A key step in developing a new drug is the transition from the laboratory to the human subject in a Phase I clinical trial, where the new compound is given to humans for the first time. A Phase I trial is the gateway between scientific research and clinical medicine. Generally, in-human Phase I studies are conducted in healthy male patients or healthy male volunteers; however later Phase I-Ib trials are conducted in-human with the affected disease the compound is intended to treat.
Phase I studies are tested in a small group of people for the first time to evaluate the new drug’s safety, safe dosage range and side effects. Once tested, the results obtained by the patient will convey how the compound is absorbed, distributed, metabolized and eliminated from the body. Additionally, these trials identify preferred routes of administration (e.g. tablet, liquid or injection) and can determine the appropriate doses for later Phases.
These studies are conducted in Phase I units which are generally based within hospitals providing on-site lab facilities to process and store time critical pharmacokinetic and pharmacodynamics samples; back up equipment such as freezers and backup generators, direct emergency room availability with access to doctors and highly experienced nurses. The use of these facilities can ensure a high standard of patient safety and sample protection whilst offering a suitable environment when performing first-in-human and other Phase I safety studies.
Later Phase Ib in-patient studies, where the new drug is ordinarily conducted in patients diagnosed with the disease, will help demonstrate a biomarker, surrogate or possibly a clinical outcome that is considered for proof-of-concept. Furthermore, the proof-of-concept in a Phase Ib trial may confirm the hypothesis of the current prediction of biomarker or outcome benefit is compatible with the mechanism of action.
These trials are also conducted in Phase I units. However, as in-human Phase I-Ib trials require patient referrals from a hospital or clinic to a Phase I unit, CROs play a vital role to the study conduct in partnership with a Phase I unit. CROs carry out a variety of services associated with the clinical research process such as: medical writing, selecting suitable and qualified investigators for the trials, data analysis, clinical management and regulatory support.
Throughout a study, CROs collaborate with various sites; notifying them of an upcoming trial along with subject requirements that meet protocol specifications. Once sites have been notified of the trial, patients are screened by the sites and referred to the Phase I unit participating in the study. The CRO then monitors the patients and manages the activities at the Phase I unit (as if it was a clinical site). The responsibility of the Phase I unit is to treat patients in accordance with the protocol, entering patient data into the data capture system, managing on-site responsibilities and provide patient safety.
The number of Phase Ib studies are on the rise as it presents an opportunity to test the drug’s possible effectiveness before launching into a larger and riskier Phase II trial. Clinicaltrials.gov recorded 89 Phase I studies in 2010 globally, with a dramatic increase of 1825 trials in just 4 years. More parties are involved in the conduct of a Phase Ib study, as opposed to a Phase I study, as it includes the Phase I unit, CRO and referring sites. To be successful, a thorough collaboration between the parties are required and therefore, is best managed by CROs who possess the necessary experience, scientific expertise and network to manage clinical trials across multiple institutes, research units and sites.