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About 10,000 papers for “Drug development”

Drug Development

Steven Findlay · JAMA · 2004

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal

Cited by 1

Drug development

John Adams · Family & Community Health · 1982

Vice President, Scientific and Professional Relations, Pharmaceutical Manufacturers, Association Washington, DC

Cited by 0

Drug Development

Corey Horien, Peijia Yuan · PubMed Central · 2017

Cited by 0Open access

Drug development

Henry Stewart Talks · ˜The œbiomedical & life sciences collection. · 2025

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DRUG DEVELOPMENT

MAIRIN BRENNAN · Chemical & Engineering News · 1996

RETURN TO ISSUEPREVNewsNEXTDRUG DEVELOPMENTTwo approaches combined to design novel class of collagenase inhibitorsMAIRIN BRENNANCite this: Chem. Eng. News 1996, 74, 44, 10Publication Date (Print):October 26, 1996Publication History Published online12 November 2010Published inissue 26 October 1996https://pubs.acs.org/doi/10.1021/cen-v074n044.p009https://doi.org/10.1021/cen-v074n044.p009newsACS PublicationsCopyright © 1996 American Chemical SocietyArticle Views8Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Pharmaceuticals Get e-Alerts

Cited by 1

Drug Development

Horien, Corey, Yuan, Peijia · PubMed Central · 2017

Cited by 0Open access

Drug Development

Yuichiro Yamashiro, Jennifer Martin, Madlen Gazarian et al. · Journal of Pediatric Gastroenterology and Nutrition · 2012

Pediatricians now need and our children deserve a more robust and effective system to avoid compromise of children's health from off-label drugs. In 2002 (1), the US Food and Drug Administration (FDA) established a new policy that, although pediatric clinical trials are not necessarily required for all new drugs, market exclusivity will be offered for pharmaceutical companies performing appropriate pediatric studies, mainly with medications that may have the potential to significantly affect children's health. In addition, the World Health Organization adopted the resolution “Better Medicines for Children” in 2007 (2). We describe recent initiatives for implementing procedures to resolve off-label drug issues. The present situation, however, remains far from satisfactory, especially in developing countries. As one of several global contributions to the 30th anniversary issue of JPGN, professionals caring for children should view this as a good opportunity to not only collect and disseminate important information worldwide but also encourage a more proactive approach in their professional activities, for example, by establishing international networks for off-label drugs to collaborate and to exchange information about new findings pertaining to standard and innovative drugs for children. TIME TO WEAN PEDIATRIC PRESCRIBING FROM OFF-LABEL TO AN EVIDENCE-BASED RESEARCH TRACK Prescribing of unapproved medicines (off-label [off-label prescribing refers to prescription of a registered medicine for a use that is not included in or is disclaimed in the regulatory body approved product information {eg, for a different indication, age group, dose, frequency, or route}] or unlicensed [prescribing an unlicensed medicine is when a medicine or dosage form of a medicine has not been evaluated nor approved by regulatory authorities for any purpose {eg, extemporaneous preparation of a formulation for pediatric use}]) is common in the pediatric population worldwide (3), and Australia is no exception (4). Up to 40% to 90% of pediatric inpatients worldwide receive at least 1 unapproved medicine during their hospitalization, with higher rates in younger and sicker patients. Use in community settings is less and most often associated with new medicines, younger ages, specialist treatment, and low-use medicines (3). Why Does It Occur and Is It a Problem? Off-label prescribing is not illegal in Australia nor is it regulated by the Therapeutic Goods Administration. Pediatric prescribers are expected to use their “professional judgment” to determine appropriateness but with often limited data to inform their decisions. This is because of insufficient medicines research conducted in the pediatric population and lack of evidence about actual and comparative efficacy, safety, and cost-effectiveness. Landmark legislative and regulatory reforms in the United States and Europe in recent years have resulted in more pediatric medicines research and improvements in licensing of some medicines for older children (5). It is disappointing that this new information is not well reflected in other parts of the world, including Australia (6), where similar reforms are so far lacking despite recent changes in the regulatory area (7). Off-label prescribing may sometimes be appropriate but is always associated with important clinical, ethical, and financial consequences, which need to be considered when assessing overall benefits and risks (3,8). There is accumulating evidence that such uses can result in harm, with increased incidence and seriousness of adverse drug reactions associated with unapproved medicines use in this population (3). Furthermore, some long-established and well-accepted off-label uses have been shown to be either ineffective or harmful when prospectively evaluated in randomized controlled trials in the pediatric population (3), for example, proton pump inhibitors. Furthermore, evidence supporting their longer-term safety is still lacking despite widespread use (9). Additional consequences of this behavior can include potential limitation of the needed medicines research agenda and withdrawal of useful (older, approved) medicines from the market because of reduced demand from newer (unapproved, and often unproven) medicines (3). Most clinicians perceive off-label prescribing as appropriate and that benefits outweigh risks; however, recent research indicates that their awareness and consideration of consequences appear suboptimal, with worrisome low level of concern about risks, unevaluated efficacy, and issues surrounding informed consent (3). Enthusiastic marketing of new medicines by the pharmaceutical industry is likely to further exacerbate the situation (10). A recent analysis of national prescribing trends for anticonvulsants in Australian children suggests that some of these factors may underlie the decrease in prescribing of older anticonvulsants, with a concurrent increase in prescribing newer anticonvulsants including off-label uses in younger children (11). In pediatric gastroenterology, monoclonal antibodies are used in Crohn disease (CD) based on demonstrated efficacy in induction and maintenance of remission; however, the safety profile is less well established, especially in the longer term. Antitumor necrosis factor (TNF) treatment is associated with a number of serious adverse reactions including infusion reactions, serious infections, tuberculosis reactivation, lymphomas, and other malignancies (12,13). These need careful consideration when making judgments about appropriate “place in therapy” for children. Such potential risks may be justifiable in refractory cases but not necessarily in early disease in which other agents with less serious toxicity may be effective. What Can We Do About It? A combination of strategies needs to be pursued concurrently (14). These strategies include more (and better) pediatric medicines research to address priority child health needs, including drug regulatory reforms, substantial commitment of public funding and dedicated infrastructure, (5,14) more systematic evaluation of the outcomes (especially safety) of unapproved medicines use, improved availability of up-to-date, objective, balanced medicines information to optimally inform prescribers about benefits and risks of unapproved medicines use, and a more systematic approach by pediatric prescribers to evaluate the appropriateness of proposed unapproved uses of new medicines. Despite many years of professional advocacy, Australia still lacks any legislative or regulatory reforms addressing pediatric medicines (5), with no dedicated resources for national infrastructure and capacity building specifically for pediatric medicines research; however there are subtle recent improvements with a pediatric prescribing information resource under development and nationally standardized decision-making framework and guiding principles for off-label use of medicines in the consultation stage (14). Furthermore, an independent national body with responsibility for implementing Quality Use of Medicines (judicious selection of management options, including choice between drug, nondrug and no treatment; appropriate choice of medicine if a medicine is considered necessary; and safe and efficacious use of medicines (http://www.health.gov.au/internet/main/publishing.nsf/content/nmp-quality.htm)) has been set up and can be supported to prioritize integration of pediatric-specific Quality Use of Medicines issues into existing and new national medicines programs. DEFINITIONS Licensing of drugs is essential to ensure safety and quality assurance. Off-label prescribing refers to licensed or registered medications being prescribed outside their license, for example, for a different indication, in a different age range, different dose or dosing regimen, or via a different route (15) An unregistered or unlicensed medicine has not been assessed or approved by the medicine registering authority of that country (15). OFF-LABEL PRESCRIBING IN PEDIATRICS Approximately 30% of hospitalized children receive off-label or unlicensed drugs; the figure may be up to 90% in neonatal units (16). All of the specialities are affected. In a pediatric gastroenterology unit in London, 49% of prescriptions were unlicensed or off-label (17). Proton pump inhibitors are commonly used off-label (in young children) or unlicensed (altered formulation) (17,18). Ethical Issues in Off-label Prescribing Off-label prescribing is not illegal and may in fact be appropriate in certain situations, provided there is no alternative and the likely benefits outweigh the potential risks. The main ethical issue in off-label prescribing relates to concerns of harm to patients (nonmalfeasance), with concerns about safety and adverse drug reactions (15). Before an unlicensed drug may be prescribed, written consent must be obtained, but this does not apply to off-label drug use. Should parents give fully informed consent for off-label medicine use in their children? Is verbal consent sufficient or should it be in writing? The majority of pediatricians in a UK study did not obtain informed consent nor did they inform the parents that they were prescribing off-label medicine (16). Informed consent demonstrates respect for parental autonomy and may protect the doctor in the case of an adverse reaction. The potential advantages of off-label prescribing include benefit to the individual patient and discovery of new therapeutic uses and collection of efficacy and safety data for medicines being used in new settings (19). Disadvantages of off-label prescribing include potential risks for both the patient (harm) and the doctor (litigation) because both the types and rates of adverse events may be different for the off-label drug. Crushing tablets may lead to potentially incorrect drug dosages. The doses of drugs licensed only for adults have to be extrapolated from adult data, with resultant incorrect dosing for children. Additionally, safety data for off-label drugs are not available when the medicine is used in different patient populations and in situations where drug–disease interactions may result (19). DRUG DEVELOPMENT FOR CHILDREN IN THE DEVELOPING WORLD There are few unique indications for medicines in children, the quantities of medication required are small, and thus the financial incentives to develop medicines for children are lacking (15,16). This has led to the description of children as “therapeutic orphans” (20). Developing world diseases are called “neglected diseases” because they do not attract pharmaceutical clinical trials. Only 1% of new drugs developed during the last 30 years are aimed at these diseases (21). Developing world diseases contributing to the high under-5 mortality rate include pediatric tuberculosis, HIV/AIDS, and malaria. In these settings, the requirements are for child-friendly drug formulations as well as formulations that can be safely stored in hot climates (21). Ethical Issues Affecting Clinical Trials in Children Trialing drugs for use in children is hampered by potential risks to the individual child and perceived exploitation of children as vulnerable subjects (22,23). Practical considerations involve different age ranges and the effects of growth and changing physiology on drug handling by child patients (23); however, giving drugs to a population of children in whom they have not been tested is potentially more harmful because the risks are totally unknown (20). Children need to be protected, but they also have the right to participate in research that has the potential to be of benefit to them. To quote Rocchi, “it is clearly preferable to test medicines in children, in a safe and controlled pediatric clinical trial environment, where the individual child is protected” (23). In conclusion, off-label prescribing of drugs in children is common, often necessary, and may well be appropriate. Every off-label prescription should be carefully assessed regarding the indications, alternative drugs, benefit-versus-risk considerations, and available evidence. If a drug is being used off-label, inform the patient and parents and, where appropriate, obtain informed consent. Clinical trials to license drugs for use in children should be regarded as an ethical imperative, and should be enforced by the regulatory authorities. ASIA In Asia, many drugs for children are used off-label or unlicensed as is the case in many other countries. Of 2032 drugs prescribed on 531,137 occasions in 1 year at 5 major hospitals in Japan, only 495 drugs (24.4%) for children had sufficient information for pediatric dosage (24). Forty percent of these drugs had the description “safety is not established in children.” Two percent were either “contraindicated” or “not recommended in children” for certain age groups. There were also ambiguous statements “the dose can be adjusted accordingly for age” or no clear guidance on usage in children in 20%. Off-label use is reported in other countries, including China (25) and Korea (26). Patients or physicians may have to import drugs that are unlicensed in their countries. Especially for oncology and genetic diseases, the cost can be more than US$10,000 annually for a person. Few drugs exist in formulations specifically for children. Extemporaneous use of drugs is common. In 32 Japanese institutions, including 18 children's hospitals, during the 4-week period in 2005, there were 1666 incidences of dosage form changes (27). In 1227 incidences, appropriate powders were made either by crushing tablets and/or adding sucrose to make different strengths. In many occasions, Japanese children take powders orally as they are or after adding a small amount of water to make them paste-like. This obviously is the reason why the dosage form changes to powder are so common. Most Japanese pharmacies have machines to automatically divide powder evenly and to pack it in sachets. In 176 incidences, tablets were divided into ≥2 sections, and in 50 incidences, syrups/suspensions were made from other forms, including IV solutions (eg, midazolam for sedation). In 40 incidences, the suppositories were cut for appropriate dosages, and in 23 incidences, inhalation solutions were made from other forms, including IV solutions. The top 10 drugs for dosage form changes on prescription number basis were warfarin potassium, methyl digoxin, enalapril maleate, dantrolene sodium, lisinopril, beraprost sodium, hydrocortisone, baclofen, chloral hydrate, and propranolol hydrochloride. Although the World Health Organization adopted the resolution “Better Medicines for Children” (2) in 2007, there is no harmonized effort among Asian countries. Some countries have started to move forward to facilitate drug development in children. In Korea, the Off-label Use Evaluation Task Force was established inside the Korean FDA in 2010, and there is continuing discussion among industries, academia, and government to solve the problems. In China, a pediatric clinical pharmacology subgroup was organized under the Chinese Pediatric Association in 2011. There is also an effort to set up a pediatric clinical trial network. In Japan, a premium for innovative drugs and for eliminating off-label use was introduced in 2009 (28). This is considered to be a strong incentive for the industries. The Study Group (Expert Panel) on Unapproved and Off-label Drugs of High Medical Need of the Ministry of Health, Labour, and Welfare are responsible for evaluating the medical need for off-label or unlicensed drugs since 2010. There is major involvement of the representatives of pediatric subspecialty societies to the activity of this study group. This was made possible because there has been a close collaboration between the Committee on Drugs of the Japan Pediatric Society and the associated subspecialty societies, including the Japanese Society for Pediatric Gastroenterology, Hepatology, and Nutrition (JSPGHAN) (29). One example of the systematic effort of academia was the approval of roxatidine, the first H2-antagonist approved for children in the country in The representatives of the the needs, and them to the clinical to and studies, and to determine the The Japan Pediatric Society and to with government and industry representatives to off-label and unlicensed drugs. One major discussion is the of similar to that in the Europe and United States that pediatric drug development to Pediatric clinical trial networks are also set up in certain including and as well as in Japanese Association of and of pediatric disease may be because of a lack of or approved medications In Europe and many drugs are not approved for use in children and are often used outside the of the approval (off-label A study from United has shown that up to of medications prescribed in a pediatric gastroenterology unit are off-label (17). One of the most on this is the use of in children with disease during the last the of agents has the management of What is because of a lack of controlled trials in children with is that pediatricians and pediatric are a when they their patients because therapeutic strategies are mainly extrapolated from adult there are drugs licensed by the US FDA to in and is also registered for use in adults with In pediatric is the only drug that has been approved by the FDA and by the Medicines and only for use in refractory however, all of the drugs have been used off-label to refractory pediatric evidence on use, data on efficacy in pediatric and information on use in pediatric have has to be effective in and use, and quality of also has a in the management of refractory pediatric data the of in pediatric The of in pediatric has to be the on in pediatric remains because most of the are and often with small patient there is an by pediatricians to use new agents in children they have been used and safely in the pharmaceutical industry does not in children and because of concerns about safety and efficacy and, not because of an concern based on the fact that children can be only a small of the potential market for a new drug. The of regulatory to ensure that and conducted in children has to this The to clinical trials in children remains a major to the use of off-label It also a to appropriate medical to our children. limited data on which to the the is at when with patients and their the potential risks of however, to trials in children are to be In the of Health and and the FDA a guidance and for pediatric for drugs and drug in children. In the for the Evaluation of an for guidance on clinical of in children. the FDA has that pediatric trials are not necessarily required for all new drugs, but it will market exclusivity for performing studies, mainly medications with a strong potential in children In conclusion, are now to children with with and, in an off-label with other however, from the use of in pediatric is early use of as a that can the of the there any genetic and/or useful for patients more likely benefit from These issues pediatric controlled trials. This can be only collaboration among worldwide pediatric to clinical trials under the Pediatric with incentives from the for Children to and develop therapeutic of in children, are responsible for in drug development and clinical trial pediatric patients. the of and written were between and marketing were approved with requirements and were between and however, both the and the are set to in Off-label use of pharmaceutical agents in the management of pediatric has been as a In by reported that only of all of the medications in the pediatric by and global regulatory including the have the of pediatric clinical trials and increased the of these trials to the appropriate and for drugs in all diseases and in all It has been reported that pediatric for drugs has improved since Despite the reported only of in the 2009 information on pediatric use in that there is still to be THE There is a need for to appropriate drug and a the approval of the in children. Drugs with pediatric for only of all the and under US pediatric research incentive the drug are for and and and on the or of available for the potential of new drug development include and including disease in and and to a few The of a study in 2007 by that, patients hospitalized at pediatric receive at least 1 medication outside the of the FDA product also that there was substantial in the of off-label product use on age and different and therapeutic Off-label drug use was with drugs the and and drugs to and a high of patients off-label treatment with and off-label use of drugs in pediatric patients in the has been reported in that of drugs used for indications are used of this off-label use was associated with is a that has in the medical community during the last there has been an increase in the reported of the and to affect a of the pediatric population is a by among different age (9). adults and are most likely to present with and and present with and to children present with and In to the of can from to of there are no for children with FOR OFF-LABEL IN respect to between professional societies such as the Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the international and other have been to for development of clinical trial As a result of these evaluation of which changes in clinical as well as of and potentially other is important during the of trials for the approval of new In addition, the development and use of in drug may important for drug development for diseases such as The further and development of potential benefits for diseases, such as which All of the in the drug development including but not limited to academia, patient and disease and regulatory must to clinical development to address off-label use of drugs the drug approval regulatory

Cited by 6

Drug Development

National Cancer Institute · Definitions · 2020

Cited by 0Open access

Drug development

Mirna Pleština · Repository of Faculty of Science · 2017

Interakcija određenih makromolekula s odgovarajućim lijekom smanjuje simptome bolesti kod ljudi. Aktivnost nekog lijeka definirana je afinitetom i specifičnošću vezanja za ciljane molekule. Unatoč tome što ovi parametri za neke ispitane spojeve mogu pokazivati zadovoljavajuće vrijednosti ti spojevi nisu nužno i potencijalni lijekovi. Osobine lijeka koje se odnose na apsorbciju, raspodjelu, metabolizam i izlučivanje označavaju se kao ADME svojstva. Lijekovi se mogu otkriti slučajno ili dizajnirati prema podatcima o prostornoj građi ciljane molekule. Saznanja o ljudskom genomu, u vidu identifikacije gena koji mogu poslužiti kao potencijalna ciljna mjesta djelovanja, znatno pridonose razvoju novih lijekova. Završne faze razvoja lijekova obuhvaćaju testiranje učinkovitosti i nuspojava na određenom uzorku dobrovoljnih ispitanika. Čak i kada se lijek odobri za primjenu na tržištu postoji mogućnost da se kod mikroorganizama i stanica raka postepeno razvije otpornost na taj lijek što predstavlja veliki problem za čovjeka.

Cited by 0

Drug Development

Karlberg, JPE · The HKU Scholars Hub (University of Hong Kong) · 2010

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Drug development

Doggrell, Sheila · QUT ePrints (Queensland University of Technology) · 2012

Cited by 0Open access