Structural drivers of drug shortages and market withdrawal: a longitudinal analysis of the Romanian pharmaceutical market.

BACKGROUND

Drug supply discontinuities and market withdrawals represent a general structural weakness of national healthcare systems, with direct effects on therapeutic adherence and the equity of treatment access. This study investigates the longitudinal dynamics of shortages and drug withdrawal.

METHODS

We constructed an annual dataset (2017-2024) from official national records and applied an Interrupted Time Series (ITS) analysis for shortages (as a rate adjusted to the number of Rx products), withdrawals, and SNAs, considering 2020 as the intervention point. To identify predictors of permanent shortages, we performed an observational analysis at the episode level (N = 603) and estimated a bias-reduced (Firth) logistic regression model. In parallel, we assessed the market longevity for 74,559 product-year observations (2008-2024), identifying 16,638 withdrawals and estimating a Cox model with time-dependent effects and frailty terms at the INN level.

RESULTS

The ITS outcome points to a boost in shortages before the pandemic, a sharp drop in 2020, followed by a return to the upward trend with no statistically significant change in the post-COVID slope. The lag analysis suggests that episodes of shortage precede permanent withdrawals by an average interval of approximately two years. The Firth regression shows that generic status reduces the probability of permanent shortage compared to innovative products, and ATC M and N therapeutic classes are associated with a lower probability of permanence. In the survival analysis, the risk of market withdrawal increases with intensified competition within the same therapeutic group defined by INN and with higher prices for the same active substance, and generic and biosimilar products have a higher hazard of withdrawal than innovative products, with attenuation over time.

CONCLUSION

Drug shortages in Romania reflect market fragility that predated the pandemic. The results support the necessity of moving from reactive policies to predictive surveillance and price reforms.