockchain-based tokens in an ICO, where New York residents are capable of purchasing tokens, are likely regulated by the law. This will probably be true whether the tokens issued serve an investment or utility purpose, but that distinction could make a difference in the future if the regulation’s intended application is relied on in industry guidance or through the New York Department of Financial Services enforcement actions.

Risk-Based Monitoring Approach to Ensure the Quality of Clinical Study Data and Enable Effective Monitoring

Following the Guidance for Industry by FDA, the concept of risk-based approach has spread rapidly in recent years. It facilitates more effective, efficient, and high-quality clinical study execution. We carried out a pilot study that adopted risk-based monitoring. In the preparatory stage, the risks of this study (protocol level and program level) were assessed and mitigated as much as possible. During the study, centralized monitoring were conducted in parallel with site (on-site/off-site) monitoring, and study risks were assessed based on the results of both monitoring in accordance with the risk management plan. We found that average on-site monitoring frequency decreased as the study progressed. After study completion, we conducted a Pharmaceutical and Medical Devices Agency inspection but found no significant nonconformance that would have affected the study results and patient safety. The results indicate that a risk-based approach, which is an innovative monitoring approach, contributes to the reliability of study results and promotes efficient monitoring.

Establishing pre-clinical pharmacokinetic parameters for drug candidate using targeted mass spectrometry

Event Abstract Back to Event Establishing pre-clinical pharmacokinetic parameters for drug candidate using targeted mass spectrometry Norazwana Samat1*, Wai Mun Kong2, Noreena Nordin2, Atiqah Tahziz2, Zamri Chik2 and Pei Jean Tan1 1 Cancer Research Malaysia, Malaysia 2 Faculty of medicine, University of Malaya, Malaysia Background Preclinical evaluation of drug candidate is important in the overall drug discovery process, mainly to address not only safety and efficacy but also the pharmacokinetics of a drug candidate. Pharmacokinetics studies the time course of drug absorption, distribution, metabolism and excretion. Liquid chromatography coupled with tandem quadrupole mass spectrometry (LC-TQMS) has been widely used as a tool to study pharmacokinetics, offering sensitive detection on wide dynamic range and selectivity on target molecules by multiple-reaction monitoring, which is critical for targeted quantification of candidate drugs in vivo. Methods To accurately quantify plasma level of our drug candidate, we adopted LC-TQMS as our tool. We first introduced our anti-cancer drug hit, ADF into LC-TQMS for optimal detection. Next, the optimized method was validated according to the ‘Bio-analytical method validation – Guidance for Industry’ from US-FDA, on the aspect of selectivity, accuracy, precision, recovery and stability of ADF. Following, calibration curves were generated and rat blood samples were collected at specific time points after intraperitoneal administration. Concentration of ADF in rat was quantified based on calibration curve. Pharmacokinetic parameters such as half-life, clearance and area under curve were determined using non-compartmental analysis. Results From our analysis, ADF was detected optimally in negative ionization mode at transition of m/z 491.1 -> 217.2 and using Luna HILIC 3 µm particle size, 150 x 2.0 mm column for analytical separation. Calibration curve was generated over concentration range of 20 to 250 ng/mL with r2 = 0.99. Intra- and inter-day precision and accuracy was achieved as per guideline with <15% coefficient of variation. The overall pharmacokinetics properties of ADF is currently under investigation. Conclusion The state of the art for accurate quantification of drug candidates for the determination of pharmacokinetic properties has been established. Findings from this study have provided necessary guidance for lead optimization in the drug development process. Keywords: pharmacokinetic, pre-clinical, Mass spectometry, Drug Discovery, Drug candidate Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Miscellaneous Citation: Samat N, Kong W, Nordin N, Tahziz A, Chik Z and Tan P (2019). Establishing pre-clinical pharmacokinetic parameters for drug candidate using targeted mass spectrometry. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2019.63.00030 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Nov 2018; Published Online: 17 Jan 2019. * Correspondence: Mrs. Norazwana Samat, Cancer Research Malaysia, Subang Jaya, Malaysia, norazwana.samat@cancerresearch.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Norazwana Samat Wai Mun Kong Noreena Nordin Atiqah Tahziz Zamri Chik Pei Jean Tan Google Norazwana Samat Wai Mun Kong Noreena Nordin Atiqah Tahziz Zamri Chik Pei Jean Tan Google Scholar Norazwana Samat Wai Mun Kong Noreena Nordin Atiqah Tahziz Zamri Chik Pei Jean Tan PubMed Norazwana Samat Wai Mun Kong Noreena Nordin Atiqah Tahziz Zamri Chik Pei Jean Tan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

FDA position statement “Early Alzheimer's disease: Developing drugs for treatment, Guidance for Industry”

Despite billions of dollars invested in clinical trials to develop novel therapeutics for Alzheimer's disease, no approved treatments have been developed in the past 15 years. In that span, new classes of drugs have been developed and tested, including monoclonal antibodies, γ-secretase modulators, γ-secretase inhibitors, BACE inhibitors, RAGE inhibitors, nicotinic agonists, 5HT6 antagonists, and others. The one constant for all of these clinical trials programs is the use of the ADAS-cog as the primary scale to determine efficacy. The question that needs to be considered is whether it is the target engagement of the drug or the clinical trial measure testing the efficacy. The FDA put out a new position statement in 2018 informing the field on possible considerations for demonstrating efficacy to open the path for approval. Here, we propose and comment on a variety of approaches that are alternatives to the ADAS for FDA-specified stage 3 and 4 Alzheimer's disease. These novel outcomes are being validated in current clinical trials and could be used as efficacy measures moving forward.

Challenges and Response to the Development of Sharing Economy in Dazhou

The development of sharing economy activates the stock resources of Dazhou, improves the employment rate of Dazhou, and protects the environment of Dazhou. To promote the healthy development of sharing economy in Dazhou, we should further popularize the concept of sharing economy, strengthen industry supervision and guidance, innovate the supervision thinking, increase the government support for sharing economy, provide support for the development of sharing economy platforms in policies and funds, and create a good environment for the development of sharing economy.

Research on Improvement of Truck Vibration Based on Systematic G8D Method

In view of the common and difficult to solve vehicle vibration problem, taking a large truck manufacturing enterprise in China as an example, an improved model for solving truck vibration problem is established by using the G8D method, and the unbalanced excitation force of the wheel system is analysed. The coupling of the excitation frequency and the natural frequency of the system leads to the resonance phenomenon, as well as the inadequate damping function of the system, is the fundamental cause of the vibration problem. After verifying and implementing permanent correction measures at the same time at the three levels of components, devices, and the entire vehicle, the acceleration of the seat guide rails for the vibration performance of the truck reduces from the original state 1.04 m/s2 to 0.6 m/s2, a decrease of 42.3%, which reaches the best level of mainstream cars in the country and is close to the optimal level of 0.5 m/s2 among the same kinds of cars in Germany. Therefore, the improved model can improve the sustainability of product manufacturing, provide industry guidance for solving the quality problem of truck vibration, and provide a sustainable guarantee for social public transport safety.

The Research on the Government Industry Guidance Fund Performance Evaluation

Government-led fund is an effective way to market the financial support and can become an important equity financing channel for emerging industries. At present, the operation mechanism of the domestic government-led fund is not perfect, and the performance evaluation system needs to be established and perfected. The basic principle of government-led fund performance evaluation should be conducive to improving the efficiency of fund operation, guiding the flow of funds to the key areas and weak links of emerging industries, and regulating the behavior of fund management subjects. The performance evaluation system of government-led fund is composed of three major indicators: policy objective, management level and economic benefit.

Research on Risk Management and Optimization of Government Industry Guidance Fund

As an innovative tool to leverage social capital and improve the efficiency of fiscal funds utilization, the government industry guidance fund entered the stage of rapid development under a series of favorable policies in China. But at the same time, there still exist many potential risks in its operation. How to identify and control these risks needs to be explored and summarized in theory and practice. This paper will analyze a series of risks and put forward optimization suggestions for risk management in the operation of government industry guidance fund.

Spectrofluorimetric determination of eptifibatide in human plasma and dosage form.

A spectrofluorimetric method for the determination of eptifibatide is presented based on its native fluorescence. The type of solvent and the wavelength of maximum excitation and emission were carefully selected to optimize the experimental conditions. Under the specified experimental conditions, the linearities obtained between the emission intensity and the corresponding concentrations of eptifibatide were in the range 0.1-2.5μg/ml for the calibration curve constructed for direct determination of eptifibatide in dosage form and 0.05-2.2μg/ml for the calibration curve constructed in spiked human plasma with a good correlation coefficient (r>0.99). The lower limit of quantification for the calibration curve constructed in human plasma was 0.05μg/ml. Recovery results for eptifibatide in spiked plasma samples and in dosage form, represented as mean±% RSD, were 95.17±1.94 and 100.29±1.33 respectively. The suggested procedures were validated according to the International Conference on Harmonization (ICH) guidelines for the direct determination of eptifibatide in its pure form and dosage form and United States Food and Drug Administration (US FDA) Guidance for Industry, Bioanalytical Method Validation for the assay of eptifibatide in human plasma.

New Criteria for Safety Distances During Pneumatic Pressure Testing of Vessels and Pipes

The industrial gas and liquefied natural gas (LNG) industries routinely perform equipment pressure testing pneumatically, rather than hydraulically, due to the necessity for keep piping and equipment dry. Hazards associated with potential failure of pneumatically pressurized equipment under test are well understood, but today, there is no commonly recognized industry guidance on recommended safety distances to protect personnel during such tests. Air Products, Air Liquide and BakerRisk have worked together to develop such guidance for the testing of vessels, process pipes and pipelines, and present in this article new, simple to use correlations, with results also presented in the form of lookup tables. These new correlations are based on the application of established methods, validated against previously published independent test data and new test data presented here for the first time. © 2018 American Institute of Chemical Engineers Process Saf Prog 38: e12025, 2019

Cutting performance of cemented carbide cutting tool in turning high‐density fiberboard

AbstractIn order to provide a scientific and reliable guidance for wood processing industry, the effects of cutting parameters on cutting forces, cutting temperature and tool wear were studied when turning high‐density fiberboard by use of cemented‐carbide cutting tools. The results showed that cutting forces (normal force and radial force) and cutting temperature are not affected by the cutting parameters in the same way: cutting forces decrease with increasing spindle speed, whereas cutting temperature increase with an increase of the spindle speed. However, there is a positive relation for cutting forces and temperature, to the feed per turn when cutting. The wear of the cemented‐carbide cutting tool is shown by two mechanisms: Mainly adhesive wear but also abrasive wear, showed by loss of carbide‐grains and by cracking and chipping, respectively. This study also indicated that higher‐speed cutting is beneficial for wood‐processing; evident by reduced energy for cutting and higher efficiency in production.

Using Social Media to Highlight Unmet Needs in Patients with AML and MDS Ineligible for Intensive Chemotherapy: A Patient Centered Perspective

Objectives: For patients with AML/MDS who are ineligible for intensive chemotherapy, prognosis is poor and effective treatment options are limited, often leading to unmet medical needs in this population. A deeper understanding of the patient perspective in this population is valuable to inform decision making and better address patients' needs. The FDA encourages the use of social media to shed light on patients' perspectives regarding the symptoms and impacts of their disease, stressing the opportunity to inform medical product development and enhance regulatory decision making.[i] This study aimed to use social media data to identify self-reported barriers to treatment, and capture the patient/caregiver understanding of the condition and prognosis in AML/MDS patients ineligible for intensive chemotherapy.Methods: AML and MDS patient/caregiver posts were extracted from publicly available discussions on three large AML/MDS specific forum sites. User posts were manually reviewed to only include the experience of patients ineligible for intensive chemotherapy. A total of 1,443 posts from 220 AML patients/caregivers and 2,733 posts from 127 MDS patients/caregivers were included. A manual qualitative review of a sample of 80 AML patients/caregivers and 5 MDS patients/caregivers' posts was conducted. Hypothesis coding was used to develop a coding dictionary based on key themes and open coding was used to incorporate additional themes, codes, and sub-codes inductively. Relevant content was coded, grouped into categories and overall themes.Results: Of the 85 user posting histories reviewed, 73 (86%) contained relevant information about the stated key objectives: 41 (56%) of users discussed factors relating to treatment decisions and 37 (51%) discussed unmet needs. The most common reasons for why the patient received no treatment were: the patient could not cope with chemotherapy due to co-morbidities or poor heath (31%), old age (26%), lack of effective available treatment options (18%) and the risk of side effects (15%). Other reasons included wanting to travel and adverse events. The most commonly reported unmet needs were: lack of/no treatment options (23%), lack of information about prognosis and deterioration (18%), lack of information about treatment (13%), lack of understanding about the condition (8%) and a lack of support and information from doctors (8%). Other unmet needs discussed included delayed diagnosis, treatment effectiveness, and lack of family support.Discussion: The need for more effective treatments in this population is known. However, this analysis shows patients/caregivers also face additional challenges. The discussion surrounding lack of information about prognosis, deterioration and treatment suggest there is a communication barrier between patients/caregivers and clinicians. Patients/caregivers expressed that they did not receive adequate information about these topics. It is not possible to determine whether the information was not given or whether patients/care givers failed to understand information that was given. Clinicians need ensure these topics are discussed, and delivered in a manner comprehensible for patients/caregivers to help patients make more effective treatment decisions. Furthermore, a greater understanding of AML and its symptoms is required to potentially allow for earlier diagnosis.[i] United States Food and Drug Administration (FDA). June 2018. Patient-Focused Drug Development: CollectingComprehensive and Representative Input Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders. Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM610442.pdf [accessed July 24, 2018]. DisclosuresBooth:Evidera: Employment. Bell:Pfizer: Employment, Equity Ownership. Halhol:Evidera: Employment. Pan:Evidera: Employment. Welch:Pfizer: Employment, Equity Ownership. Merinopoulou:Evidera: Employment. Lambrelli:Evidera: Employment. Cox:Evidera: Employment.