Accelerated Pathways for Authorisation of Drugs

Accelerated Pathways for Authorisation of Drugs Mary Treasa Lohan Abstract and Summary Every year, thousands of chemical and biological entities are developed in the hope of making it to the shelf. The drug development process is the progression by which drugs will either be approved or not approved for use, and spans from discovery and preclinical testing to Phase IV of Clinical Trials (post marketing surveillance). The underpinning aim is to ensure the safety and efficacy of a drug before it can be approved for use. Given that only one in every 5,000 to 10,000 compounds that enter preclinical testing are approved for marketing, and that an average of 15 years is required to take a drug through the complete process, the drug development process is a long and costly one. The two main regulatory bodies in the world are the FDA (USA) and the EMA (EU) and while the drug approval process varies from the EU to the USA, the basic regulation process remains the same. Figure 1 Basic drug development regulation       (Kashyap et al., 2013) 1.1. Drug approval process in the US In brief, the process of drug approval in the US first involves the submission of an Investigational New Drug application by the Sponsor. This allows the Clinical Trials to commence once the data from the Preclinical trials shows that the drug is safe. Once the drug is shown to be safe and effective (Clinical Trials data), a New Drug Application is filed which is essentially an application to manufacture and sell the drug (Rick, 2009). 1.1. Drug approval process in the EU The application process for the EU, similar to the US, requires two steps. The first step is a clinical trial application to an individual member state, and then a marketing approval. The marketing approval in the EU can take one of three approaches The centralised procedure The mutual recognition procedure The decentralised procedure As mentioned before, the purpose of the drug development process is to ensure safe and effective drugs are available to the patient. However, both the US and EU processes are very lengthy procedures and often do not provide rapid patient access to drugs. There is of course a balance to be struck between providing patients with rapid access to medicines and ensuring adequate information is available regarding the risk-benefit factors of the drug, sometimes termed the evidence versus access challenge (Eichler et al., 2015). 1.2. Improvements In recent times however, much has been done to try and improve the situation (Baird et al., 2014). In the EU, there are two means to fast track approval of a drug; Accelerated assessment and Conditional marketing authorisation. The Conditional marketing authorisation process allows the approval of a medicine that address unmet medical needs of patients on the basis of less comprehensive data than normally required. The available data must indicate that the medicines benefits outweigh its risks and the applicant should be in a position to provide the comprehensive clinical data in the future (EMA, 2015). In 2014, the EMA initiated a pilot project for a new model of drug testing and marketing called Adaptive Pathways (also known as Adaptive Licensing, or more recently the terms Medicines Adaptive Pathways (MAPs) or Medicines Adaptive Pathways to Patients (MAPPs) have been used). This concept allows new drugs that would treat unmet medical needs to be launched on the market faster, based on an incomplete data set (Davis et al., 2016). This project aims to discuss Adaptive Pathways in general, the different types of Adaptive Pathways, as well as the types of drugs that are suitable for these pathways. Finally, the Adaptive Pathway approval strategies in the EU and the US will be discussed. 2.1. Adaptive Pathways 2014 saw the introduction of a pilot program by which drugs could potential to make it to the market faster in order to fulfil unmet medical needs, the Adaptive Pathway. The idea was to ensure timely patient access to new drugs, while ensuring adequate risk benefit information was available. The Adaptive Pathways model presented by the EMA is not a new route of marketing authorisation but rather makes use of existing regulatory approaches such as the conditional marketing authorisation or the standard marketing authorisation. Using this pilot program, drugs could be authorized conditionally or in a staggered fashion using data gathered throughout the life of the product. The three key principles of Adaptive Pathways are; Iterative development Gathering real-life evidence Early involvement of stakeholders Bearing in mind that drugs are approved through adaptive pathways based on incomplete data and are given market approval earlier in the development process, iterative development refers to the gathering of data to increase knowledge after authorisation. It is a staggered approach to widen the target population or expand the indication. The data collected can also be used to reduce any uncertainties that were present at the early approval stage. A key component of Adaptive Pathways is a well-defined prospective plan for collecting real-life data that can be used in conjunction with the Clinical Trials data to enhance the risk benefit ratio (Eichler et al., 2012). Communication between stakeholders is critical and helps to decide what medicines are suitable, and are also responsible for creating an agreed prospective plan required for data gathering throughout the lifecycle of the product. Stakeholders are involved from a very early stage and can include health technology assessment (HTA) bodies, patients, as well as regulators and healthcare professionals. 2.2. Benefits and challenges of Adaptive Pathways The obvious advantage of the Adaptive Pathway is that the patient can potentially have access to a drug in a much shorter time period than if the drug had to go through the standard application process. If the drug shows a good risk benefit outcome, the drug can be approved at an earlier stage, while real-life data is gathered at predefined intervals from patients to confirm effectiveness. There is also the opportunity for drugs to be fully approved within a shorter timeframe than normal.   Eichler also suggests that this process may reduce the overall cost of development by allowing better-informed decisions on product viability to be made earlier in the development process (Eichler et al., 2012). Eichler has published an article detailing the enablers of this new concept (Eichler et al., 2015). However, since the publication of the EMAs final report in July following the completion of the pilot program, a number of articles have been published which criticise the new concept (Eichler et al., 2012) (Woodcock, 2012). Unlike the standard authorisation, the Adaptive Pathway uses preliminary data and omits a number of steps that were designed to protect patients from unsafe and ineffective drugs and, this raises concerns as to whether this can potentially lead to increased risk to the patient. For adaptive Pathways to work, it is critical that evidence obtained after initial approval be taken into consideration. However, it has been found that healthcare professionals are often slow to abandon unsafe methods (Tatsioni et al., 2007). This is worrying as the basis of Adaptive Pathways is that reliable data is generated after authorisation that will shed more light on the risk benefit to the patient. Another serious concern relates to the life cycle management of the new drug (Davis et al., 2016). As mentioned earlier, a key principle of the Adaptive Pathway is gathering real-life evidence in post-marketing studies that would be used to update the risk benefit information. However, it would seem that in the case of conditionally approved drugs, the regulatory bodies have failed to ensure post-marketing study commitments are followed through (Banzi et al., 2015). It has also been suggested that where undesirable findings are encountered, companies may dispute these as unreliable results (McCabe et al., 2010) or may discount them because there are large financial gains or reputations at risk (Prasad et al., 2012). Moreover, the willingness of stakeholders to participate in a program that involves more uncertainty, and correspondingly perhaps more risk, than before will be one of the greatest challenges to the Adaptive Pathway. 2.3. Suitable drugs for Adaptive Pathways The report issued by the EMA suggests that drugs that treat infectious diseases, Alzheimers disease, degenerative diseases and rare cancers are potential candidates for this process with the objective of furthering their development and that suitable for the Adaptive Pathways would be those that treat rare diseases, where clinical data is not that common. The EMA have provided a flowchart to help companies determine if a product is an appropriate candidate or not, (Figure 2). Based on this, the key features of a drug that could be deemed suitable for this Adaptive Pathways approach are; iterative development, collaboration with HTA, and the use of real time data for regulatory purposes. Figure 2 Adaptive Pathway product eligibility flowchart While there is no strict restriction on what type of drugs are eligible for the Adaptive Pathways, the EMA states that this route is not to be applicable to all medicines, but only to medicines that are likely to address an unmet medical need(EMA, 2016). During the pilot, 62 applications were received from a variety of therapeutic areas with cancer therapies accounting for a large proportion (33%). It is worth noting that Orphan designated drugs are suitable candidates, with 5 making it through to Stage 1 Meetings (15 drugs had been given Orphan drug designation by the European Commission at the time of submission) (EMA, 2016). (EMA, 2016) 2.5. Adaptive Pathway approval strategy in the USA Within the USA, there are four approaches to getting drugs on the market as rapidly as possible, and in each case the drug must be intended to treat a serious condition. A serious condition is defined as a disease or condition associated with morbidity that has a substantial impact on day-to-day functioning Fast Track Breakthrough Therapy Accelerated Approval Priority Review Fast Track refers to the process, approved in 1992 under the Prescription Drug User Fee Act, by which drugs needed to treat serious conditions or to fulfil unmet medical needs are rapidly approved. According to the FDA, filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy (FDA, 2014). This strategy means more communication with the FDA regarding the drug development plan, data collection and clinical trials design. In addition, a Fast Track designated drug is potentially eligible for Accelerated Approval and Priority Review if it meets the applicable criteria. Breakthrough Therapy designation accelerates the development of drugs needed to treat serious conditions that have shown substantial advantages over existing treatments in early clinical studies (Poirier and Murphy, 2016). This strategy utilises a surrogate endpoint. A surrogate endpoint is a marker used to determine effectiveness of a drug, such as the shrinking of a tumour and is often used rather than actual clinical endpoints, such as survival rates. Another example would be a significantly improved safety profile compared to available therapy (FDA). In addition to the Fast Track designation benefits, Breakthrough Therapy drugs receive a vast amount of guidance with the drug development program. References   BAIRD, L. G., BANKEN, R., EICHLER, H. G., KRISTENSEN, F. B., LEE, D. K., LIM, J. C. W., LIM, R., LONGSON, C., PEZALLA, E. SALMONSON, T. 2014. Accelerated access to innovative medicines for patients in need. Clinical Pharmacology Therapeutics, 96, 559-571. BANZI, R., GERARDI, C. GARATTINI, S. 2015. Approvals of drugs with uncertain benefit-risk profiles in Europe. European journal of internal medicine, 26, 572-584. DAVIS, C., LEXCHIN, J., JEFFERSON, T., GØTZSCHE, P. MCKEE, M. 2016. Adaptive pathways to drug authorisation: adapting to industry? BMJ: British Medical Journal, 354. EICHLER, H. G., BAIRD, L. G., BARKER, R., BLOECHLà ¢Ã¢â€š ¬Ã‚ DAUM, B., BØRLUMà ¢Ã¢â€š ¬Ã‚ KRISTENSEN, F., BROWN, J., CHUA, R., DEL SIGNORE, S., DUGAN, U. FERGUSON, J. 2015. From adaptive licensing to adaptive pathways: Delivering a flexible lifeà ¢Ã¢â€š ¬Ã‚ span approach to bring new drugs to patients. Clinical Pharmacology Therapeutics, 97, 234-246. EICHLER, H. G., OYE, K., BAIRD, L. G., ABADIE, E., BROWN, J., L DRUM, C., FERGUSON, J., GARNER, S., HONIG, P. HUKKELHOVEN, M. 2012. Adaptive licensing: taking the next step in the evolution of drug approval. Clinical pharmacology and therapeutics, 91, 426. EMA. 2015. Fast track routes for medicines that address unmet medical needs [Online].   [Accessed]. EMA 2016. Final report on the adaptive pathways pilot. FDA. Breakthrough Therapy [Online]. Available: http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm [Accessed]. FDA. 2014. Fast Track [Online]. Available: http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm [Accessed]. KASHYAP, U. N., GUPTA, V. RAGHUNANDAN, H. V. 2013. Comparison of Drug Approval Process in United States & Europe. J Pharm Sci Res, 5, 131-6. MCCABE, C., CHILCOTT, J., CLAXTON, K., TAPPENDEN, P., COOPER, C., ROBERTS, J., COOPER, N. ABRAMS, K. 2010. Continuing the multiple sclerosis risk sharing scheme is unjustified. Bmj, 340, c1786. POIRIER, A. F. MURPHY, W. R. 2016. The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines. Clinical Pharmacology Therapeutics, 100, 603-605. PRASAD, V., CIFU, A. IOANNIDIS, J. P. A. 2012. Reversals of established medical practices: evidence to abandon ship. Jama, 307, 37-38. RICK, N. 2009. Drugs from discovery to approval., John Wiley & Sons, Inc. TATSIONI, A., BONITSIS, N. G. IOANNIDIS, J. P. A. 2007. Persistence of contradicted claims in the literature. Jama, 298, 2517-2526. WOODCOCK, J. 2012. Evidence vs. Access: Can Twentyà ¢Ã¢â€š ¬Ã‚ Firstà ¢Ã¢â€š ¬Ã‚ Century Drug Regulation Refine the Tradeoffs? Clinical Pharmacology Therapeutics, 91, 378-380. staggered or conditional marketing authorization AL is expected to involve a trade-off between earlier access for some patients vs. an increased level of acceptable uncertainty about benefits and risks, although the degree of uncertainty is expected to diminish with additional evidence generation. One of the main purposes of the AL scheme is to get more robust and more relevant data earlier and throughout product development. Any attempt to move toward a more adaptive approach would have to be complemented by appropriate communications to key stakeholders and assurance that the appropriate post-initial authorization capabilities exist for ongoing monitoring of medical products for which AL has been applied

Education for Students with Exceptional Needs Essay

Education is a detrimental factor to one’s success. Through formal education an individual’s knowledge is maximized and nurtured. It is because formal education hones the human mind to think critically and helps human mind in improving its decision making ability. Education also allows individuals to learn about history that enable them to better understand the present and face the challenges of the future. Education helps individuals receive information from the external world. The things people learn through formal education are the very foundation that permits them to move up in the world and seek better jobs. While it is true that hands-on-experience is an important aspect to get to the top, formal education and training are also essential to be qualified for top positions. Raw talents are important but they also need honing and the best way to hone them is through experience and assistance through schooling. Education is a must for everyone. Individuals with exceptional needs should also be given equal opportunity to learn and gain knowledge. Teaching students with exceptional needs is indeed a challenge (Adams, 2006). Teachers who wish to impart their services to these individuals should be equipped, trained, and should posses great patience and care. I believe that the experiences and learning that I am gaining from the university would significantly help me to become a better teacher for these individuals. My major helps me understand that the field of special education is an evolving and changing discipline. It is based on philosophies and it involves studying evidence-based principles and theories, which could be complicated without the guidance of experienced professors. In addition, teachers must learn how to communicate effectively with students and parents so that students will have a more enriched learning experience. I have always been taught that sharing knowledge to others is one of the best ways to help people. Teachers are heroes, they say. I do not want to become a hero but I simply want to help others. Individuals with exceptional needs have to be helped so that they could also learn to stand on their own. Giving them education is one way to support these people. It will help the students reach their full potential and give them more confidence. This will also empower parents and give them less worry regarding their children. Sincerity is an important trait of a person working for individuals with exceptional needs. I sincerely want to help them that is why I chose this field as my career. I believe that pursuing a career on the field of special education would give me the opportunity to help others. As a rehabilitation service major, I know that I will be able to impart my knowledge to these individuals and help them in my own little way. Many teachers are not very enthusiastic in pursuing a career in special education since this is a very challenging task. On the contrary, I am one of those who enjoy facing challenges. Since there are only few who choose the path on special education, I decided that I will be one of the few who could make a difference to these individuals with exceptional needs. I also believe that all people could actually learn. However, since each person is unique, appropriate instructional support is needed especially for individuals with exceptional needs. Thus, training is needed to become a suitable teacher for these individuals. That is why I highly appreciate all the things that I learn in the university because I know that the knowledge will help me in my future career.

Postmodern Cultural Studies Essay

Cultural Studies and the Academy 1. Cultural studies in the academies of the advanced capitalist countries has transformed the object of studies in the humanities. In particular, in English departments, cultural studies has challenged the predominance of the governing categories of literary studies (the â€Å"canon,† the homogeneous â€Å"period,† the formal properties of genre, the literary object as autonomous and self-contained) in the interest of producing â€Å"readings† of all texts of culture and inquiring into the reproduction of subjectivities. To this end, pressure has been placed on disciplinary boundaries, the methods which police these boundaries, and modes of interpretation and critique have been developed which bring, for example, â€Å"economics† and â€Å"politics† to bear on the formal properties of texts. In addition, the lines between â€Å"high culture† and â€Å"mass culture† have been relativized, making it possible to address texts in terms of their social effectivity rather than their â€Å"inherent† literary, philosophical or other values. 2. The two most significant categories which have supported these institutional changes have been â€Å"ideology† and â€Å"theory. † Althusserian and post-althusserian understandings of ideology, which defined ideology not in terms of a system of ideas or â€Å"world view† but in terms of the production of subjects who recognize the existing social world as the only possible and â€Å"reasonable† one, made possible the reading of texts in terms of the ways in which the workings of ideology determined their structure and uses. Marxist and post-structuralist theories, meanwhile, focused critical attention on the conditions of possibility of discourses, and upon the exclusions and inclusions which enable their articulation. In both cases, critique becomes possible insofar as reading is directed at uncovering the â€Å"invisible† possibilities of understanding which are suppressed as a condition of the text’s intelligibility. 3. I support these efforts to transform the humanities into a site of ultural critique. I will argue that what is at stake in these changes is the uses of pedagogical institutions and practices in late capitalist society. If pedagogy is understood, as I would argue it should be, as the intervention into the reproduction of subjectivities, then the outcome of struggles over â€Å"culture† and â€Å"cultural studies† will determine whether or not the Humanities will become a site at which the production of oppositional subjectivities is made possible. Historically, the Humanities has been a site at which the contradictions of the subjectivities required by late capitalist culture have been addressed and â€Å"managed. † For example, the central concepts of post-World War Two literary criticism, such as â€Å"irony,† have the function of reducing contradictions to the â€Å"complexity† and â€Å"irrationality† of â€Å"reality,† thereby reconciling subjects to those contradictions. 4. However, these recent changes in the academy have been very partial and contradictory. They have been partial in the sense that much of the older or â€Å"traditional† modes of literary studies have remained untouched by these developments, or have only made some slight â€Å"accommodations† to them. They have also been contradictory in the sense that cultural studies has accommodated itself to existing practices, by producing new modes of fetishizing texts and preserving conservative modes of subjectivity. In this way, cultural studies continues to advance the ideological function of the modern Humanities in a changed social environment. . The right wing attacks these changes, charging–as in the ongoing â€Å"PC† scare–that the Humanities are abandoning their commitment to objectivity and the universal values of Western culture. My argument is that these commitments and values have been undermined by social developments which have socialized subjects in new ways while concentrating global socio-economic power within an ever-shrinking number of transnational corporations. The intellectual and political tendencies coordinated by cultural studies, then, are responding to these transformations by allowing academic business to go on as usual, and providing updated and therefore more useful modes of legitimation for capitalist society. 6. The contradictions of these changes in the mode of knowledge production need to be understood within the framework of the needs of the late capitalist social order. The emergence of â€Å"theory† and (post)Althusserian understandings of ideology reflected and contributed strongly to the undermining of liberal humanism (in both its â€Å"classical† and social-democratic versions) as the legitimating ideology of capitalism. The discrediting of liberal humanism, first under the pressures of anti-colonialist revolts and then as a result of the anti-hegemonic struggles in the advanced capitalist â€Å"heartlands,† revealed a deep crisis in authority and hegemony in late capitalist society. This discrediting also revealed the need for new ideologies of legitimation, free from what could now be seen as the â€Å"naivete† of liberal humanist universalism, now widely viewed as a cover for racist, sexist and anti-democratic institutions. 7. The institutional tendencies which have produced the constellation of practices which can be termed â€Å"cultural studies† have, then, participated both in the attack on liberal understandings and in the development of new discourses of legitimation. The liberal humanism predominant in the academy has increasingly been seen as illegitimate because it depends upon an outmoded notion of private individuality-that is, the modern notion of the immediacy with which the privileged text is apprehended by the knowing subject. In this understanding, literature is understood in opposition to science and technology, as a site where what is essential to our â€Å"human nature† can be preserved or recovered in the face of a social reality where this â€Å"human essence† (â€Å"freedom†) is perpetually at risk. However, the more â€Å"scientific† methods (like semiology) which have undermined the hegemony of â€Å"new criticism† in the American academy, largely through the use of modes of analysis borrowed from structuralist anthropology and linguistics, have themselves been discredited by postmodern theories as largely conservative discourses interested in resecuring disciplinary boundaries (for example, through the classification of genres) and protecting an empiricist notion of textuality. 8. Cultural studies, then, is the result of the combination of the introduction of â€Å"theory† and the â€Å"politicization† of theory enabled by these social and institutional changes. However, the postmodern assault on â€Å"master narratives† (â€Å"theory†) has responded to the discrediting of both structuralism and Marxism in a conservative political environment by redefining â€Å"politics† to mean the resistance of the individual subject to modes of domination located in the discursive and disciplinary forms which constitute the subject. This has opened up the possibility of a new line of development for cultural studies: one in which the local supplants the global as the framework of analysis and description or â€Å"redescription† replaces explanation as the purpose of theoretical investigations. I will argue that the set of discourses which have â€Å"congealed† into what I

Most Common Mistakes in Essay Writing

Most Common Mistakes in Essay Writing While writing an essay, it is always good  to know the most common mistakes one makes composing  this type of paper and avoid them. Before you give your essay to the professor, make sure it is correctly written as for grammar, without  misspellings or misprints. Sometimes reading it all once again may seem to be unbearable, but force yourself to do it anyway, for it will save you from trouble. Students write most amusing things when they don’t bother to revise. If you don’t know how this or that word is written, look it up in the dictionary. It may also be a good idea to ask somebody to read it – a look from outside may find a number of mistakes that have avoided your own attention. Passive voice, though seems to be a most natural choice for writing an essay, is generally discouraged by tutors and professors for the monotony and unification of speech. It doesn’t mean that you shouldn’t use it at all (see previous sentence), but it is not a good thought to write each sentence in it. Don’t use long paragraphs. When the text is divided into a number of more or less short paragraphs, each representing a complete idea, it is easier understood and is more likely to be read attentively. Human eye is confused when confronted by a long strip of text. A very important point is not to exceed the word or page limit set for the work you do. You may think that the ingenious thoughts you want to express deserve to occupy more space, but don’t fool yourself – the committee read it all hundreds of times before and won’t be grateful for additional time spent on reading your work. Some conclusions Now you know the most frequent errors that occur while students are writing their papers. By all means, it doesnt give any guarantees that avoiding them will help you write the perfect paper. In this blog post we underlined just mistakes but didnt mention the main characteristics to follow, which can signal of the work done properly. This is another topic to be considered, but we paid your attention to the mistakes only. However, taking into consideration the tips given here will make a half of a successful job. In case you already have a draft of the work in your hands, you can check it one more time paying your attention to the guides you already know. When you see that any sentence sounds awkwardly or includes any of the mistakes we mentioned, you can rewrite it and chance at once. If no ideas come up to you, just leave it for some time. Wait until the next day if your deadline is enough for that and check the text once again. What else can help you write an essay properly? Look for other guides with tips on the most crucial steps to take, which will make your paper sound good and be done professionally. Remember that we can always help you in your essay writing. You can make a request to proofread and edit the essay you have written by yourself, or order a paper from scratch and let our writer complete an essay in any subject, on any topic, and of any size possible. A short essay can be written within three hours only, while the work of more than three pages may require some longer deadline. This is why keep this in mind to plan your budget and be in time with your final work before the due date comes. How to order with us? It is simple. Use an order form to deliver the instructions you have on the assignment to us. Upload the additional files you might have and pay for the order. After that we will find a writer and you will be able to communicate via messenger and discuss all the questions.