COVID-19 and the prevalence of drug shortages in Canada: a cross-sectional time-series analysis from April 2017 to April 2022.

BACKGROUND: In March 2020, the Government of Canada introduced measures to reduce intensifying shortages of prescription drugs during the beginning of the COVID-19 pandemic. We sought to assess the extent to which a decline in drug shortages was observed in the months after this policy change. METHODS: Our data source was the Drug Shortages Canada Database, which reports shortages by drug product, including shortage start and duration. Using a cross-sectional design, we tracked shortage rates of drug products using a 30-day moving average from Apr. 15, 2017, to Apr. 1, 2022. We used autoregressive integrated moving average modelling with a ramp function to determine the significance of trend changes after policy implementation. RESULTS: We found that of the 13 329 drug products at risk for shortage, 44.7% (n = 5953) had at least 1 shortage event in the past 5 years. Average daily shortage prevalence rates rose from 901 in April 2017 to a peak of 2345 by April 2020. Significant declines (p = 0.02) ensued shortly thereafter, dropping to a rate of 1611 shortages by the end of the first year after policy implementation. However, we did not observe a significant reduction in shortage rates in the second year (p = 0.2), with rates plateauing below 1500 and then rising back above 1600 by the end of March 2022. INTERPRETATION: Drug shortages are common in Canada, including during the initial months of the COVID-19 pandemic. We observed substantial improvements after the implementation of the new measures, but gains appear to have plateaued. Continued vigilance is needed to sustain improvements.

Premarket Development Times for Innovative Vaccines--To What Extent Are the Coronavirus Disease 2019 (COVID-19) Vaccines Outliers?

One reason expressed in surveys of people reporting coronavirus disease 2019 (COVID-19) vaccine hesitancy is how rapidly these vaccines have reached the market. To estimate the length of time the COVID-19 vaccine spent in research and development as compared to other novel vaccines, we apply previously established methods for estimating medical product development times, using the key associated patent filings cited by the manufacturer as the marker of when commercial development activity began. Applying these methods to a cohort of recently approved innovative vaccines and comparing them to the first-approved COVID-19 vaccine (BioNTech/Pfizer), we found key patent filings for the technology in this COVID-19 vaccine occurred 10.0 years prior to regulatory authorization. By this metric, the development timelines for innovative vaccines have been shortening since the 1980s, and the COVID-19 vaccine comfortably fits within this pattern. Vaccine development timelines have now even drawn to parity with many of the most commonly used drugs.

The private versus public contribution to the biomedical literature during the COVID-19, Ebola, H1N1, and Zika public health emergencies.

BACKGROUND: The private versus public contribution to developing new health knowledge and interventions is deeply contentious. Proponents of commercial innovation highlight its role in late-stage clinical trials, regulatory approval, and widespread distribution. Proponents of public innovation point out the role of public institutions in forming the foundational knowledge undergirding downstream innovation. The rapidly evolving COVID-19 situation has brought with it uniquely proactive public involvement to characterize, treat, and prevent this novel health treat. How has this affected the share of research by industry and public institutions, particularly compared to the experience of previous pandemics, Ebola, H1N1 and Zika? METHODS: Using Embase, we categorized all publications for COVID-19, Ebola, H1N1 and Zika as having any author identified as affiliated with industry or not. We placed all disease areas on a common timeline of the number of days since the WHO had declared a Public Health Emergency of International Concern with a six-month lookback window. We plotted the number and proportion of publications over time using a smoothing function and plotted a rolling 30-day cumulative sum to illustrate the variability in publication outputs over time. RESULTS: Industry-affiliated articles represented 2% (1,773 articles) of publications over the 14 months observed for COVID-19, 7% (278 articles) over 7.1 years observed for Ebola, 5% (350 articles) over 12.4 years observed for H1N1, and 3% (160 articles) over the 5.7 years observed for Zika. The proportion of industry-affiliated publications built steadily over the time observed, eventually plateauing around 7.5% for Ebola, 5.5% for H1H1, and 3.5% for Zika. In contrast, COVID-19's proportion oscillated from 1.4% to above 2.7% and then declined again to 1.7%. At this point in the pandemic (i.e., 14 months since the PHEIC), the proportion of industry-affiliated articles had been higher for the other three disease areas; for example, the proportion for H1N1 was twice as high. CONCLUSIONS: While the industry-affiliated contribution to the biomedical literature for COVID is extraordinary in its absolute number, its proportional share is unprecedentedly low currently. Nevertheless, the world has witnessed one of the most remarkable mobilizations of the biomedical innovation ecosystem in history.

Repurposing existing drugs for new uses: a cohort study of the frequency of FDA-granted new indication exclusivities since 1997.

BACKGROUND: Drug repurposing (i.e., finding novel uses for existing drugs) is essential for maximizing medicines' therapeutic utility, but obtaining regulatory approval for new indications is costly. Policymakers have therefore created temporary indication-specific market exclusivities to incentivize drug innovators to run new clinical investigations. The effectiveness of these exclusivities is poorly understood. OBJECTIVE: To determine whether generic entry impacts the probability of new indication additions. METHODS: For a cohort of all new small-molecule drugs approved by the FDA between July 1997 and May 2020, we tracked new indications added for the subset of drugs that experienced generic entry during the observation period and then analyzed how the probability of a new indication changed with the number of years since/to generic entry. RESULTS: Of the 197 new drugs that subsequently experienced generic entry, only 64 (32%) had at least one new indication added. The probability of a new indication addition peaked above 4% between 7 and 8 years prior to generic entry and then to dropped to near zero 15 years after FDA approval. We show that the limited duration of exclusivity reduces the number of secondary indications significantly. CONCLUSION: Status quo for most drug innovators is creating novel one-indication products. Despite indication-specific exclusivities, the imminence of generic entry still has a detectable impact on reducing the chances of new indication additions. There is much room for improvement when it comes to incentivizing clinical investigations for new uses and unlocking existing medicines' full therapeutic potential.

Global clinical trial mobilization for COVID-19: higher, faster, stronger.

The clinical trial landscape for Coronavirus 2019 (COVID-19) is radically different from that of previous epidemics. Compared with H1N1, Ebola, and Zika, COVID-19 had an order of magnitude more clinical trials within the first 3 months following the declaration of a Public Health Emergency of International Concern (PHEIC). These trials have started much faster, are more geographically diverse, and are less likely to be funded by industry. However, the almost simultaneous design and initiation of hundreds of trials with 0.3 million participants across 78 countries creates the potential for congestion and inefficiencies and enhances risks for investors. Thus, an international coordination mechanism for clinical trials could be valuable in this and other situations.