Regulators consider randomized controlled trials (RCTs) as the gold standard for evaluating the safety and effectiveness of medications, but their costs, duration, and limited generalizability have caused some to look for alternatives. Real world evidence based on data collected outside of RCTs, such as registries and longitudinal healthcare databases, can sometimes substitute for RCTs, but concerns about validity have limited their impact. Greater reliance on such real world data (RWD) in regulatory decision making requires understanding why some studies fail while others succeed in producing results similar to RCTs. Key questions when considering whether RWD analyses can substitute for RCTs for regulatory decision making are WHEN one can study drug effects without randomization and HOW to implement a valid RWD analysis if one has decided to pursue that option. The WHEN is primarily driven by externalities not controlled by investigators, whereas the HOW is focused on avoiding known mistakes in RWD analyses.

When and How Can Real World Data Analyses Substitute for Randomized Controlled Trials

The rise of antibiotic-resistant bacterial strains, causing intractable infections, has resulted in an increased interest in phage therapy. Phage therapy preceded antibiotic treatment against bacterial infections and involves the use of bacteriophages, bacterial viruses, to fight bacteria. Virulent phages are abundant and have proven to be very effective in vitro, where they in most cases lyse any bacteria within the hour. Clinical trials on animals and humans show promising results but also that the treatments are not completely effective. This is partly due to the studies being carried out with few phages, and with limited experimental groups, but also the fact that phage therapy has limitations in vivo. Phages are large compared with small antibiotic molecules, and each phage can only infect one or a few bacterial strains. A very large number of different phages are needed to treat infections as these are caused by genetically different strains of bacteria. Phages are effective only if enough of them can reach the bacteria and increase in number in situ. Taken together, this entails high demands on resources for the construction of phage libraries and the testing of individual phages. The effectiveness and host range must be characterized, and immunological risks must be assessed for every single phage.

https://www.tandfonline.com/doi/pdf/10.3109/03009734.2014.902878

Phage therapy--constraints and possibilities.

The concept of adaptive licensing (AL) has met with considerable interest Yet some remain skeptical about its feasibility Others argue that the focus and name of AL should be broadened Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development We also discuss a number of environmental changes that will enable an adaptive paradigm A life-span approach to bringing innovation to patients is expected to help address the perceived access vs evidence trade-off, help de-risk drug development, and lead to better outcomes for patients

https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.59

From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients.

Debate over the viability of the current commercial research and development (RD therefore, three reports were excluded. We extracted average pre-launch RD (2) whether the study considered potential sources contributing to the variation in RD and (3) what the components of the cost estimation were. Estimates of total average capitalized pre-launch R&D costs varied widely, ranging from $161 million to $4.54 billion (2019 US$). Therapeutic area-specific estimates were highest for anticancer drugs (between $944 million and $4.54 billion). Our analysis identified a trend of increasing R&D costs per NME over time but did not reveal a relation between cost estimates and study ranking when the suitability scores were assessed. We found no evidence of an increase in suitability scores over time. There is no universally correct answer regarding how much it costs, on average, to research and develop an NME. Future studies should explicitly address previously neglected variables, which likely explain some variability in estimates, and consider the trade-off between the transparency and public accessibility of data and their specificity. Use of our proposed suitability scoring system may assist in addressing such issues.

/pdf/how-much-does-it-cost-to-research-and-develop-a-new-drug-a-5e1awyj5yj.pdf

How Much Does It Cost to Research and Develop a New Drug? A Systematic Review and Assessment.

Policies for Use of Real-World Data in Health Technology Assessment (HTA): A Comparative Study of Six HTA Agencies

Traditional drug licensing approaches are based on binary decisions. At the moment of licensing, an experimental therapy is presumptively transformed into a fully vetted, safe, efficacious therapy. By contrast, adaptive licensing (AL) approaches are based on stepwise learning under conditions of acknowledged uncertainty, with iterative phases of data gathering and regulatory evaluation. This approach allows approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions. The concept of AL embraces a range of perspectives. Some see AL as an evolutionary step, extending elements that are now in place. Others envision a transformative framework that may require legislative action before implementation. This article summarizes recent AL proposals; discusses how proposals might be translated into practice, with illustrations in different therapeutic areas; and identifies unresolved issues to inform decisions on the design and implementation of AL.

http://www.kinexum.com/documents/Adaptive_licensing_paper_2012.pdf

Adaptive licensing: taking the next step in the evolution of drug approval.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

D. Tan

Author Tools

Chat about Author

Papers

Adaptive licensing: taking the next step in the evolution of drug approval.