Dataset Information

Health Canada's use of expedited review pathways and therapeutic innovation, 1995-2016: cross-sectional analysis.

ABSTRACT:

Objectives

This study examines the use of expedited approval pathways by Health Canada over the period 1995 to 2016 inclusive and the relationship between the use of these pathways and the therapeutic gain offered by new products.

Design

Cross-sectional study.

Data sources

Therapeutic Products Directorate, Biologics and Genetic Therapies Directorate, Notice of Compliance database, Notice of Compliance with conditions web site, Patented Medicine Prices Review Board, La revue Prescrire, WHO Anatomical Therapeutic Chemical classification system.

Primary and secondary outcomes

Percent of new drugs evaluated by Health Canada that went through an expedited pathway between 1995 and 2016 inclusive. Kappa values comparing the review status with assessments of therapeutic value for individual drugs.

Results

Of 623 drugs approved by Health Canada between 1995 and 2016, 438 (70.3%) drugs went through the standard pathway and 185 (29.7%) an expedited pathway. Therapeutic evaluations were available for 509 drugs. Health Canada used an expedited approval pathway for 159 of the 509 drugs, whereas only 55 were judged to be therapeutically innovative. Forty-two of the 55 therapeutically innovative drugs received an expedited review and 13 received a standard review. The Kappa value for the entire period for all 509 drugs was 0.276 (95% CI 0.194 to 0.359) indicating 'fair' agreement between Health Canada's use of expedited pathways and independent evaluations of therapeutic innovation.

Conclusion

Health Canada's use of expedited approvals was stable over the entire time period. It was unable to reliably predict which drugs will offer major therapeutic gains. The findings in this study should provoke a discussion about whether Health Canada should continue to use these pathways and if so how their use can be improved.

SUBMITTER: Lexchin J

PROVIDER: S-EPMC6119438 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Health Canada's use of expedited review pathways and therapeutic innovation, 1995-2016: cross-sectional analysis.

Lexchin Joel J

BMJ open 20180830 8

<h4>Objectives</h4>This study examines the use of expedited approval pathways by Health Canada over the period 1995 to 2016 inclusive and the relationship between the use of these pathways and the therapeutic gain offered by new products.<h4>Design</h4>Cross-sectional study.<h4>Data sources</h4>Therapeutic Products Directorate, Biologics and Genetic Therapies Directorate, Notice of Compliance database, Notice of Compliance with conditions web site, Patented Medicine Prices Review Board, La revue ...[more]

PMID: 30166310

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Project description:BackgroundResearch on contraceptive behaviour changes over time in Uganda is scarce, yet it has among the highest fertility and maternal mortality rates of any country in the East African region. Understanding temporal patterns of contraceptive use for both women and men is vital in evaluating the effectiveness of family planning interventions and strategies, and identifying those with the most unmet need. Using repeated nationally representative cross-sectional samples, this study charts the changes in Uganda's population-based contraceptive use over recent years.MethodsFive Demographic and Health Survey datasets for Uganda over 21 years, from 1995 to 2016, were sourced and interrogated. Eligible participants included all women aged 15-49 years and men aged 15-54 years. Responses to questions on modern and any (modern or traditional) contraceptive use were analysed. Stratified by gender, weighted regression analyses were employed to detect change over time. The patterns associated with key demographic variables were also investigated.ResultsOverall, 50,027 women and 14,092 men were included within the study. In 2016, 30.3% of women and 39.9% of men were using any contraceptive method, a significant non-linear increase from 13.4% of women and 20.3% of men in 1995. Furthermore, 27.3% of women and 35.9% of men were using modern contraceptive methods in 2016, an increase from 7.4% of women and 10.4% of men in 1995. All considered demographic variables were significantly associated with contraceptive use for both women and men (all P<0.001); and for women, all variables differentially changed over time (all P<0.001).ConclusionThis study showed a significant increase and dynamism across key demographic variables in contraceptive uptake by both women and men. Sustained family planning programs and interventions have successfully resulted in behaviour change across the Ugandan population. However, continued efforts are needed to further reduce Uganda's relatively high fertility and associated maternal mortality rates.

Project description:BackgroundIn situations of unmet medical need or in the interests of public health, expedited approval pathways, including conditional marketing authorisation (CMA) and accelerated assessment (AA), speed up European Medicines Agency (EMA) marketing authorisation recommendations for medicinal products. CMAs are based on incomplete benefit-risk assessment data and authorisation remains conditional until regulator-imposed confirmatory postmarketing measures are fulfilled. For products undergoing AA, complete safety and efficacy data should be available, and postauthorisation measures may include only standard requirements of risk management and pharmacovigilance plans. In the pivotal trials supporting products assessed by expedited pathways, surrogate endpoints reduce drug development time compared with waiting for the intended clinical outcomes. Whether surrogate endpoints supporting products authorised through CMA and AA pathways reliably predict clinical benefits of therapy has not been studied systematically. Our objectives were to determine the extent to which surrogate endpoints are used and to assess whether their validity had been confirmed according to published hierarchies.Methods and findingsWe used European Public Assessment Reports (EPARs) to identify the primary endpoints in the pivotal trials supporting products authorised through CMA or AA pathways during January 1, 2011 to December 31, 2018. We excluded products that were vaccines, topical, reversal, or bleeding prophylactic agents or withdrawn within the study time frame. Where pivotal trials reported surrogate endpoints, we conducted PubMed searches for evidence of validity for predicting clinical outcomes. We used 2 published hierarchies to assess validity level. Surrogates with randomised controlled trials supporting the surrogate-clinical outcome relationship were rated as 'validated'. Fifty-one products met the inclusion criteria; 26 underwent CMAs, and 25 underwent AAs. Overall, 26 products were for oncology indications, 10 for infections, 8 for genetic disorders, and 7 for other systems disorders. Five products (10%), all AAs, were authorised based on pivotal trials reporting clinical outcomes, and 46 (90%) were authorised based on surrogate endpoints. No studies were identified that validated the surrogate endpoints. Among a total of 49 products with surrogate endpoints reported, most were rated according to the published hierarchies as being 'reasonably likely' (n = 30; 61%) or of having 'biological plausibility' (n = 46; 94%) to predict clinical outcomes. EPARs did not consistently explain the nature of the pivotal trial endpoints supporting authorisations, whether surrogate endpoints were validated or not, or describe the endpoints to be reported in the confirmatory postmarketing studies. Our study has limitations: we may have overlooked relevant validation studies; the findings apply to 2 expedited pathways and may not be generalisable to products authorised through the standard assessment pathway.ConclusionsThe pivotal trial evidence supporting marketing authorisations for products granted CMA or AA was based dominantly on nonvalidated surrogate endpoints. EPARs and summary product characteristic documents, including patient information leaflets, need to state consistently the nature and limitations of endpoints in pivotal trials supporting expedited authorisations so that prescribers and patients appreciate shortcomings in the evidence about actual clinical benefit. For products supported by nonvalidated surrogate endpoints, postauthorisation measures to confirm clinical benefit need to be imposed by the regulator on the marketing authorisation holders.

Project description:OBJECTIVES:We report hospitalisation trends for different age groups across the states of India and for various disease groups, compare the hospitalisation trends among the older (aged 60 years or more) and the younger (aged under 60 years) population and quantify the factors that contribute to the change in hospitalisation rates of the older population over two decades. DESIGN:Serial cross-sectional study. SETTING:Nationally representative sample, India. DATA SOURCES:Three consecutive National Sample Surveys (NSS) on healthcare utilisation in 1995-1996, 2004 and 2014. PARTICIPANTS:Six hundred and thirty-three thousand four hundred and five individuals in NSS 1995-1996, 385?055 in NSS 2004 and 335?499 in NSS 2014. METHODS:Descriptive statistics, multivariable analyses and a regression decomposition technique were used to attain the study objectives. RESULT:The annual hospitalisation rate per 1000 increased from 16.6 to 37.0 in India from 1995-1996 to 2014. The hospitalisation rate was about half in the less developed than the more developed states in 2014 (26.1 vs 48.6 per 1000). Poor people used more public than private hospitals; this differential was higher in the more developed (40.7% vs 22.9%) than the less developed (54.3% vs 40.1%) states in 2014. When compared with the younger population, the older population had a 3.6 times higher hospitalisation rate (109.9 vs 30.7) and a greater proportion of hospitalisation for non-communicable diseases (80.5% vs 56.7%) in 2014. Among the older population, hospitalisation rates were comparatively lower for females, poor and rural residents. Propensity change contributed to 86.5% of the increase in hospitalisation among the older population and compositional change contributed 9.3%. CONCLUSION:The older population in India has a much higher hospitalisation rate and has continuing greater socioeconomic differentials in hospitalisation rates. Specific policy focus on the requirements of the older population for hospital care in India is needed in light of the anticipated increase in their proportion in the population.

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Dataset Information

Health Canada's use of expedited review pathways and therapeutic innovation, 1995-2016: cross-sectional analysis.

Objectives

Design

Data sources

Primary and secondary outcomes

Results

Conclusion

Publications

Health Canada's use of expedited review pathways and therapeutic innovation, 1995-2016: cross-sectional analysis.

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