Therapeutic Innovation & Regulatory Science

While the shift to digital technologies is pervasive across multiple industries, the informed consent process for clinical trials remains largely paper-based. Given the inefficiencies in the traditional process and the increasing complexity of clinical studies, the current approach at times may raise challenges with respect to quality, compliance, participant understanding, and trial retention. Electronic informed consent (eConsent) is an enabling clinical technology to potentially address these issues by using multimedia components to create an interactive participant experience and improve data quality.

The TransCelerate eConsent Initiative conducted a multifaceted engagement approach to better understand the perceptions, experiences, and concerns of impacted stakeholders, including participants, sites, ethics committees, and health authorities.

While all stakeholders were supportive of the use of multimedia components to deliver study information, several stakeholder-specific concerns were noted. Participant feedback, as collected through surveys (n = 3045) and an advisory board (n = 10), suggests that some participants may have data privacy concerns and a diversity of preferences for multimedia presentation. Site interviews (n = 9) suggest concerns related to additional operational activities and potential for technology failure. Health authorities’ feedback, through nonbinding meetings, was geographically varied; ethics committee feedback, through interviews, suggests concern over impact on operational process changes.

While the appetite for eConsent is increasing, involved stakeholders and industry must continue to raise awareness, communicate, and collaborate to develop appropriate technological capabilities, regulatory pathways, and operational processes to clear the path for mainstream use of eConsent.

Over the past decade, the volume of adverse events (AEs) reported to marketing authorization holders and regulators has been rapidly increasing each year, which has led to significant challenges in patient safety assessment. Three data sources that have largely contributed to the expansion in adverse event reports are patient support programs (PSPs), market research programs (MRPs), and social media. In this study, we sought to further understand the contribution of these safety data sources to the characterization of a product’s safety profile.

Three separate approaches were taken that, when combined, can be used to evaluate each data source. The first identified any core company data sheet changes or drug safety label changes. The second evaluated the similarity of information through proportions of AEs between each solicited data source and spontaneous sources. Lastly, the completeness of information reported was evaluated through vigiGrade and compared across each data source.

One drug safety label change was identified from a patient support program, which involved regular contact with health care providers. No label changes were identified from market research programs or social media. Patient support programs, market research programs, and social media report similar proportions for HLGT as spontaneous sources. Market research programs and social media display very low vigiGrade scores. When broken down by subtype, traditional PSPs display high vigiGrade scores, while patient assistance programs display lower vigiGrade scores that were program dependent.

This study did not demonstrate that certain data sources such as market research programs, social media, and patient assistance programs meaningfully contributed to the further understanding of the characterization of a product’s safety profile.

Biological therapies are increasingly common in the United States. Although their clinical development may deviate significantly from the classic paradigm used for small molecule drugs, there has been little systematic analysis of these programs. We describe the development programs and factors associated with approval in the first review cycle for biologics approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research (FDA CDER) between 2003 and 2016.

We conducted a retrospective analysis of publicly available approval packages including clinical pharmacology/biopharmaceutics, medical and summary reviews, and approval letters for biologics approved by FDA CDER. We evaluated characteristics of the development program (eg, use of expedited pathways, clinical pharmacology studies, number and type of pivotal trials) and the prevalence and correlates of first cycle approval, a key indicator of successful product development.

We assessed 81 development programs for 75 unique therapies. Most programs (67%) made use of at least 1 expedited designation and about half (49%) were designated as orphan products. The clinical pharmacology programs were highly variable and one in four (25%) did not include an ascending dose study, where the tolerability of the therapeutic is typically determined before pivotal trials. Since 2003, an increasing proportion of biologics have been approved on first cycle approval and with fewer than 2 pivotal clinical trials (P < .001 for trend). Of the approximately three-fourths (76%) of products that were approved on the first review cycle, the likelihood of such approval was greater among development programs that performed an ascending dose study (84% vs 55%, P = .01) or held an End of Phase 2 meeting (85% vs 57%, P = .01).

Considerable regulatory flexibility, with respect to the number of pivotal trials and data supporting dosing, coincides with a growing number of biologics approved on an annual basis.

Pharmaceutical companies rely on regulatory intelligence (RI) to analyze information from internal and external sources. To facilitate RI activities, companies are seeking ways to harness technology to optimize their capabilities. Specifically, there is a growing interest for artificial intelligence (AI) to enhance RI activities. However, exploration of the potential utility of AI and related technologies will be key to begin unlocking these tools for the regulatory community.

To identify potential development paths for these technologies, we interviewed over 30 global regulatory leaders at 22 pharmaceutical companies and 3 leading companies in RI and AI technologies. Thirteen of the 22 pharmaceutical companies also provided responses to a subsequent informational survey.

This study elucidated potential value proposition, barriers, and risks to integrating AI into the RI field. Twenty of the 22 participating companies consider that AI offers significant opportunity for RI activities of data processing (mining, searching, monitoring, alerting). Thirty-two percent of companies envisage use in data synthesis (combining different types of information across formats), 36% in data analysis (trends, patterns, predictive analytics), and 23% in decision making. Additionally, results of this research provided insights about the potential role of precompetitive consortia, which may enhance future actualization.

Opportunity presents for AI to enhance quality, speed, and efficiency of RI activities. This assessment of the current technology landscape revealed a lack of fully developed AI tools; however, the RI community demand is beginning to be recognized. Therefore, now more than ever, the timing to advance AI within the RI field is right.

In Japan, different regulatory tracks prior to marketing have been applied to medical devices dependent on whether they have predefined certification or approval standards in addition to the risk category. A regulatory track for some high-risk medical devices (class III or IV in Japan) using certification standards newly became effective in 2014. This study aimed to explore potential candidate devices for the certification track.

We analyzed approval, recall, and classification information databases for medical devices in Japan. High-risk medical devices approved between 2010 and 2014 were examined (N = 3222). The medical devices were categorized into 3 groups based on availability of certification or approval standards. Recall rates were calculated for each group and for each device category within the groups. Recall reasons were classified into two main categories: design problems and other problems.

The overall recall rates were 12.1% in the group with certification standards (recalled n = 17, approved n = 141), 4.1% in the group with approval standards (recalled n = 49, approved n = 1187), and 5.6% in the group without either standard (recalled n = 106, approved n = 1894). The design recall rates were 9.2%, 1.4%, and 1.6%, respectively. The recall rate for bio-phenomena-monitoring devices was high (recalled n = 13, approved n = 31; 41.9%), which contributed to the high recall rate of the group with certification standards.

The overall recall rates and the recall rates due to design problems varied considerably across and within the 3 groups. As possible good candidates for the transition into the new certification track, high-risk medical devices with low recall rates in frequently approved device categories should be given priority.

International accreditations of drug regulatory authorities not only lead to improvement in their functioning but pharmaceutical firms are also benefited. The aim of this study is to identify aspects that should be improved for the purpose of international accreditation and recognition of Drug Regulatory Authority of Pakistan (DRAP).

A qualitative study was conducted from May 1, 2017, to July 31, 2017. The data were collected from officials working in DRAP through in-depth semistructured interviews. The respondents were recruited through a convenience sampling strategy. The sample size was determined by using the saturation point criterion. Data were analyzed to draw conclusions using inductive thematic analysis.

A total of 12 officials working in DRAP were interviewed. Analysis of the data yielded 25 categories, 10 subthemes, and 3 themes. The themes were administrative barriers, operational barriers, and future aspects of international accreditation. The subthemes related to administrative barriers included human resource, lack of harmonization and coordination, transparency and accountability, and improper resource allocation. The subthemes related to operational barriers included procedures and policies, deficit of testing laboratories and equipment, reporting system for adverse drug reactions, and external factors influencing the functioning of DRAP. The subthemes related to future aspects of international accreditation included advantages associated with international accreditation and time required to achieve this goal.

There is a huge scope of improvement in the functioning of DRAP and the identified barriers must be dealt with timely to make it happen.