Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act . The FDA's "breakthrough therapy" designation is not intended to imply that a drug is actually a "breakthrough" or that there is high-quality evidence of treatment efficacy for a particular condition; rather, it allows the FDA to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases. The FDA has other mechanisms for expediting the review and approval process for promising drugs, including fast track designation, accelerated approval , and priority review .
34-497: A breakthrough therapy designation can be assigned to a drug if "it is a drug which is intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition" and if the preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." Requests are reviewed by
68-627: A breakthrough designation for a drug candidate with a marketing advantage that may be undeserved. The FDA acknowledges that the name "breakthrough therapy" may be misleading. It was never meant to imply that these drugs are actually "breakthroughs," and it does not ensure that they will provide clinical benefit, but still critics complain that they are based on preliminary evidence, including changes in surrogate markers such as laboratory measurements, that often don't reflect "meaningful clinical benefit." The FDA guidance states: "Not all products designated as breakthrough therapies ultimately will be shown to have
102-481: A couple of hundred thousand dollars remained unspent. After Epstein's 2008 conviction, Harvard president Drew Faust decided that the university would no longer accept his donations. A report commissioned by the university found that Nowak allowed Epstein to visit the PED offices more than 40 times after his conviction, to maintain an office with a phone line and webpage, and to interact with students at PED. In 2020,
136-612: A large sum of money to support Nowak's work and set up a center for studying cooperation in evolution. Nowak was the director of Harvard's resulting Program for Evolutionary Dynamics (PED) from 2003 until 2020, when he was disciplined by being suspended from supervising undergraduate research for two years and having his institute permanently closed down as a punishment for having provided an office, keycard, and passcode, and for allowing Epstein free and unlimited access to PED for over ten years after his conviction for sex crimes. Martin Nowak
170-739: A mathematical model which explained the puzzling delay between HIV infection and AIDS in terms of the evolution of different strains of the virus during individual infections, to the point where the genetic diversity of the virus reaches a threshold whereby the immune system can no longer control it. This detailed quantitative approach depended on assumptions about the biology of HIV which were subsequently confirmed by experiment. At Harvard, Nowak continued his work on virus dynamics, cancer dynamics, and evolutionary game theory. In 2004, he established evolutionary game dynamics in finite populations. In 2005 and 2006 he wrote key papers establishing evolutionary graph theory. In 2006, he suggested that cooperation
204-444: A two year ban on Nowak supervising undergraduate research, serving as the principal investigator of new grants, and supervising new graduate students or postdoctoral fellows. Nowak said he would "take the lessons from this time with me as I move forward". The sanctions against Nowak were lifted in 2023. Nowak has authored books and scientific papers on topics in evolutionary game theory , cancer , viruses , infectious disease ,
238-558: Is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a single disease , and often all the therapies are pharmaceutical (although it can also involve non-medical therapy, such as the combination of medications and talk therapy to treat depression). 'Pharmaceutical' combination therapy may be achieved by prescribing/administering separate drugs, or, where available, dosage forms that contain more than one active ingredient (such as fixed-dose combinations). Polypharmacy
272-511: Is a related term, referring to the use of multiple medications (without regard to whether they are for the same or separate conditions/diseases). Sometimes "polymedicine" is used to refer to pharmaceutical combination therapy. Most of these kinds of terms lack a universally consistent definition, so caution and clarification are often advisable. Conditions treated with combination therapy include tuberculosis , leprosy , cancer , malaria , and HIV / AIDS . One major benefit of combination therapies
306-506: Is an Austrian -born professor of mathematics and biology at Harvard University . He is one of the leading researchers in evolutionary dynamics . Nowak has made contributions to the fields of evolutionary theory , cooperation , viral dynamics , and cancer dynamics. Nowak held professorships at Oxford University and at the Institute for Advanced Study , Princeton, before being recruited by Harvard in 2003 when Jeffrey Epstein donated
340-458: Is constructive because of cooperation, and that we might add “natural cooperation” as a third fundamental principle of evolution beside mutation and natural selection. In a paper featured on the front cover of Nature in 2007, Nowak and colleagues demonstrated that the transition of irregular verbs to regular verbs in English over time obeys a simple inverse-square law , thus providing one of
374-711: Is famous for his extensive contributions to various scientific disciplines, including evolutionary game theory, virology, cancer dynamics, and the evolution of cooperation. Throughout his career, Nowak has collaborated with notable figures such as Robert May , Karl Sigmund , and John Maynard Smith . His work spans a wide range of topics, from the somatic evolution of cancer to the origins of language and prelife. Nowak has authored over 300 scientific publications, including many contributions to Nature and Science . Aside from his scientific career, Nowak has also authored five books. His 2006 work Evolutionary Dynamics received praise for its unique perspective on theoretical biology and won
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#1732776138140408-592: Is that they reduce development of drug resistance since a pathogen or tumor is less likely to have resistance to multiple drugs simultaneously. Artemisinin -based monotherapies for malaria are explicitly discouraged to avoid the problem of developing resistance to the newer treatment. Combination therapy may seem costlier than monotherapy in the short term, but when it is used appropriately, it causes significant savings: lower treatment failure rate, lower case-fatality ratios, fewer side-effects than monotherapy, slower development of resistance, and thus less money needed for
442-559: The Financial Times . With Sarah Coakley, Nowak edited the 2013 book Evolution, Games, and God: The Principle of Cooperation , published by Harvard University Press . The volume features articles from experts in multiple fields who explore the interplay between theology and evolutionary theory as pertaining to cooperation and altruism . Nowak is a corresponding member of the Austrian Academy of Sciences . He won
476-817: The Albert Wander Prize , the Akira Okubo Prize , the David Starr Jordan Prize and the Henry Dale Prize . Nowak identifies as a Roman Catholic , advocating for the compatibility of science and religion in the pursuit of truth. His 2024 book, Beyond, is a poetic exploration of the connection between religion and science. In 2015, he received the honorary degree Doctor of Humane Letters from the Dominican School of Philosophy & Theology at Berkeley . Nowak
510-514: The Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). CDER receives approximately 100 requests per year for breakthrough designation. Historically, about one third were approved. CBER receives 15–30 requests per year. Sponsors must apply for breakthrough status separately for each indication they intend to label the drug for. Breakthrough designation applications are submitted as an amendment to
544-471: The IND applications, usually prior to end of Phase II meeting. Drugs that have been granted breakthrough status are given priority review. The FDA works with the sponsor of the drug application to expedite the approval process. This expedited process can include rolling reviews, smaller clinical trials, and alternative trial designs. Critics have said that the name is misleading and provides companies that obtain
578-491: The R.R. Hawkins Award . In 2011, he co-authored SuperCooperators, which argues for cooperation as a fundamental principle of evolution, garnering positive reviews. Additionally, Nowak has edited books, including Evolution, Games, and God, which examines the relationship between theology and evolutionary theory. He has received numerous awards for his contributions to science, including the Weldon Memorial Prize ,
612-720: The Templeton Foundation , where he was also a member of their Board of Advisers. He was appointed Director of the Program for Evolutionary Dynamics (PED). The PED was funded with a large sum of money from the Jeffrey Epstein VI Foundation . In 2003, Epstein had introduced himself as a science philanthropist cementing the initial interaction with a large donation to Harvard. Scientific American reported that Nowak's team received US$ 6.5 million initially, with nothing released to him after 2007,
646-687: The Weldon Memorial Prize , the Albert Wander Prize, the Akira Okubo Prize, the David Starr Jordan Prize and the Henry Dale Prize. Nowak is a Roman Catholic . In a 2007 lecture at Harvard, he argued that science and religion occupied different but complementary roles in humans' search for meaning, stating: "Science and religion are two essential components in the search for truth. Denying either
680-652: The evolution of language , and the evolution of cooperation . At Oxford, he helped to establish the fields of virus dynamics and spatial games (which later became evolutionary graph theory). He continued his collaboration with Karl Sigmund in game theory, proposing generous tit-for-tat and win-stay, lose-shift, inventing adaptive dynamics, alternating games and indirect reciprocity. He collaborated with John Maynard Smith on genetic redundancy, with Baruch Blumberg on hepatitis B virus, with George Shaw and Andrew McMichael on HIV. He worked with Robert May on evolution of virulence. In 1990, Nowak and Robert May proposed
714-843: The Equations of Life discusses the evolution of various biological processes. Reviewing Evolutionary Dynamics in Nature , Sean Nee called it a "unique book" that "should be on the shelf of anyone who has, or thinks they might have, an interest in theoretical biology." The book received the Association of American Publishers ' R.R. Hawkins Award for the Outstanding Professional, Reference or Scholarly Work of 2006. Nowak's book SuperCooperators: The Mathematics of Evolution, Altruism and Human Behaviour (Or, Why We Need Each Other to Succeed) , co-authored with Roger Highfield ,
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#1732776138140748-744: The Institute of Mathematics at the University of Vienna. In 2001, he was elected into the Austrian Academy of Sciences. From 1989 to 1998, Nowak worked at the University of Oxford with Robert May . First, he was an Erwin Schrödinger postdoctoral Scholar, then a Junior Research Fellow at Wolfson College, then a Junior Research Fellow at Keble College. From 1992, he was a Wellcome Trust Senior Research Fellow. From 1997 to 1998, Nowak
782-560: The development of new drugs. Combination therapy has gained momentum in oncology in recent years, with various studies demonstrating higher response rates with combinations of drugs compared to monotherapies, and the FDA recently approving therapeutic combination regimens that demonstrated superior safety and efficacy to monotherapies. In a recent study about solid cancers, Martin Nowak , Bert Vogelstein , and colleagues showed that in most clinical cases, combination therapies are needed to avoid
816-558: The evolution of resistance to targeted drugs. Furthermore, they find that the simultaneous administration of multiple targeted drugs minimizes the chance of relapse when no single mutation confers cross-resistance to both drugs. Various systems biology methods must be used to discover combination therapies to overcome drug resistance in select cancer types. Recent precision medicine approaches have focused on targeting multiple biomarkers found in individual tumors by using combinations of drugs. However, with 300 FDA-approved cancer drugs on
850-585: The findings of the paper are conclusive and that the field of social evolution should move beyond inclusive fitness theory. He has over 300 scientific publications, of which 40 are in Nature and 15 in Science . Nowak's research interests include: Nowak's first book Virus Dynamics: Mathematical Principles of Immunology and Virology , written with Robert May, was published by Oxford University Press in 2001. Nowak's 2006 book Evolutionary Dynamics: Exploring
884-425: The first quantitative laws in the evolution of language. In 2010 a paper by Nowak, E. O. Wilson , and Corina Tarnita, in Nature , argued that standard natural selection theory represents a simpler and superior approach to kin selection theory in the evolution of eusociality . This work has led to many comments including strong criticism from proponents of inclusive fitness theory. Nowak maintains that
918-512: The market, there almost 45,000 possible two-drug combinations and almost 4.5 million three-drug combinations for to choose from. That level of complexity is one of the primary impediments to the growth of combination therapy in oncology. The National Cancer Institute has recently highlighted combination therapy as a top research priority in oncology. Combination therapy with two or more antibiotics are often used in an effort to treat multi-drug resistant Gram-negative bacteria. Monotherapy, or
952-455: The substantial improvement over available therapies suggested by the preliminary clinical evidence at the time of designation. If the designation is no longer supported by subsequent data, FDA may rescind the designation." As of August 2020, the FDA had granted breakthrough device designations to 298 medical devices in total since its inception, including 50 for the year 2020. Combination therapy Combination therapy or polytherapy
986-400: The university placed Nowak on paid academic leave for violation of campus policies including professional conduct and campus access. In 2021, Harvard decided a proportionate response to the severity of Nowak's failure to follow Harvard policies was to close the institute founded with Epstein's money, to donate the money remaining to a foundation helping victims of sexual assaults, and to impose
1020-514: The use of a single therapy, can be applied to any therapeutic approach, but it is most commonly used to describe the use of a single medication . Normally, monotherapy is selected because a single medication is adequate to treat the medical condition. However, monotherapies may also be used because of unwanted side effects or dangerous drug interactions . Martin Nowak Martin Andreas Nowak (born April 7, 1965 )
1054-645: Was a professor of mathematical biology. In 1998, Martin Nowak was recruited by the Institute for Advanced Study in Princeton. He was Head of the Institute's first Initiative in Theoretical Biology from 1998 until 2003. In 2003, Nowak was recruited to Harvard University as Professor of Mathematics and Biology. Nowak was also co-director with Sarah Coakley of the Evolution and Theology of Cooperation project at Harvard University , sponsored by
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1088-600: Was a third fundamental principle of evolution beside mutation and selection. In 2007, he proposed prelife - a theory for the origin of life. In 2008 and 2009 he suggested that positive interaction, but not punishment, promotes evolution of cooperation. In a paper in Science in 2006, Nowak enunciated and unified the mathematical rules for the five understood bases of the evolution of cooperation ( kin selection , direct reciprocity , indirect reciprocity , network reciprocity , and group selection ). Nowak suggests that evolution
1122-473: Was born in Vienna, Austria. He studied at Albertus Magnus Gymnasium and the University of Vienna , earning a doctorate in biochemistry and mathematics in 1989. He worked with Peter Schuster on quasi-species theory and with Karl Sigmund on evolution of cooperation. Nowak received the highest Austrian honors ( Sub auspiciis Praesidentis ) when awarded his degree. In 1993, he received his "Habilitation" at
1156-511: Was published in 2011. SuperCooperators is both an autobiography of Nowak and a popular presentation of his work in mathematical biology on the evolution of cooperation, the origin of life, and the evolution of language. In the book, Nowak argues that cooperation is the third fundamental principle of evolution, next to mutation and natural selection . SuperCooperators received positive reviews in The New York Times , Nature , and
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