Phase 0 Clinical Trials and other trends

The clinical trials industry is growing at a rapid pace , driven by technological and scientific advances. New trial designs are being designed with a view to rationalize and accelerate 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 and one such is Phase 0 Clinical Trials.
Microdosing, or human phase 0 clinical trials, is a technique whereby subpharmacological doses of prospective drug candidates are administered to human volunteers. A microdose study provides early pharmacokinetic data in humans and only requires minimal preclinical toxicology safety testing. A microdose is defined as 100th of the pharmacological dose (or predicted pharmacological dose) or a maximum of 100μg. Microdosing is a relatively recent innovation and there remains a degree of uncertainty as to whether such a small dose will adequately predict the pharmacokinetics of the therapeutically active dose.
It is believed that Human microdosing helps in reducing the costs and time spent on clinical trials especially in the fields like oncology. 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.
Post-marketing studies are also 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 TrialsIT 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 but with advances made in technology most of the apprehensions raised by Pharma industry have been addressed.
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.
Likely Future Trends in Clinical TrialsLooking 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.