Showing papers by "Tufts Center for the Study of Drug Development published in 2011"

Pharmaceutical Innovation in the 21st Century: New Drug Approvals in the First Decade, 2000–2009

Abstract: The first decade of the 21st century was a challenging period for the pharma sector and could prove to be a turning point in the evolution of the industry. We examine drug development performance metrics for new product approvals during 2000-2009 and compare them with those of the prior two decades. The results indicate that, whereas total approvals are currently at a 25-year low, the percentage of priority products is nearly 50% of the total--a 30-year high. Following enactment of the Prescription Drug Use Fee Act of 1992 (PDUFA), the mean duration of the approval phases of drug development declined by more than 1 year over the 30-year period--to a low of 1.2 years in 2005-2009--whereas the duration of the clinical phases increased. The longer clinical phases were due, in part, to a greater number of approved central nervous system (CNS) and antineoplastic agents, two therapeutic classes with relatively long average development times (8.1 and 6.9 years, respectively). The results provide the underpinnings of a fundamental shift in the structure of the research-based industry.

Antibody-based therapeutics to watch in 2011.

Abstract: This overview of 25 monoclonal antibody (mAb) and 5 Fc fusion protein therapeutics provides brief descriptions of the candidates, recently published clinical study results and on-going Phase 3 studies. In alphanumeric order, the 2011 therapeutic antibodies to watch list comprises AIN-457, bapineuzumab, brentuximab vedotin, briakinumab, dalotuzumab, epratuzumab, farletuzumab, girentuximab (WX-G250), naptumomab estafenatox, necitumumab, obinutuzumab, otelixizumab, pagibaximab, pertuzumab, ramucirumab, REGN88, reslizumab, solanezumab, T1h , teplizumab, trastuzumab emtansine, tremelimumab, vedolizumab, zalutumumab and zanolimumab. In alphanumeric order, the 2011 Fc fusion protein therapeutics to watch list comprises aflibercept, AMG-386, atacicept, Factor VIII and Factor IX-Fc. Commercially-sponsored mAb and Fc fusion therapeutics that have progressed only as far as Phase 2/3 or 3 were included. Candidates undergoing regulatory review or products that have been approved may also be in Phase 3 studies, but these were excluded. Due to the large body of primary literature about the candidates, only selected references are given and results from recent publications and articles that were relevant to Phase 3 studies are emphasized. Current as of September 2010, the information presented here will serve as a baseline against which future progress in the development of antibody-based therapeutics can be measured.

Competitiveness in follow-on drug R&D: a race or imitation?

Abstract: The development of 'follow on' or 'me too' drugs - generally defined as a drug with a similar chemical structure or the same mechanism of action as a drug that is already marketed - has attracted contrasting views. Some have argued that follow-on drugs often provide useful alternative or enhanced therapeutic options for particular patients or patient subpopulations, as well as introducing price competition. Others, however, consider that the development of such drugs is duplicative and that the resources needed would be better directed elsewhere. Implicit in some of this criticism is the notion that the development of me-too drugs is undertaken after a first-in-class drug has made it to market and proved commercially successful. In this Perspective, using analysis of development and patent filing histories of entrants to new drug classes in the past five decades, we provide new evidence that the development of multiple new drugs in a given class is better characterized as a race, rather than the imitation of successful products.

A dearth of new meds.

Abstract: The authors looks at a study by the Tufts Center for the Study of Drug Development, which found that pharmaceutical companies are no longer producing new central nervous system medicines to treat psychiatric and neurodegenerative disorders because of the high cost involved. Topics include the length of time it takes to develop neuropsychiatric drugs, what makes these drugs so risky, and information on the Coalition Against Major Diseases and the Cures Acceleration Network.

Variability in Protocol Design Complexity by Phase and Therapeutic Area

Abstract: The Tufts Center for the Study of Drug Development analyzed 8,317 clinical trial protocols to benchmark protocol complexity by phase and therapeutic area and to characterize trends in clinical trial complexity and the burden placed on study staff to execute protocol procedures between 2000 and 2007. Wide variability in protocol complexity and work burden was observed across therapeutic areas, within and between clinical research phases. Phase 1 protocols are the most complex and the most demanding to execute. The mean number of total procedures per protocol in phase 4 studies and the work burden associated with phase 1 protocols grew the fastest between the periods 2000-2003 and 2004–2007. The complexity and work burden of phase 3 protocols also grew rapidly during this period. Protocols in anti-infectives, immunomodulation, CNS, and oncology are consistently the most complex and burdensome to execute. Reasons for the wide variability in protocol complexity and work burden by phase and therapeutic area are discussed. This study provides insight into areas where protocol design improvements should be targeted.

FDA's risk evaluation and mitigation strategies (REMS): effective and efficient safety tools or process poltergeist?

Abstract: Implementation of REMS began in March 2008 and by mid-2011 close to 200 New Molecular Entities (NMEs) and New Drug Applications (NDAs) (i.e., NMEs plus new doses and formulations of drugs) approved by FDA were required to have a REMS. As the REMS program expands, there has been an increasing chorus of stakeholders who have expressed a range of concerns and criticisms about the program's impact on the health care system. Yet, these impacts still remain underexplored by academic study. The authors conducted a series of qualitative interviews with individuals representing the experiences and opinions of five stakeholder groups involved in various aspects of REMS programs. The groups were comprised of representatives of biopharmaceutical companies, payers, health care providers (HCPs), pharmacists, and patient advocacy organizations. Questions were organized around the following themes: REMS implementation and administration; REMS components (i.e., medication guides, communication plans, and elements to assure safe use); effects on patient access and delivery of care; program outcomes; and, issues specific to each stakeholder group. What was most surprising was not that respondent groups with such divergent perspectives and diverse roles within the REMS program disagreed on certain points, but rather that they agreed on so many points. There was general agreement that the program is burdensome and not an improvement over previous risk management programs. Respondents also concurred almost unanimously that the patient information is weighted much too heavily on the risk end of the risk/benefit scale. Similarly, there was general concern from all the responder groups about uncompensated time and resources expended by HCPs and pharmacists. While some positive aspects were noted, these tended to be viewed as opportunities for improvement rather than actual benefits of the REMS program as currently implemented. As PDUFA V draws ever nearer, it's clear that FDA is attempting to address the program's shortcomings but it is clear that more needs to be done.

Factors Influencing Investigative Site Willingness and Ability to Participate in Clinical Trials

Abstract: The sponsor-site relationship is an essential consideration in investigative sites’ willingness to participate in clinical trials and sites’ ability to perform successfully. To better understand factors that impact this relationship, the Tufts Center for the Study of Drug Development, in conjunction with a working group of 10 pharmaceutical and biotechnology companies, developed a comprehensive two-part survey to examine clinical trial performance and investigator decisions to participate in a clinical study. Our respondents, clinical investigators worldwide, also provided company-specific ratings on training, investigator payments, receipt of supplies, study protocols, patient recruitment, and overall communication. A total of 3,516 surveys were completed for this study. The results indicate that having study information at the outset, sufficient numbers of eligible participants, adequate payments, and recruitment support are the factors that most impact site performance and willingness to participate. According to respondents, communication is a key issue to improving site operating efficiency. The results reveal how sponsors can help sites with challenges to operating efficiency, including patient recruitment, technology, communication, and financial operations.

Biopharmaceutical industry perspectives on the business prospects for personalized medicine

Abstract: Aim: Personalized medicine is entering its second decade, yet the role it will play in addressing the biopharmaceutical industry’s productivity gap and the rising cost of healthcare is still a matter of speculation. So what does the biopharmaceutical industry itself say about the business prospects for personalized medicine? Materials & methods: The authors conducted interviews with 20 science and business experts from 13 companies to find out. In this article, particular attention is paid to drug–diagnostic codevelopment, so-called companion diagnostics. Results: The results of the interviews are discussed in light of perspectives from various stakeholders available from the literature in the public domain. In brief, biopharmaceutical acknowledges the many difficulties that plague this path to product development with particular concern for knowledge gaps in the scientific base, the timing of studies during development, as well as the regulatory, reimbursement and commercial hurdles that can thwart appro...

Are Pharmacists a Viable Channel for Education about Clinical Trial Participation

Abstract: Clinical research is fundamental to improving public health, yet public awareness of and engagement in clinical research is very low, as is public trust in the clinical research enterprise. Hypothesizing that pharmacists represent an untapped resource to educate and engage the public about clinical research, this study examines public perspectives on receiving clinical research information from pharmacists. In a 19-item survey, the majority (72%) of the 2,650 respondents were very or somewhat interested in receiving clinical trial information from a pharmacist; but <1% currently receive it and <2% ever asked. Primary interests include information about finding a trial, safety of trials, and ways to learn more; printed information provided at the pharmacy or by email are preferred methods of receiving information. Interest varies significantly among respondent groups, but excepting non-pharmacy users, all respondents desire information at rates greater than 65%, regardless of demographics, knowledge or experience of clinical trials, and patient-pharmacist relationships. These results suggest that pharmacy-directed outreach and recruitment strategies could see high rates of success.

A New Mechanism for Tracking Publicly Available Study Volunteer Demographics.

Abstract: The importance of gathering and monitoring aggregate demographic data on the annual population of study volunteers in FDA-regulated clinical trials is widely acknowledged. To date, no formal mechanism exists to capture this information. The Tufts Center for the Study of Drug Development identified and tested a publicly available source of information on clinical trial participant data, NDA Reviews stored in the FDA’s drugs@FDA database, to determine its accuracy, reliability, and feasibility. Thirty-seven new drug applications approved between 2006 and 2008 were evaluated and compared with published sources of demographic data. The authors conclude that the approach described here—NDA review extraction—provides reasonably reliable and conservative estimates of study volunteer demographics and can serve as a useful baseline until Clinicaltrials.gov or other, more complete, public sources become available.

Dearth of clinically useful diagnostics limits growth of personalized medicine

Abstract: Pharmacogenomics explores the ways in which genetic variations can be used to predict whether an individual patient will benefit from a drug, have a bad response or no response at all [1]. Knowledge of genetic variance can guide drug development or dosing tailored to an individual’s specific circumstances. This, in turn, may reduce the chance of adverse drug reactions, maximize the probability of better health outcomes and diminish costs [2,3].

Personalized medicine: are payers the weak link?

Abstract: there is no codevelopment of tests. Tests are developed post hoc as a way of personalizing a drug, such as in the examples of abacavir and warfarin [8]. Despite the success stories, pharmaco genomics has had limited impact on clinical practice to date. The list of FDA/EMA-approved companion diagnostics is still relatively short, perhaps a dozen or so. There are significant clinical, financial and ethical barriers to the successful implementation of pharmacogenomics. Scientifically, the process of biomarker discovery and validation has been disappointingly slow. Additionally, regulatory and reimbursement issues have been problematic, particularly with respect to companion diagnostics, but also drugs that lack clinically effective diagnostics. To illustrate this point, gefitinib only works in approximately 10% of patients with advanced non-small-cell lung cancer. In June 2009, the FDA partially withdrew the drug, no longer allowing its prescription to new non-small-cell lung cancer patients, as no useful EGF receptor (EGFR) biomarker test is (yet) commercialized in the USA to pinpoint positive responders. As a result, gefitinib has encountered considerable market access issues, as payers are quite reluctant to reimburse. Even with FDA/EMA-approved biomarker tests lingering questions persist regarding their clinical effectiveness. A case in point is warfarin, which illustrates the acute translational gap that exists between knowledge and application. Tests suggest patients deficient in a certain enzyme activity (CYP2C9) may require a lower warfarin dose or more frequent monitoring and may be at risk of bleeding episodes. Since 2007, the FDA has been recommending genotyping for all patients being prescribed warfarin. In spite of this, in April 2009, the Centers for Medicare and Medicaid Services (CMS) decided not to routinely pay for genetic tests intended to help doctors determine Pharmacogenomics explores the ways in which genetic variations can be used to predict whether an individual patient will benefit from a drug, have a bad response or no response at all. Accordingly, therapies may be tailored to certain genetic characteristics of individual patients or subpopulations, drawing on data gathered from a variety of sources, including tests for biomarkers [1]. Knowledge of genetic variance can guide the selection of appropriate drugs or dosing tailored to an individual’s specific circumstances. This, in turn, may reduce the chance of adverse events, maximize the probability of better health outcomes and diminish costs [2,3]. In some instances, tests select which patients should or should not take a particular medication. For example, a test is used in conjunction with the breast cancer biologic trastuzumab to detect patients whose tumors overexpress HER2 protein [4,5]. In other cases, tests are used to predict the probability of adverse events associated with the use of a particular drug [6]. For example, there is a test which links hypersensitivity reactions to the HIV/AIDS drug abacavir to a specific genotype. Furthermore, there are tests which suggest ways to modify dosing in patients with an innately poor ability to metabolize a certain drug. In the case of warfarin, for instance, tests detect variations in the way individuals metabolize the blood-thinning agent. This may help to optimize dosing. Some personalized medicines are developed pharmacogenomically, concurrently with companion diagnostics. Trastuzumab was codeveloped with a pharmacogenomics test, which was US FDA/EMA approved and recommended prior to prescribing. There are also instances, such as the cancer biologic cetuximab, when a drug was codeveloped with a test but testing is not recommended by any regulatory authority prior to prescribing [7]. However, in most cases, at present “...in order to achieve widespread favorable reimbursement and clinical uptake for genetic tests and targeted therapies, manufacturers will need to bring more, and better, clinical evidence to the market place...”