Showing papers in "Therapeutic Innovation & Regulatory Science in 2018"
TL;DR: A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrollment, adherence, and retention may add considerable financial value to patient engagement investment decisions.
Abstract: While patient groups, regulators, and sponsors are increasingly considering engaging with patients in the design and conduct of clinical development programs, sponsors are often reluctant to go beyond pilot programs because of uncertainty in the return on investment. We developed an approach to estimate the financial value of patient engagement. Expected net present value (ENPV) is a common technique that integrates the key business drivers of cost, time, revenue, and risk into a summary metric for project strategy and portfolio decisions. We assessed the impact of patient engagement on ENPV for a typical oncology development program entering phase 2 or phase 3. For a pre-phase 2 project, the cumulative impact of a patient engagement activity that avoids one protocol amendment and improves enrollment, adherence, and retention is an increase in net present value (NPV) of $62MM ($65MM for pre-phase 3) and an increase in ENPV of $35MM ($75MM for pre-phase 3). Compared with an investment of $100,000 in patient engagement, the NPV and ENPV increases can exceed 500-fold the investment. This ENPV increase is the equivalent of accelerating a pre-phase 2 product launch by 2½ years (1½ years for pre-phase 3). Risk-adjusted financial models can assess the impact of patient engagement. A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrollment, adherence, and retention may add considerable financial value. This approach can help sponsors assess patient engagement investment decisions.
82 citations
TL;DR: A review for a regulatory and industry audience of the current state of relevant statistical methods, and of the uptake of these approaches and the opportunities for broader use of historical data in confirmatory clinical trials.
Abstract: The goal of clinical trial research is to deliver safe and efficacious new treatments to patients in need in a timely and cost-effective manner. There is precedent in using historical control data to reduce the number of concurrent control subjects required in developing medicines for rare diseases and other areas of unmet need. The purpose of this paper is to provide a review for a regulatory and industry audience of the current state of relevant statistical methods, and of the uptake of these approaches and the opportunities for broader use of historical data in confirmatory clinical trials. General principles to consider when incorporating historical control data in a new trial are presented. Bayesian and frequentist approaches are outlined including how the operating characteristics for such a trial can be obtained. Finally, examples of approved new treatments that incorporated historical controls in their confirmatory trials are presented.
71 citations
TL;DR: Developing a framework to qualify RW evidence in the context of a particular study purpose and data asset will enable broader regulatory use of RW data for approval of new molecular entities and label changes.
Abstract: There is growing interest in regulatory use of randomized pragmatic trials and noninterventional real-world (RW) studies of effectiveness and safety, but there is no agreed-on framework for assessing when this type of evidence is sufficiently reliable. Rather than impose a clinical trial-like paradigm on RW evidence, like blinded treatments or complete, source-verified data, the framework for assessing the utility of RW evidence should be grounded in the context of specific study objectives, clinical events that are likely to be detected in routine care, and the extent to which systematic error (bias) is likely to impact effect estimation. Whether treatment is blinded should depend on how well the outcome can be measured objectively. Qualification of a data source should be based on (1) numbers of patients of interest available for study; (2) if "must-have" data are likely to be recorded, and if so, how and where; (3) the accessibility of systematic follow-up data for the time period of interest; and (4) the potential for systematic errors (bias) in data collection and the likely magnitude of any such bias. Accessible data may not be representative of an entire population, but still may provide reliable evidence about the experience of typical patients treated under conditions of conventional care. Similarly, RW data that falls short of optimal length of follow-up or study size may still be useful in terms of its ability to provide evidence for regulators for subgroups of special interest. Developing a framework to qualify RW evidence in the context of a particular study purpose and data asset will enable broader regulatory use of RW data for approval of new molecular entities and label changes. Reliable information about diverse populations and settings should also help us move closer to more affordable, effective health care.
59 citations
TL;DR: This work delved into CRISPR-Cas9 from its natural and ortholog origins to its engineered variants and behaviors to present its notable and diverse applications in the fields of biotechnology and human therapeutics.
Abstract: In the last few decades, genomic manipulation has made significant progress as a result of the development of recombinant DNA technologies; however, more often than not, these techniques have been costly and labor intensive. In contrast, recently developed next-generation sequencing (NGS) technologies have provided a cheaper, faster, and easier process to study genomics. In particular, an NGS technique emerged from bacterial CRISPR-associated protein-9 nuclease (Cas9) as a revolutionary method to modify, regulate, or mark specific genomic sequences on virtually any organism. A later adaptation of this bacterial defense mechanism that successfully and permanently edits dysfunctional genes and corrects missing proteins has resulted in a new era for disease genetic engineering. Clinical trials using this technique are already being performed, and the applicability of CRISPR-Cas9 techniques is actively being investigated using in vivo studies. However, the concept of genome correction poses great concerns from a regulatory perspective, especially in terms of security, so principles for the regulation of these methodologies are being established. We delved into CRISPR-Cas9 from its natural and ortholog origins to its engineered variants and behaviors to present its notable and diverse applications in the fields of biotechnology and human therapeutics.
50 citations
TL;DR: A structured review of the extant literature about mHealth apps in pediatric care and quality assessment of selected apps found in commercial app stores concluded Medscape, Skyscape, and iGuideline are the most comprehensive m health apps for HCPs as quick references for pediatric care.
Abstract: Background:Despite the surge in mobile health (mHealth) applications (apps) about pediatric care in commercial app stores, to our knowledge, reviews of the quality of such apps are lacking. Consequ...
41 citations
TL;DR: Examining pediatric extrapolation from 2009 to 2014 evaluating any changes in extrapolation assumptions and the causes for these changes since a prior analysis published in 2011 found that partial extrapolation decreased, whereas use of No and Complete extrapolation noticeably increased.
Abstract: “Complete Extrapolation” of efficacy from adult or other pediatric data, to the pediatric population, is an important scientific tool that reduces the need for pediatric efficacy trials. Dose finding and safety studies in pediatrics are still needed. “No Extrapolation” requires 2 pediatric efficacy trials. “Partial Extrapolation” eliminates the need to conduct 2 pediatric efficacy trials; 1 efficacy or exposure/response study may be sufficient. We examined pediatric extrapolation from 2009 to 2014 evaluating any changes in extrapolation assumptions and the causes for these changes since a prior analysis published in 2011. We reviewed all 157 products with 388 pediatric studies submitted to the FDA from 2009 through 2014. We assessed whether efficacy was extrapolated from adult or other pediatric data and categorized extrapolation as Complete, Partial, or No, and identified the reasons for the changes. Partial extrapolation decreased, whereas use of No and Complete extrapolation noticeably increased. Complete, Partial, or No extrapolations changed from 14%, 68%, and 18% in the 2011 study to 34%, 29%, and 37% respectively in the current study. The changes were mostly due to a better understanding of pediatric pathophysiology, why trials have failed, and improved endpoints. Evolving science and data obtained from clinical trials increases the certainty of extrapolation assumptions and drives decisions to utilize extrapolation. Lessons learned from the conduct of these trials are critical to improving evidence-based medicine. Extrapolation of Efficacy is a powerful scientific tool that streamlines pediatric product development. Increased knowledge and evolving science inform utilization of this tool.
41 citations
TL;DR: Medscape and Skyscape Medical Library are the most comprehensive mHealth apps for general drug information, medical references, clinical score, and medical calculator.
Abstract: Background:Mobile devices and applications (apps) that act as access tools for health care management aid in the improvement of clinical decision making and patient outcomes. However, the tremendou...
38 citations
TL;DR: Pat groups are developing diverse skillsets and acquiring assets to leverage in order to become collaborators with industry and academia on clinical trials, but there are still mindsets to change, and stakeholders need further guidance on operationalizing a new model of clinical trial conduct.
Abstract: Objective:To identify the elements necessary for successful collaboration between patient groups and academic and industry sponsors of clinical trials, in order to develop recommendations for best ...
38 citations
TL;DR: Although some DTC tests are now cleared in the United States, the concern that a learned intermediary is needed for interpretation of results remains, and the regulatory oversight of this market will need to continue to develop to ensure the protection of consumer health and privacy.
Abstract: Regulatory compliance in the direct-to-consumer genetic testing market is highly sophisticated as there are numerous federal, state, and ethical barriers to entry. In 2010, amid an underregulated market, 23andMe sought to do what few companies in the medical industry had attempted before-disregard the guidance and requests of the US Food and Drug Administration. This regulatory strategy effectively destined the company's Personal Genome Service for failure; however, the company changed course and has been granted several regulatory clearances. This exemplifies the importance of a healthy relationship with regulatory agencies, although challenges remain. The DTC industry continues to have a perplexing regulatory framework at both the federal and state level. There are also ethical concerns with the monetization of deidentified genetic health information, as genetic data have an inherent level of identifiability and are not fully protected by the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule in these scenarios. Although some DTC tests are now cleared in the United States, the concern that a learned intermediary is needed for interpretation of results remains. The regulatory oversight of this market will need to continue to develop to ensure the protection of consumer health and privacy.
31 citations
UCB1
TL;DR: The results indicate PLS could play an important role in the patient-physician dialogue, with continued expansion of online platforms and open-access publishing, and it is likely that greater numbers of patients will seek more specialized health-related information in the future.
Abstract: Background:We sought to determine the value and feasibility of developing plain language summaries (PLS) of peer-reviewed articles for patients.Methods:Members of the European Patients Academy on Therapeutic Innovation or UCB Pharma (N = 74) with a diagnosis of chronic disease, as well as a group of randomly selected neurologists in the US (N = 90) participated in online surveys. Two physicians, 5 patients, and 1 caregiver participated in interviews.Results:Patient survey and interview participants reported that they routinely sought health-related information online. Articles in scientific journals were ranked the third most important source in the survey (47%), after general Internet searches (61%) and patient-specific websites (57%). Survey physicians were equivocal in their views; 46% rated PLS as valuable, 46% as neutral, and 8% as not valuable; however, 60% reported they would use them. A predominant theme emerging in patient interviews was the importance of knowledge and the sense of empowerment it...
29 citations
TL;DR: Clinical trials are an important source of safety data that contribute to the totality of safety information available to generate evidence for regulators, sponsors, payers, physicians, and patients.
Abstract: Background:There has been an increased emphasis on the proactive and comprehensive evaluation of safety endpoints to ensure patient well-being throughout the medical product life cycle. In fact, de...
TL;DR: The Tufts Center for the Study of Drug Development and Medidata Solutions Inc analyzed data from 9737 protocols and 130,601 investigative site contracts associated with these protocols to derive updated benchmarks characterizing protocol complexity, indicating that protocol design complexity continues to grow rapidly.
Abstract: The Tufts Center for the Study of Drug Development and Medidata Solutions Inc analyzed data from 9737 protocols and 130,601 investigative site contracts associated with these protocols to derive updated benchmarks characterizing protocol complexity. The results of the study indicate that protocol design complexity continues to grow rapidly. Nearly all phase I, II, and III complexity measures associated with protocol execution increased significantly (eg, P < .0001) from 2001-2005 to 2011-2015. These measures include the number of unique and total procedures performed per patient over the course of a study, the site work effort to administer protocol procedures, the number of study volunteer visits, and the total number of procedures performed per study volunteer visit. The total cost per planned study volunteer per visit also increased significantly (eg, P < .0001) as did the total cost per study volunteer across all planned study visits. Phase I protocols remain the most complex and the most demanding to execute. Phase III protocols have seen the most substantial growth in protocol complexity. Phase IV protocols saw only modest increases in executional complexity during the 10-year time horizon. The implications of the study findings are discussed.
TL;DR: It would be crucial for the MCC to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance.
Abstract: Background:The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures t...
TL;DR: The Division of Applied Regulatory Science is reviewed, highlighting development and validation of biomarkers; novel humanized animal models; translational predictive safety combining in vitro, in silico, and in vivo clinical biomarkers'; chemical and biomedical informatics tools for safety predictions; novel approaches to speed the development of complex generic drugs, biosimilars, and antibiotics; and precision medicine.
Abstract: In 2011, the US Food and drug Administration (FDA) developed a strategic plan for regulatory science that focuses on developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. In line with this, the Division of Applied Regulatory Science was created to move new science into the Center for Drug Evaluation and Research (CDER) review process and close the gap between scientific innovation and drug review. The Division, located in the Office of Clinical Pharmacology, is unique in that it performs mission-critical applied research and review across the translational research spectrum including in vitro and in vivo laboratory research, in silico computational modeling and informatics, and integrated clinical research covering clinical pharmacology, experimental medicine, and postmarket analyses. The Division collaborates with Offices throughout CDER, across the FDA, other government agencies, academia, and industry. The Division is able to rapidly form interdisciplinary teams of pharmacologists, biologists, chemists, computational scientists, and clinicians to respond to challenging regulatory questions for specific review issues and for longer-range projects requiring the development of predictive models, tools, and biomarkers to speed the development and regulatory evaluation of safe and effective drugs. This article reviews the Division's recent work and future directions, highlighting development and validation of biomarkers; novel humanized animal models; translational predictive safety combining in vitro, in silico, and in vivo clinical biomarkers; chemical and biomedical informatics tools for safety predictions; novel approaches to speed the development of complex generic drugs, biosimilars, and antibiotics; and precision medicine.
TL;DR: This review aims to provide an informative review of the regulatory frameworks of medical devices in the United States, Europe, Canada, and Taiwan, with a particular focus on updated regulatory changes in these countries and the current status of global harmonization on medical devices.
Abstract: The medical device industry is an industry dealing with multiple types of products covering a wide range of applications. As the safety and effectiveness of medical devices are vital to human health, the products must be managed by strict regulations according to the different risk levels. A total product life cycle regulatory system including product design, manufacture, premarket gate keeping, and postmarket monitoring is a common framework for medical device regulations. However, the variety and innovativeness of medical devices are challenging the current regulatory frameworks. Hence, the competent authorities responsible for medical devices worldwide keep renewing their regulatory systems to ensure the safety and effectiveness of medical devices. This review aims to provide an informative review of the regulatory frameworks of medical devices in the United States, Europe, Canada, and Taiwan, with a particular focus on updated regulatory changes in these countries and the current status of global harmonization on medical devices.
TL;DR: Developing greater insight into therapeutic area needs, gaining market access, and greater understanding of drug effectiveness were the top measures identified for return on investment for use of RWE.
Abstract: Background:The adoption and use of real-world evidence (RWE) is becoming increasingly important to drug development and patient safety.Methods:The Tufts Center for the Study of Drug Development (CSDD) conducted a benchmark survey of pharmaceutical and biotechnology companies and contract research organizations in a number of areas that support real-world data (RWD) and evidence, including operations and performance areas. Data were gathered on organizational functions, staff, roles and responsibilities, and skill sets required. Also, current and future allocation of budgets and spending were examined as well as return on investment measures. A total of 30 unique companies responded to the survey.Results:Nearly all respondents (29/30 companies) reported that their organizations had an RWE function and most companies indicated that their RWE functions were increasing in size (21 companies). From a postapproval regulatory and labeling perspective, there were two primary areas for company use of RWD to genera...
TL;DR: This paper discusses data sources and analysis considerations for safety signal detection after a medical product is approved for marketing, and discusses the advantages and disadvantages of safety data obtained from passive postmarketing surveillance systems compared to other sources.
Abstract: Safety data are continuously evaluated throughout the life cycle of a medical product to accurately assess and characterize the risks associated with the product. The knowledge about a medical product’s safety profile continually evolves as safety data accumulate. This paper discusses data sources and analysis considerations for safety signal detection after a medical product is approved for marketing. This manuscript is the second in a series of papers from the American Statistical Association Biopharmaceutical Section Safety Working Group. We share our recommendations for the statistical and graphical methodologies necessary to appropriately analyze, report, and interpret safety outcomes, and we discuss the advantages and disadvantages of safety data obtained from passive postmarketing surveillance systems compared to other sources. Signal detection has traditionally relied on spontaneous reporting databases that have been available worldwide for decades. However, current regulatory guidelines and ease of reporting have increased the size of these databases exponentially over the last few years. With such large databases, data-mining tools using disproportionality analysis and helpful graphics are often used to detect potential signals. Although the data sources have many limitations, analyses of these data have been successful at identifying safety signals postmarketing. Experience analyzing these dynamic data is useful in understanding the potential and limitations of analyses with new data sources such as social media, claims, or electronic medical records data.
TL;DR: RWD is an important source of safety data that contribute to the totality of safety information available to generate evidence for regulators, sponsors, payers, physicians, and patients, however, it is important to determine if such data are fit for purpose.
Abstract: Background:Although randomized controlled clinical trials provide necessary information and serve as the basis for regulatory decision making, a significant gap exists between the evidence these tr...
TL;DR: The current thinking on ethical issues of informed consent and decision-making capacity of research participants, compensation for participation and concerns about undue inducement are discussed.
Abstract: In the current epidemic of opioid use disorders, there is both a scientific and ethical imperative to develop effective medical and behavioral treatments for opioid addiction. Research in subject populations with active and ongoing drug addictions bring unique ethical considerations and challenges. Sponsors, researchers, and institutional review board (IRB) members should be familiar with these unique ethical and medical issues as they design, review, and conduct research planned for this population. Issues include those of informed consent and decision-making capacity of research participants, compensation for participation and concerns about undue inducement, forces that threaten the voluntary nature of research participation including the scarcity of available drug treatment programs, and ensuring that participants are aware of and understand risks that may continue after research participation such as increased risk of overdose after research-mandated drug abstinence. This manuscript discusses the current thinking on these issues.
TL;DR: An IDMC is best served by an independent ISRG that will prepare clear, complete, and comprehensible reports, given the complexities of interim data and IDMC requirements.
Abstract: Background:Organizations presenting reports to independent data monitoring committees (IDMCs) should present data in a way that facilitates the ability of the IDMC to make informed judgments about ...
TL;DR: OVTs’ specific safety/toxicity profiles are described and the performance of further clinical trials of OVTs is encouraged to address the most serious challenges anticipated in the development of OVT as a new class of drugs for the treatment of cancer.
Abstract: Oncolytic virus therapy (OVT) represents a new class of therapeutic agents in cancer treatment. The molecular and cellular mechanisms of action of OVTs have been evaluated in nonclinical/clinical phase trials. Various genetically modified viruses have been developed as oncolytic agents, and the first approval of an OVT for clinical use was issued by the US Food and Drug Administration in 2015. In this context, more and more clinical development of OVTs is anticipated in the future. This article provides a risk assessment of OVT based on the safety data obtained from all clinical trials to date using a publicly available database. The most common adverse events (AEs) observed in clinical trials have been infection-related symptoms such as fatigue, chills, fever, and nausea; few serious AEs have been observed, regardless of the kind of virus or transfected genes. In vivo systemic infusion of OVTs demonstrated a high percentage of AEs, but most AEs were manageable using common drugs. This paper describes OVTs' specific safety/toxicity profiles and encourages the performance of further clinical trials of OVTs to address the most serious challenges anticipated in the development of OVTs as a new class of drugs for the treatment of cancer.
TL;DR: An automatic ADE screening system was established for hospitalized patients in Chinese medical institutions and compared with previous studies, combined drug-event alerts and a system-assisted assessment interface performed better than alerts based only on laboratory values.
Abstract: Background:Computerized detection is a promising method for monitoring adverse drug events (ADEs); however, this method is currently in its infancy and is a new area of exploration in China. This s...
TL;DR: Nuclear medicine staff must be aware of the possibility of adverse reaction with radiopharmaceuticals and find time to share this information with the radiophARMacist and the national pharmacovigilance system.
Abstract: Adverse reactions to radiopharmaceuticals are still not reported worldwide. However, the type of reaction may be severe and cause death. A review of the literature was performed using some criteria of a systematic review established by the Cochrane Collaboration. The results showed that there are a large number of adverse reactions to radiopharmaceuticals. Nuclear medicine staff must be aware of the possibility of adverse reaction with radiopharmaceuticals and find time to share this information with the radiopharmacist and the national pharmacovigilance system.
TL;DR: The ease of completing the ADR form and education level are predictive of patient confidence to report ADRs, and these factors should be considered in designing public promotional activities to encourage patient contributions to pharmacovigilance.
Abstract: Many countries incorporate direct patient reporting of adverse drug reactions (ADRs) into their pharmacovigilance systems as patients provide a different insight into drug safety compared to health care professionals. This study aimed to examine public awareness about ADR reporting in Malaysia and patients’ confidence in reporting ADRs. Using a cross-sectional design and convenient sampling, data were collected in public areas within Kuala Lumpur, Malaysia, via face-to-face interview with a structured questionnaire. Multivariate logistic regression analysis was used to identify the significant predictors of patients’ confidence in ADR reporting. Out of 860 consented respondents achieving a response rate of 73.5%, only 69 (8%) were aware of the Malaysian ADR monitoring system. The majority (60%) of the respondents indicated they had the confidence to report ADRs. Multivariate logistic regression analysis revealed that ease in completing the ADR reporting form was the strongest variable predictive of confidence to report ADRs (odds ratio [OR], 18.45; 95% confidence interval [CI], 10.55-32.25). Increased confidence in ADR reporting was also associated with education level. Respondents with a higher education level were more likely to be confident to report ADRs compared to those with primary or no formal education (OR, 2.49; 95% CI, 0.77-8.1). Lack of awareness of the ADR monitoring system is still prevalent among Malaysian patients. The ease of completing the ADR form and education level are predictive of patient confidence to report ADRs. These factors should be considered in designing public promotional activities to encourage patient contributions to pharmacovigilance.
TL;DR: The leveled competencies, defined as the Fundamental, Skilled, and Advanced levels, and the included examples are expected to provide better-defined tools and resources to organizations that are creating educational and training programs, standardized role descriptions, or professional progression planning for clinical research professionals.
Abstract: Competency standards for clinical research professionals are being developed across the enterprise, based largely on the Core Competency Framework put forth by the Joint Task Force for Clinical Trial Competency (JTF). In late 2016, representatives from organizations around the world convened at a workshop hosted by the Multi-Regional Clinical Trial Center of Brigham and Women's Hospital and Harvard (MRCT Center) to discuss their use of the standards. A number of modifications were suggested that resulted in the publication of JTF Framework 2.0. Another suggested evolution of the Framework was to consider "leveling" the competencies, to reflect the increase in competency that occurs as individuals progress in their careers. This paper describes the process utilized and final outcome of this work. The leveled competencies, defined as the Fundamental, Skilled, and Advanced levels, and the included examples are expected to provide better-defined tools and resources to organizations that are creating educational and training programs, standardized role descriptions, or professional progression planning for clinical research professionals.
TL;DR: The results indicate that the start- up process is on average 5 to 6 months in total duration, and cycle times across all activities, including site identification, site selection, and study start-up, are faster for repeat sites than for new sites.
Abstract: Background:Site identification, site selection, and study start-up have become the focus of improvement by organizations conducting clinical trials.Methods:To examine and measure the process from site identification through site activation, Tufts Center for the Study of Drug Development (CSDD) conducted a comprehensive survey among pharmaceutical organizations, biotech companies, and contract research organizations (CROs). Responses from over 400 unique companies were gathered and analyzed.Results:The results indicate that the start-up process is on average 5 to 6 months in total duration, and cycle times across all activities, including site identification, site selection, and study start-up, are faster for repeat sites than for new sites. Comparisons between sponsor and CROs indicate that CROs completed all site-related activities 6 to 11 weeks faster than sponsors. Other areas impacting cycle times were examined, including centralized versus decentralized functions, investment in technology, and organi...
TL;DR: It is often difficult to find, interpret, and understand IRB policies on expanded access, and further research is needed to determine if and to what extent this negatively impacts patient access to investigational products outside of clinical trials.
Abstract: Background:The FDA allows patients with a serious or immediately life-threatening illness to use investigational medical products outside of clinical trials through its “expanded access” program. I...
TL;DR: The resulting “Safety Explorer” is a set of 6 interactive, web-based, open source tools designed to address the shortcomings of traditional, static reports for safety monitoring.
Abstract: Background
Frequent and thorough monitoring of patient safety is a requirement of clinical trials research. Safety data are traditionally reported in a tabular or listing format, which often translates into many pages of static displays. This poses the risk that clinically relevant signals will be obscured by the sheer volume of data reported. Interactive graphics enable the delivery of the vast scope of information found in traditional reports, but allow the user to interact with the charts in real time, focusing on signals of interest.
TL;DR: The availability and increasing use of innovative but more expensive targeted therapies were major drivers of increases in pharmaceutical expenditures for cancer treatment in Japan, and the effective use of genetic testing can mitigate these rising costs.
Abstract: Despite their benefits, the rapid development of new cancer treatments has been a significant driver of increasing health care expenditures in the face of limited health care budgets. In this study, we analyzed the prescribing trends for anticancer drugs from 2010 through 2016 in Japan and sought to identify unique trends that could provide a basis for future medical economic research aiming to develop more efficacious and cost-effective cancer therapies. We used publicly available marketing data for anticancer drugs in Japan for 2010-2016. The drugs selected for this research were categorized according to the Anatomical Therapeutic Chemical Classification System. We investigated the overall anticancer drug market size, the number of anticancer drugs, the top 30 selling anticancer categories, sales and prescription volumes, and changes in sales and prescription volumes between 2010 and 2016 in the country. The anticancer agent market expanded each year from 2010 to 2016, with sales exceeding 1 trillion yen in 2015. The proportion of molecular targeted drugs (antineoplastic mAbs and protein kinase inhibitors) among the top 30 selling anticancer categories has continued to increase, and both the sales and prescription volumes of these drugs exceeded those of drugs in other categories, suggesting that these treatments play a dominant role in cancer pharmacotherapy. The availability and increasing use of innovative but more expensive targeted therapies were major drivers of increases in pharmaceutical expenditures for cancer treatment in Japan. Therefore, the effective use of genetic testing can mitigate these rising costs.
TL;DR: The article is a summary of the poster of the same name presented at the DIA FDA Statistics Forum 2016, which took the third place in the poster award of the conference and suggests suggestions for improving the situation regarding statistical analysis, inference, and interpretation.
Abstract: Dissolution profile comparisons are used in the context of postapproval changes where the manufacturer has to demonstrate that the quality of the product is not affected by the change. Around this topic, basic statistical principles are in conflict with widely used interpretations of current guidelines, resulting in time-intensive discussions in pharmaceutical practice. From a statistician's perspective, the following suggestions could improve the situation regarding statistical analysis, inference, and interpretation: (1) A clear definition of the variability criterion for the similarity factor, such as that found in the EMA guideline, would be helpful. (2) Sample size recommendations should be interpreted as minimum, not as maximum, requirements. (3) In case of several batches per reference or test group, pooled comparisons should be performed instead of multiple batch-to-batch comparisons. (4) FDA Guideline recommendations concerning multivariate equivalence procedures for highly variable dissolution profiles are based on the state of statistical knowledge in 1997 and need to be updated. (5) The T2 test for equivalence is an appropriate method for comparing highly variable dissolution profiles. Application of the T2 test for equivalence enables reliable equivalence decisions and satisfies the intention of reaching scientific evidence in decision making. Software implementations of this test are available in R and SAS. The article is a summary of the poster of the same name presented at the DIA FDA Statistics Forum 2016. The poster took the third place in the poster award of the conference.