Therapeutic Innovation & Regulatory Science

Acne vulgaris, a chronic inflammatory disease, is among the most common dermatologic conditions worldwide. In Saudi Arabia, Isotretinoin is commonly used to treat mild acne even without prescription.

To explore the practice and knowledge of community in Saudi Arabia regarding dispensing, counseling practices, and safety of isotretinoin-containing products.

A cross-sectional survey, using a self-administered questionnaire, was conducted in 3 sections: demographics, self-medication attitude (in the form of self Isotretinoin use), and identifying the side effects associated with the use of isotretinoin.

A total of 1069 participated in the study. Around half of the participants (44.2%) used isotretinoin with only mild acne as their first choice, which is contrary to the recommended guidelines. Virtually one-fifth of the participants did not examine the lipid profile, liver enzymes, and blood glucose level before isotretinoin use. Not many participants identified lipid (58.7%) and liver (44.1%) depression (53.3%), inflammatory bowel disease (75.9%), osteoporosis (60.3%), and sunburns (36.3%) as risks allied with isotretinoin use. Most participants (88.9%) appropriately recognized teratogenicity as the greatest hazard concomitant with the use of isotretinoin. Nevertheless, 20% of the women did not know that they must cease the drug at least 6 months before pregnancy.

This study shows that community residents are not satisfactorily aware of the proper use and jeopardies of isotretinoin. Therefore, greater consideration ought to be dedicated to augment the safe use of isotretinoin. We recommend the implementation of tools to enhance the safe use of isotretinoin and the imposition of more effective regulations to limit nonprescribed isotretinoin dispensing in Saudi Arabia.

The gold standard in conducting clinical trials/studies is to follow what is prespecified in the study protocol. However, deviations from the study protocol may occur. This article discusses the issues of protocol deviation in pivotal clinical trials or studies for medical device and provides statistical approaches to mitigating bias such as selection bias specifically for diagnostic test clinical trials or studies.

Bias correction methods are developed for 2 specific types of selection biases, prescreening bias and verification bias. Statistical approaches are discussed on how to estimate device performance adjusted for enrollment enrichment and discrepant testing results. We use an FDA-approved Roche Cobas Human Papillomavirus (HPV) test for detecting high-grade cervical disease (>CIN2) as an example to illustrate how to correct for verification bias. A recently FDA-cleared Microarray Assay in detecting copy number variation is used to illustrate how to properly estimate sensitivity and specificity for the discrepancy analysis.

The unadjusted sensitivity and specificity based on verified samples were 83.2% and 60.4% for the Roche’s HPV test. However, using the correction method with the missing-at-random assumption, the verification bias–adjusted sensitivity and specificity were 34.5% and 93.6%, respectively.

Protocol deviations can lead to biased estimates of device clinical performance if not handled appropriately. Statistical methods correcting for bias and protocol deviations are recommended in estimating device performance.

Clinical trials should be part of routine health care. There is a common perception that enrolling patients into clinical trials results in additional costs. We conducted a retrospective cost analysis to compare medical costs attributable to participation in cancer treatment trials versus standard of care in a single Spanish institution.

Patients recruited into cancer clinical trials between 2014 and 2016 were selected. Each research protocol was reviewed to identify trial-associated medical procedures and costs, as well as the equivalent care had the patient not been entered in the trial. Treatment cost difference was the difference between the cost of the clinical trial and that of the standard of care.

A total of 68 adult patients were treated in 20 different clinical trials. The overall cost treatment of the patients included in the trials was 79% lower in comparison to the standard of care. However, the load of medical procedures was 32% higher. The average treatment cost per patient and protocol ranged from an excess of €8193 to a saving of €59,770.

There is a wide range of difference in treatment costs for cancer clinical trial participants versus standard of care. Commercial trial protocols were associated with larger savings compared with the noncommercial ones, even though these may involve excess treatment costs. Overall, clinical trials provide not only the best context for progress of clinical research and health care but also creates opportunities for reducing cancer care costs.

Entry into a new therapeutic area, that is, one in which a pharmaceutical firm lacks experience, is a considerable challenge for firms that need to overcome scientific and technological barriers. To address this issue, the present study aims to explore the potentiality of alliances in an empirical manner.

From the clinical trials sponsored by 20 major pharmaceutical firms during 2008–2016 listed at ClinicalTrials.gov (n = 14,941 clinical trials), cases of entering a new therapeutic area for a pharmaceutical firm were extracted (n = 73), followed by statistical analyses to evaluate the effect of alliances in this regard.

We found that the average number of participating organizations in the cases of entering a new therapeutic area was significantly larger than that in the cases of entering an area in which firms had experience (P < .01), suggesting that alliance has a positive effect on new therapeutic entry for these pharmaceutical firms. Second, we found that the cases of partnering with nonindustrial or nongovernmental organizations (ie, universities, research institutes, hospitals, funding agencies, and others; n = 32 of the 73) were significantly associated with these new entry trials (adjusted odds ratio = 1.1, P < .05). Furthermore, we identified that 10 of the 32 clinical trials were associated with rare diseases, which is an overrepresentation compared to the occurrence in the universe (1015 of the 14,941; P < 10^–5).

These findings strongly suggest the importance of alliances with diversified partners in new therapeutic entry and also provide a basis for further detailed investigation of key success factors for pharmaceutical firms.

The Pharmaceutical Medicine program at the University of New South Wales provides postgraduate education for students seeking employment relating to development of new medicines and medical technology. The objective of this study was to determine which changes to the program were required to meet future educational needs of students.

Responses to questions from 76 students, tutors, lecturers, and stakeholders were obtained via Qualtrics surveys.

Most respondents would recommend the program because of scope and program emphasis, content, quality of teaching, flexibility, and availability of distance and online content. Students valued links to industry and the national regulatory authority. Respondents recommended program content be current, expanded to meet needs of the Asia-Pacific region, and structured to ensure opportunities for networking and collaboration.

Recommended changes to the program are being implemented to optimize skills and knowledge of graduates for roles in global pharmaceutical, medical technology, and biotechnology industries.

Development of novel dermatological topical products for the treatment of cutaneous fungal infections is a constant necessity, especially in developing countries. Through public health policies, many developing countries have facilitated in the last decades the entry of generic products, which can be superficially seen as a threat to innovation. To verify whether regulatory requirements, or the waiving of some requirements, could have an impact on innovation, we performed a detailed technical comparison of the dermatologic antifungal markets of Brazil and of the United States, taking Brazil as an example of a developing country with more lenient requirements regarding the registration of generic topical drug products.

The official databank of ANVISA (DATAVISA) and of US Food and Drug Administration (Orange Book) were assessed for valid topical dermatological antifungal drug products registered.

The Brazilian market has a greater number of registered drug products encompassing a greater variety of drug substances than the US, but the latter comprises more products with novel technologies. In both countries, cream was the predominant dosage form and imidazoles were the major substance group. Ketoconazole was the lead active substance in Brazil and ciclopirox was the lead drug in the US. Generic products dominated both markets.

Despite the great number of registered products, the Brazilian market lacks the latest technologies, reflecting that the ease of generics registration is not accompanied by innovation.

Little is known about the Canadian public’s perspective regarding clinical trials.

We surveyed 1602 Ontario and British Columbia residents to ascertain their understanding of and willingness to participate in clinical trials.

Clinical trials are regarded positively with overall perceptions that they provide societal and personal benefits. Most respondents were somewhat (49%) or very willing (19%) to participate in a clinical trial. This increased with age and level of education. It was also greater among those with poor or very poor health, those with multiple chronic conditions, and those who had previously been invited into a clinical trial, all of which were correlated with age. Still, there was room for improvement in awareness and understanding of clinical trials. Forty-three percent of those surveyed felt not very informed or not at all informed and 37% had no opinion regarding clinical trials. Respondents would most often turn to their treating physician if considering participating in a clinical trial and least often to social media.

While Canadians’ views about clinical trials are generally positive, they are somewhat muted and a significant minority feels poorly or not at all informed. They are less willing to participate in clinical research than Americans and are roughly equivalent to Europeans. While clinicians are the top choice for learning about clinical trials, they have little or no training and little time for this role. As we move toward integrating clinical trials into the practice setting, these issues of time, training, and resources must be addressed.

This study was aimed to examine the number and employment conditions of clinical research coordinators (CRCs) in Korea, with comparison to data from 2010 to identify changes.

The descriptive study examined 65 sites that participated in a survey or phone interviews among 184 sites registered as clinical trial sites by the Ministry of Food and Drug Safety, and 2 site management organizations. The data were analyzed for mean, standard deviation or median, range, frequency, and percentage.

There were 2855 CRCs in 65 sites and 3711 CRCs nationwide, which reflected an increase of 268 people every year on average since 2010. The most common employment system (60.6%) was where CRCs were hired by sites and allocated to clinical trial departments. As for employment type, 48.5% of posts were full-time, and monthly wage payment was the most common at 54.5%. An employment/personnel management department was reported at 87.9% of sites. The average duration from hiring to resignation was 19 months.

The number of CRCs was increased, and such an increase of CRCs was attributed to the increase of investigator-affiliated CRCs rather than site-affiliated CRCs. Though the employment conditions of CRCs have been improved, most improvements were confined to site-affiliated CRCs. It is recommended that each site have a CRC registration and management system for both site-affiliated CRCs and investigator-affiliated CRCs, standardized CRC employment guidelines, and support for CRCs to participate in the training program for the overall improvement of employment conditions of CRCs in Korea.

It is important to examine how a usual drug dose is established in Japan and other countries, and to evaluate that on the basis of pharmacokinetic and pharmacodynamic properties. In the present study, we examined the contributions of area under the curve (AUC) ratio and other factors on differences of usual dose between Japan and the United States.

We examined drugs approved from January 2008 to January 2011 in Japan and collected related information. For the usual dose set for the same indication in both countries, we compared the maintenance dose values between the countries. We also examined the relationships of AUC ratio and difference of usual dose in both countries.

Our results clarified that the usual dose for the same indication is comparable between Japan and the United States for 68.75% of the examined drugs, while that for 31.25% is different. Moreover, among products with different approved doses, the dosage was set higher in the United States for 18.75% and higher in Japan for 12.50%. Our findings indicate that the difference in dose between the countries is associated with AUC ratio for 82.1% and by factors other than AUC ratio for 17.9% of the examined medications.

The approved dose varies between the countries for about one-third of products commonly used. Additionally, it was clarified that not only AUC ratio but also other factors are involved in dosage differences. The present results provide useful information for analysis of factors related to the different usual doses between countries.

Clinical research coordinators (CRCs) are persons who collect, record, and maintain clinical trial data in accordance with the principles of Good Clinical Practice at investigators’ sites. This study was conducted to examine attitudes of clinical research coordinators (CRCs) toward risk-based monitoring (RBM) prior to full-scale implementation of RBM in Korea.

The study subjects were 607 CRCs, and data were collected using a self-reported questionnaire. Collected data were analyzed by frequency, percentage, χ² test and Fisher exact test.

Among CRCs, 42.3% had heard of RBM and 44.6% were found to oppose its implementation. Those opposed believed that implementation of RBM would increase the workload of CRCs and CRAs’ work support for CRCs. In addition, they showed many negative opinions such as poor accuracy of test data input and failure to increase the overall quality of clinical tests. In particular, such attitudes were more noticeable in CRCs with 5 or more years of experience.

Before the implementation of RBM, it is necessary to come up with administrative measures such as education for practitioners and recruitment of human resources to help CRCs properly understand RBM.

The basis for this article is an individual project during a Master of Science program at Cranfield University, UK. Research and development (R&D) costs in the pharmaceutical industry have increased at a rate where costs have doubled compared to previous decades since the 1980s. In parallel, during recent years, there has been an increased focus on quality management within clinical development. Furthermore, pharma companies are talking about quality as a competitive advantage with an increased focus on quality metrics. The objective of this research was to confirm/reject the assumption that costs of quality are not being tracked within clinical development.

The key component of this research consists of a survey that was sent out to approximately 15 of the top 50 global pharmaceutical companies.

The research showed that the praxis of tracking and analyzing costs of quality was not widespread within clinical development, although the tools are available and experience from other industries showed that there are potential benefits to be realized, including a reduction of total quality costs.

Even though tools for analyzing costs of quality have been available since the 1950s, there is little evidence in the literature that quality costs are being tracked and analyzed in clinical development. On the contrary, there are examples that the clinical research part of the pharma industry is stuck in traditional ways of working. However, it is likely that tracking and analyzing costs of quality can help limit the increase of R&D costs.