Data analysis of biological proteins presents a challenge because errant points may indeed reflect the true pharmacokinetic profile of the agent under study. Thus, the most suitable PK/PD model must be used appropriately to avoid reaching a local minimum of fitting results. Pegylated interferon α-2a (PEG-IFN) is interferon α-2a in which one branched polyethylene glycol molecule is conjugated. The half-life of interferon increases upon pegylation and the absorption is sustained, thereby providing greater exposure and the expectation of greater efficacy with just weekly administrations. Four different absorption models were compared in the present study to establish a PK/PD model for PEG-IFN and provide an optimal dosage guideline, where 2', 5'-oligoadenylate synthetase (2', 5'-OAS) is used as the PD marker. An indirect response model (stimulation-k_in⁰) was used to describe PD of PEG-IFN, i.e. 2', 5'-OAS activity.
A first-order absorption model was concluded to be the best absorption model to describe PK/PD of PEG-IFN and 2', 5'-OAS activity. The PK of PEG-IFN can be described by a linear process. The mean EC₅₀ at a dose of 180 μg was one-third of its C_max (ca. 10 ng/mL) which may indicate that 180 μg is the clinically optimal dose because the serum level of PEG-IFN at a dose of 180 μg sustained above EC₅₀ for long time in comparison with the case at a dose of 90 μg and 2', 5'-OAS activity reached a plateau level at a dose of 180 μg, although 2', 5'-OAS activity has not been validated as a surrogate marker of clinical activity.
The current PK/PD model well describes the enhanced PD effect, i.e. 2', 5'-OAS induction, as a consequence of the enhanced PK exposure of PEG-IFN. These results confirm the value of applying the PK/PD modeling approach to support the clinical development of potential products.

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In the diagnosis and medical treatment guideline of Helicobacter pylori (Hp) infection, atrophic gastritis is examined as one of the diseases that Hp eradication medical treatment is meaningful, and it is said that a large scale intervention examination is required.
This research was conducted using the immune serum diagnostic method of and Hp IgG antibody and pepsinogen (PG) regarding the selection of atrophic gastritis used as Hp eradication object. In the results, serum PG I /II ratio of PG positive atrophic gastritis which shows Hp infection had a more significant decrease than PG negative diseases, and presented similar serum PG I / II ratio as PG-positive gastric cancer or gastric-duodenal ulcer. Therefore, when choosing atrophic gastritis used as Hp eradication object, it was thought useful to use the serum pepsinogen method.

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The major factors that have heretofore prevented an efficient implementation of clinical trials include deviations from the protocol at the investigator's site, defectiveness in filling out the case report forms (CRFs), frequent monitoring and fixing work of patient data by the sponsor, handwritten preparation of various documents, and so on.
As an experiment in electronic implementation of an efficient clinical trial utilizing information technology, we formed an electronic data capture (EDC) system that efficiently collects clinical data from the investigator's site, and applied it to a clinical trial. As a result, there was no patient with a GCP violation and thus all were eligible as study subjects and the number of correction log form (CLF) for CRFs was considerably reduced. In addition, it was possible to conduct an efficient clinical trial and shorten the study period by utilizing this EDC system. We discuss the future readiness for clinical trials based on this experience of implementation, as well as the challenges that lie ahead.

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