Microdosing (Phase 0 Trials), Adaptive Trials, Phase IV Trials and Information Technology Set to Revolutionize New Drug Development

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According to Arrowhead Publishers' new report entitled Innovations and Trends in Clinical Trials, the clinical trials industry has clear potential for strong growth in the future, driven by technological and scientific advances. This trend is complemented by the development of new trial designs, with a view to rationalizing and accelerating the drug discovery process by identifying failures at an earlier stage. Such modifications are increasingly receiving regulatory approvals and encouragement, as agencies become more aware of the benefits of such strategies.

According to Arrowhead Publishers' new report entitled Innovations and Trends in Clinical Trials, the clinical trials industry has clear potential for strong growth in the future, driven by technological and scientific advances. This trend is complemented by the development of new trial designs, with a view to rationalizing and accelerating the drug discovery process by identifying failures at an earlier stage. Such modifications are increasingly receiving regulatory approvals and encouragement, as agencies become more aware of the benefits of such strategies.

Microdosing (Phase 0 Clinical Trials) Gains Traction

Human microdosing refers to the testing of only 1 percent (or 100 micrograms, whichever is smaller) of a pharmacological dose in humans. As it provides early insight into the PK and ADME of new drug candidates, microdosing allows for unsuccessful compounds to be identified much earlier in the development process. Microdosing, therefore, allows not only for the selection of drug candidates more likely to be developed successfully, but also for the determination of the first dose for the subsequent Phase I clinical trial.

Human microdosing clearly holds significant promise as an analytical tool. In the coming years, as research methods and technology involved in Phase 0 trials become more sophisticated, human microdosing may be applied to a number of drugs that could potentially be administered consecutively. Additionally, microdosing could be useful in the discovery of endogenous biomarkers, which would assist in the quantitative evaluation of in vivo effects of drugs. The changes noticed recently in the regulatory environment will also stimulate the more frequent use of human microdosing. While it is unlikely that regulatory authorities will make the practice a mandatory requirement, given that data can be obtained by other methods, regulatory agencies may provide approval or similar incentives for companies bringing certain drugs (such as life-saving remedies) to the development and commercialization stages more rapidly.

A Future for Adaptive Clinical Trials?

Adaptive trials (also known as response-adaptive designs) are based on Bayesian statistical design and refer to statistical experiments whereby the data obtained from experiments are used to adjust the study during the course of research. More specifically, data from a trial is statistically assessed at predetermined intervals during the study.

While adaptive clinical trials clearly have a number of advantages over traditional studies, they are not commonplace at present. This situation is primarily due to their complexity, in terms of design, implementation and analysis.

Looking further into the future, the trend of combining adaptive designs with the goals of Phase IIb and Phase III trials is likely to become the norm. This type of trial, described as 'seamless adaptive', will aim to become even more time-efficient, although it may carry higher risks for first-in-class drugs.

Increasing Importance of Phase IV Trials

Phase IV are clinical trials providing the post-launch safety surveillance and support of a new drug, which can detect rare or long-term adverse effects. In some cases, Phase IV studies are required by regulatory authorities, which have become more stringent in terms of safety requirements.

Post-marketing studies are becoming more commonplace in the clinical trials landscape. The reasons behind the trend are two-pronged: on the one hand, regulatory scrutiny is requiring companies to prove the safety of their products; on the other, companies themselves are finding that Phase IV can help them circumvent costly trials associated with filings for approval for new indications of existing drugs.

Given the above factors, Phase IV trials will continue to grow at an estimated annual rate of over 20 percent. According to some estimates, companies are likely to invest over US$12 billion in this area in the course of 2007. Phase IV trials will be increasingly used to expand a drug's indications, its geographical reach, as well as to disseminate information to medical professionals, regulatory authorities and patients alike.

Information Technology in Clinical Trials

IT has a number of benefits in relation to clinical trials, including speed, ease of patient recruitment and retention, as well as the ability to collate information from a wider geographical area. The advent of the internet has particularly pushed the use of IT in clinical trials, although concerns over security, confidentiality and ethics have been raised at times.

Clinical Trials Management Systems (CTMS), Electronic Data Capture (EDC) and Clinical Data Management Systems (CDMS) are a few of the key IT tools used today in clinical trials. Electronic data capture (EDC) has become an integral component of the drug development process and all its stages. The use of information technology (IT) has allowed faster collection and analysis of all types of data, which accelerates the whole decision process related to potential drug candidates.

The trend has long been recognized, with companies emerging to specialize in the provision of IT for such purposes. The need for such data has become more pronounced by the increase of the use of adaptive designs, which requires faster responses to available information.

Over the past five years, regulatory authorities in both the US and Europe have created a number of standards regarding the use of IT in clinical trials. Such developments have pushed the utilization of IT in the field of drug development, clarifying and encouraging the situation.

Likely Future Trends in Clinical Trials

Looking further ahead, the clinical trial design will need to be modified in order to adapt to new directions in and requirements of clinical research. As Phase 0 becomes more common and more desirable, Phase I will morph into a shorter testing stage, while Phase II and III are likely to merge. The latter change would advance the trend already observed in the field, with many trials designed to test efficacy and safety of the drug at the same time.

Seamless trial designs will cut development times and associated costs. At present, the technique is most frequently used for Phase II and Phase III trials, although the Phase I and Phase II combination is also useful to prevent failures later in the clinical development process.

In the field of regulatory affairs, the FDA is waiting for the development of biomarkers to approve the use of 'enrichment' clinical trials, which would focus on a particular subgroup of patients who would be specifically responsive to a particular drug. The results of such trials have the potential to create highly targeted and effective therapeutics.

Some pharmaceutical companies are also investigating microradioactivity studies. The considered trials would maintain the pharmacological dose of the drug, but reduce by several orders of magnitude the activity in the label of compounds. The benefit of such a study would be the same results as with a regular PK study, but using radioactivity at much lower levels.

As clinical trials become more targeted, more efficient and more accurate, the pharmaceutical industry is likely to have some relief in terms of drug discovery. Most of the failures are likely to be detected in early-stage clinical trials, which will result in a significant reduction in the cost of research. Companies will, therefore, be able to maximize their capital, which will streamline the whole drug discovery process.

Arrowhead Publishers' new report: Innovations and Trends in Clinical Trials: Microdosing (Phase 0 Trials), Adaptive Trials, Phase IV Trials and the Role of Information Technology is now available. For sample pages or ordering information, please contact us at 1-612-929-5203, email us or visit our website: http://www.arrowheadpublishers.com

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