A Study on the Application and Use of Artificial Intelligence to Support Drug Development.

Purpose: The Tufts Center for the Study of Drug Development (CSDD) and the Drug Information Association (DIA) in collaboration with 8 pharmaceutical and biotechnology companies conducted a study examining the adoption and effect of artificial intelligence (AI), such as machine learning, on drug development. The study was conducted to clarify and understand AI adoption across the industry and to gather detailed insights into the spectrum of activities included in the definition of AI. The study investigated and identified analytical platforms and innovations across pharmaceutical and biotechnology companies currently being used or planned for in the future.

Cost-effectiveness analysis of three algorithms for diagnosing primary ciliary dyskinesia: a simulation study.

Background: Primary Ciliary Dyskinesia (PCD) diagnosis relies on a combination of tests which may include (a) nasal Nitric Oxide (nNO), (b) High Speed Video Microscopy (HSVM) and (c) Transmission Electron Microscopy (TEM). There is variability in the availability of these tests and lack of universal agreement whether diagnostic tests should be performed in sequence or in parallel. We assessed three combinations of tests for PCD diagnosis and estimated net sensitivity and specificity as well as cost-effectiveness (CE) and incremental cost-effectiveness (ICE) ratios.

Impact of Regulatory Incentive Programs on the Future of Pediatric Drug Development.

Surveys evaluating industry experience with performing pediatric studies under the Best Pharmaceutical for Children Act (BPCA) and Pediatric Research Equity Act (PREA) regulatory regime were conducted by Tufts Center for the Study of Drug Development (Tufts CSDD) in 2000, 2006, and 2016. These survey results are being used to assess the future impact of regulatory incentive programs on generating pediatric specific labeling information and development of age-appropriate drug formulations. A second perspective will be provided through the experience and expertise of neonatal/pediatric clinicians and researchers with a focus on the urgent need for the study of new and existing drugs in this vulnerable population (especially with 90% of drugs in neonates still being used off-label).

Are Regulation and Innovation Priorities Serving Public Health Needs?

A host of challenges confront healthcare authorities worldwide. Topping the list is the demand for innovative new medicines to treat a range of both infectious and non-communicable diseases, while containing spiraling healthcare costs. The challenge is particularly great in therapeutic areas where, despite significant medical need and economic impact, the technical challenges and commercial risk of development serve as disincentives to drug sponsors.

Global Public Attitudes About Clinical Research and Patient Experiences With Clinical Trials.

Importance: Effective, continuous improvement in patient engagement depends on an intimate understanding of public and patient perceptions and experiences in clinical research.

Objectives: To identify the views of clinical trial participants and nonparticipants and characterize trends in these views over time.

Design, Setting, And Participants: In this survey study, a questionnaire was administered online from May 8 to July 24, 2017, by the Center for Information and Study on Clinical Research Participation (CISCRP), and findings were compared with previous studies conducted in 2013 and 2015.

Efficacy and Effectiveness Too Trials: Clinical Trial Designs to Generate Evidence on Efficacy and on Effectiveness in Wide Practice.

Efficacy trials, designed to gain regulatory marketing approval, evaluate drugs in optimally selected patients under advantageous conditions for relatively short time periods. Effectiveness trials, designed to evaluate use in usual practice, assess treatments among more typical patients in real-world conditions with longer follow-up periods. In "efficacy-to-effectiveness (E2E) trials," if the initial efficacy trial component is positive, the trial seamlessly transitions to an effectiveness trial component to efficiently yield both types of evidence.

Analysis of Review Times for Recent 505(b)(2) Applications.

Background: Annual review statistics released by the Food and Drug Administration (FDA) and a number of studies indicate that the review process improvements introduced under various versions of the Prescription Drug Use Fee Act (PDUFA) have been successful in decreasing average times for marketing approval of new molecular entities (NMEs). Similar statistics are not available, however, for non-NME new drug applications. These application types, such as those covered under section 505(b)(2) of the Food and Drug and Cosmetic Act, represent more than half of all new drug application (NDA) submissions annually and they are primarily based on previously approved drugs.

Estimated lifetime survival benefit of tumor treating fields and temozolomide for newly diagnosed glioblastoma patients.

Aim: To estimate the mean lifetime survival benefit, an essential component of health economic evaluations in oncology, of adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) for newly diagnosed glioblastoma patients.

Methods: We integrated EF-14 trial data with glioblastoma epidemiology data. The model provided for an evidence-based approach to estimate lifetime survival for the material number of EF-14 trial patients still alive at 5 years.

Evaluating the Completeness of ClinicalTrials.gov.

Background: To date, although studies have been conducted to assess compliance with listing clinical trial information, to our knowledge there is nothing in the literature examining the completion and accuracy of clinical trial site information on ClinicalTrials.gov .

Methods: We compared clinical trial information originating from ClinicalTrials.

Can Regenerative Medicine Help Close the Gap Between the Medicine Pipeline and Public Health Burden of Cardiovascular and Musculoskeletal Diseases?

Purpose: This commentary discusses the therapeutic and economic potentials of regenerative medicine (RM) by addressing how the reprioritization of resources in drug development may alleviate unmet medical need across many diseases, but especially cardiovascular diseases (CVDs) and musculoskeletal diseases (MSDs), the leading causes of mortality and morbidity, respectively, in the United States.

Methods: Data and perspectives represented in this commentary were obtained through an online literature search, public press releases from federal agencies and companies, online opinion pieces, published journal articles, and consulting agency reports; however, there were limitations to the available data because of the breadth and novelty of the therapeutic modalities involved.

Findings: Currently, the misallocation of resources within the therapeutic areas of CVDs and MSDs are possibly contributing to low approval rates, high cost of drug treatments, and consequently, disease burden.

Assessing the Financial Benefits of Faster Development Times: The Case of Single-source Versus Multi-vendor Outsourced Biopharmaceutical Manufacturing.

Purpose: The extent to which new drug developers can benefit financially from shorter development times has implications for development efficiency and innovation incentives. We provided a real-world example of such gains by using recent estimates of drug development costs and returns.

Methods: Time and fee data were obtained on 5 single-source manufacturing projects.

New Benchmarks Characterizing Growth in Protocol Design Complexity.

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 < .

Baseline Assessment of the Evolving 2017 eClinical Landscape.

The volume and diversity of data collected to support each clinical study has increased dramatically in response to the rising scope and complexity of global drug development programs. The Tufts Center for the Study of Drug Development conducted an online survey of 257 unique global companies-77% drug development sponsors and 23% contract service providers-to assess clinical data management practices and experiences. Study results indicate that companies are using an average of 6 different applications to support each clinical study and that companies are collecting a range of data types including that from case report forms, lab procedures, pharmacokinetics, biomarker, outcomes assessment, mobile health, and social media.

The Use of Real-World Evidence and Data in Clinical Research and Postapproval Safety Studies.

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.

Assessing Study Start-up Practices, Performance, and Perceptions Among Sponsors and Contract Research Organizations.

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.

Assessing the Financial Value of Patient Engagement: A Quantitative Approach from CTTI's Patient Groups and Clinical Trials Project.

Background: 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.

Methods: 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.

Challenges Involved in the Development and Delivery of Abuse-deterrent Formulations of Opioid Analgesics.

Purpose: This commentary examines the development, regulatory, and reimbursement challenges facing abuse-deterrent formulation (ADF) products.

Methods: In January 2017, the Tufts Center for the Study of Drug Development convened a roundtable to explore clinical development, regulatory, and reimbursement challenges with respect to ADFs of opioid analgesics. Roundtable participants, who included a range of pharmaceutical industry and other experts, discussed multiple challenges.

Rising Drug Costs Drives the Growth of Pharmacy Benefit Managers Exclusion Lists: Are Exclusion Decisions Value-Based?

Objective: We examine whether drugs' excluded versus recommended status on pharmacy benefit manager exclusion lists corresponds to evidence from cost-effectiveness analyses, lack of evidence, or rebates.

Data Sources: To find cost-effectiveness data for drugs on 2016 exclusion lists of CVS Caremark and Express Scripts, we searched the Tufts Cost-Effectiveness Analysis Registry and the peer-reviewed literature.

Study Design: For each excluded and recommended drug, we compared the mean cost-per-QALY, and we calculated the difference between the numbers of excluded and recommended drugs for which we could find no cost-effectiveness evidence.

Mapping the Landscape of Patient-centric Activities Within Clinical Research.

Purpose: Although there has been more involvement by patients in the drug-development process, there are not a lot of published data that quantify patient-centric activities or that document these activities across a large scale. In order to examine the patient-centricity landscape and to quantify the adoption and implementation of these initiatives, the Tufts Center for the Study of Drug Development and the Drug Information Association collaborated on a research study. The study examined patient-centric activities implemented by pharmaceutical, biotechnology, and contract research organizations, as well as activities being piloted or in the planning stages.

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial.

Background: Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients.