Driving clinical study efficiency by using a productivity breakdown model: comparative evaluation of a global clinical study and a similar Japanese study.

WHAT IS KNOWN AND OBJECTIVE: A fundamental management imperative of pharmaceutical companies is to contain surging costs of developing and launching drugs globally. Clinical studies are a research and development (R&D) cost driver. The objective of this study was to develop a productivity breakdown model, or a key performance indicator (KPI) tree, for an entire clinical study and to use it to compare a global clinical study with a similar Japanese study. We, thereby, hope to identify means of improving study productivity. METHODS: We developed the new clinical study productivity breakdown model, covering operational aspects and cost factors. Elements for improving clinical study productivity were assessed from a management viewpoint by comparing empirical tracking data from a global clinical study with a Japanese study with similar protocols. RESULTS: The following unique and material differences, beyond simple international difference in cost of living, that could affect the efficiency of future clinical trials were identified: (i) more frequent site visits in the Japanese study, (ii) head counts at the Japanese study sites more than double those of the global study and (iii) a shorter enrollment time window of about a third that of the global study at the Japanese study sites. WHAT IS NEW AND CONCLUSION: We identified major differences in the performance of the two studies. These findings demonstrate the potential of the KPI tree for improving clinical study productivity. Trade-offs, such as those between reduction in head count at study sites and expansion of the enrollment time window, must be considered carefully.

Gaps in the information shared on consumer healthcare products.

We conducted a questionnaire survey of visitors to the Japan Drugstore Show 2006 and an additional questionnaire survey of pharmacists in 2008 to ascertain the current information gaps between consumers and manufacturers of consumer healthcare products (CHPs). Three main gaps were apparent: first was a gap between information that consumers wanted to receive and information that was widely disclosed by manufacturers of CHPs, second was a gap between the advisors whom consumers regarded as appropriate and the advisors who consumers had actually consulted, and a gap between what consumers expect pharmacists to know and pharmacists' actual knowledge. Manufacturers' efforts alone will not be able to close these gaps because of the number of regulations. Thus, a new social system should be constructed to supply adequate information on CHPs and consumers should enjoy free access to this information.

Analysis on productivity of clinical studies across -- Asian countries a case comparison.

In an era of increasing global competition and an increased interest in global clinical studies Japan has been concerned with the risk of losing its attractiveness due to perceived longer execution times and higher cost structure. In contrast, other Asian countries particularly China and Singapore are widely recognized as potential key centers for fast conduction of global clinical studies. We conducted a case comparison based on two clinical studies performed by a multinational pharmaceutical company in order to measure the productivity of clinical studies by region and country. We focused on the site-related study cost which constituted the largest portion of the cost breakdown and also impacted both time and quality management. For investigation of the productivity we propose a breakdown model with two Key Performance Indicators (KPIs), enrollment efficiency and site-related cost efficiency, for the comparison of the number of enrolled subject per site and cost, respectively. Through the comparative analysis we found that the Asian countries (excluding Japan) on average achieved higher efficiency than Japan in both indicators. In the Asian group, China and Singapore stood out as the most efficient on both speed and site-related cost. However, when the site-related cost efficiency was adjusted for Purchasing Power Parity (PPP) the cost advantage in China disappeared, implying the price level was critical for productivity management. Although quality aspects remain to be investigated we postulate that introducing a comparative approach based on a productivity framework would be useful for an accurate productivity comparison.

Axonal projection of olfactory sensory neurons during the developmental and regeneration processes.

We have studied the projection of olfactory sensory neurons (OSNs), during the developmental and regeneration processes, using the transgenic mouse carrying the differently tagged odorant receptor genes, MOR28. We have found that the axon terminals of the two sets of MOR28-positive OSNs, one expressing the lacZ tag and the other expressing the green fluorescent protein gene, are dispersed and intermingled at early developmental or regeneration stages. Projection areas become more distinct and separated at later stages, however, two sets of axon fibers are not typically bundled or segregated during pathfinding. It appears that segregation of axons mainly occurs when they target at the olfactory bulb to form the glomerular structure.

Functional identification and reconstitution of an odorant receptor in single olfactory neurons.

The olfactory system is remarkable in its capacity to discriminate a wide range of odorants through a series of transduction events initiated in olfactory receptor neurons. Each olfactory neuron is expected to express only a single odorant receptor gene that belongs to the G protein coupled receptor family. The ligand-receptor interaction, however, has not been clearly characterized. This study demonstrates the functional identification of olfactory receptor(s) for specific odorant(s) from single olfactory neurons by a combination of Ca2+-imaging and reverse transcription-coupled PCR analysis. First, a candidate odorant receptor was cloned from a single tissue-printed olfactory neuron that displayed odorant-induced Ca2+ increase. Next, recombinant adenovirus-mediated expression of the isolated receptor gene was established in the olfactory epithelium by using green fluorescent protein as a marker. The infected neurons elicited external Ca2+ entry when exposed to the odorant that originally was used to identify the receptor gene. Experiments performed to determine ligand specificity revealed that the odorant receptor recognized specific structural motifs within odorant molecules. The odorant receptor-mediated signal transduction appears to be reconstituted by this two-step approach: the receptor screening for given odorant(s) from single neurons and the functional expression of the receptor via recombinant adenovirus. The present approach should enable us to examine not only ligand specificity of an odorant receptor but also receptor specificity and diversity for a particular odorant of interest.

[Four cases of noncardiac surgery after PTCA].

Malignant tumors were detected in four patients who had been hospitalized for acute myocardial infarction and/or postinfarction angina. All of them underwent curative operations after successful percutaneous transluminal coronary angioplasty (PTCA). Operations performed were partial colectomy on the first patient, low anterior rectal resection on the second patient, left pulmonary upper lobectomy on the third patient and partial colectomy with cholecystectomy on the fourth patient. There were no complications in the perioperative periods except the first patient in which postoperative electrocardiogram showed transient peaked T wave in leads II, III, AVf, V5 and V6. Forty six days after colectomy (55 days after PTCA), the first patient underwent emergency PTCA for restenosis. Prior PTCA, as well as CABG, is considered to have decreased cardiac complications in patients with ischemic heart disease. But when a non-cardiac operation should be done after PTCA, we should take restenosis into consideration.