Response to "Canadians Need Improved Access to Drugs for Rare Diseases, Not More Denial".

The comments provided by Rawson and Adams (2023) miss the mark of our articles (Sirrs et al. 2023a, 2023b). We agree that the patient perspective is critical and that patients with "rare diseases have a right to healthcare and have huge unmet needs …" (p. 7). However, we challenge Rawson and Adams' (2023) thesis that keeping drug prices higher in Canada than in most other countries would solve the problem of access to therapies for rare diseases that have no available treatment.

Expensive Drugs for Rare Diseases in Canada: What Value and at What Cost?

There has been explosive growth in the market for expensive drugs for rare diseases (EDRDs). Traditional standards of evidence are not achievable for rare diseases, so lower standards are applied. The price of these drugs is extremely high. This combination of lower standards and higher prices make EDRDs attractive to manufacturers. Legislation designed to incentivize drug development for rare diseases contains loopholes that drive prices up worldwide. Canada compounds those problems with a complex network of agencies that impede communication between those providing market authorization and those purchasing drugs. Drug pricing is not related to metrics like investment or value, but rather willingness to pay. Without high-quality evidence to assess value, we inadvertently prioritize patients with rare diseases over those with common diseases, creating conflict among ethical principles such as social utility, justice and the rule of rescue. Lack of transparency over what is being funded and for whom makes it hard to mitigate challenges through effective policy development. We review the evidentiary, economic and ethical issues around EDRDs and ways to move forward, including enhanced transparency and the development of high-quality evidence to ensure that we do not pay for drugs that do not work.

Expensive Drugs for Rare Diseases in Canada: Time for Action Everywhere and by Everyone.

Expensive drugs for rare diseases pose unique economic, evidentiary and ethical challenges, and these will continue to escalate unless steps are taken urgently to address these challenges. We propose concrete actions that all stakeholders (federal and provincial/territorial governments, patients, healthcare providers, the public and drug manufacturers) could take now as a first step toward enhancing sustainability in the use of innovative (albeit expensive) therapies within our publicly funded healthcare system.

Anti-TNF Re-induction Is as Effective, Simpler, and Cheaper Compared With Dose Interval Shortening for Secondary Loss of Response in Crohn's Disease.

BACKGROUND AND AIMS: The optimal duration of dose-intensified therapy following secondary loss of response [LOR] to anti-tumour necrosis factor [TNF] therapy remains unclear. Anti-TNF re-induction involves a finite period of intensified therapy and may be a cost-effective means of re-capturing response. This study aimed to compare the efficacy, durability, and cost of anti-TNF re-induction and dose interval shortening [DIS] for secondary LOR in Crohn's disease [CD]. METHODS: This was a retrospective observational study in CD patients who developed secondary LOR to maintenance anti-TNF therapy, requiring subsequent re-induction and/or DIS. The primary outcome was treatment failure within 12 months. Secondary outcomes included factors associated with time to failure, disease activity, and incremental anti-TNF costs. RESULTS: Of 423 patients with CD on anti-TNF therapy, 80 [19%] developed secondary LOR, with 33 and 55 patients undergoing subsequent anti-TNF re-induction and DIS, respectively. There was no significant difference in the incidence of treatment failure at 12 months following re-induction and DIS, respectively [p = 0.27]. Factors predictive of a longer time to failure included a higher baseline serum albumin, male sex, and thiopurine co-therapy [each p < 0.05], whereas higher baseline faecal calprotectin was associated with shorter time to failure. There was no significant difference in clinical remission or objective disease activity across both groups. The median incremental cost of re-induction and DIS was AUD 4 838 and AUD 13 190, respectively. CONCLUSIONS: In patients with CD who develop secondary LOR, re-induction may represent an effective and less expensive first-line strategy, reserving dose intensification strategies such as DIS for non-responders.

Rates of breast cancer surgery in Canada from 2007/08 to 2009/10: retrospective cohort study.

BACKGROUND: Surgery is a common and important component of breast cancer treatment. We assessed the rates of breast cancer surgery across Canada from 2007/08 to 2009/10. METHODS: We used hospital and day surgery data from the Canadian Institute for Health Information to assemble a cohort of women who had undergone breast cancer surgery. We identified the index surgical procedure and subsequent surgical procedures performed within 1 year for each woman included in the analysis. We calculated the crude mastectomy rate for each province, and we calculated the adjusted mastectomy rate for select jurisdictions using a logistic regression model fitted using age, neighbourhood income quintile and travel time. RESULTS: In total, 57 840 women underwent breast cancer surgery during the study period. Among women with unilateral invasive breast cancer, the crude mastectomy rate was 39%. Adjusted rates for mastectomy varied widely by province (26%-69%). The rate of re-excision within 1 year for women who had breast-conserving surgery as their index procedure was 23% and varied by province in terms of frequency and type (mastectomy or repeat breast-conserving surgery). Among women who underwent mastectomy for unilateral invasive breast cancer, 6% also underwent contralateral prophylactic mastectomy, and 7% had immediate breast reconstruction following surgery. Of mastectomy procedures, 20% were performed as day surgery; for breast-conserving surgery, 70% were performed as day surgery. INTERPRETATION: There is substantial interprovincial variation in surgical care for breast cancer in Canada. Further research is needed to better understand such variation, and continued monitoring should be the focus of quality initiatives.

Transnational comparison: A retrospective study on e-health in sparsely populated areas of the northern periphery.

Healthcare delivery in the northern periphery of Europe is challenged by dispersed populations, geographical complexities (including mountainous terrain and inhabited islands), ageing populations, and rising patient expectations. It is challenged further by variations in transport networks and information communication technology infrastructure. This article provides an overview of e-health development across the northern periphery areas of four northern European countries (Finland, Sweden, Norway, and Scotland) by summarizing the outcomes of a mixed methods e-health mapping exercise and subsequently identifying service needs and gaps. A total of 148 applications, with a range of applied e-health solutions, were identified and the findings have promoted the sharing and transfer of e-health innovation across the four countries. The supporting telecommunications infrastructure and development of innovative telemedicine appear slower in sparsely populated areas of Scotland in comparison to its northern peripheral counterparts. All four countries have, however, demonstrated a clear commitment to the development of e-health within their remote and rural regions.

Estimating the number of coronary artery bypass graft and percutaneous coronary intervention procedures in Canada: a comparison of cardiac registry and Canadian Institute for Health Information data sources.

BACKGROUND: Provincial cardiac registries and the Canadian Institute for Health Information (CIHI) pan-Canadian administrative databases are invaluable tools for understanding Canadian cardiovascular health and health care. Both sources are used to enumerate cardiovascular procedures performed in Canada. OBJECTIVE: To examine the level of agreement between provincial cardiac registry data and CIHI data regarding procedural counts for coronary artery bypass grafts (CABGs) and percutaneous coronary interventions (PCIs). METHODS: CIHI staff obtained CABG and PCI counts from seven provinces that, in 2004, performed these procedures and had a cardiac registry (ie, British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Newfoundland and Labrador). Structured mail questionnaires, and e-mail and telephone follow-ups elicited information from a designated registry respondent. The CIHI derived its counts of CABG and PCI procedures by applying the geographical boundaries, procedural definitions and analytical case criteria used by the cardiac registries to CIHI inpatient and day procedure databases. Steps were taken to reduce double-counting procedures when combining results from the two CIHI databases. Two measures were calculated: the absolute difference between registry and CIHI estimates, and the per cent agreement between estimates from the two sources. RESULTS: All seven cardiac registries identified as eligible for the study participated. Agreement was high between the two sources for CABG (98.8%). For PCI, the level of agreement was high (97.9%) when CIHI sources were supplemented with day procedure data from Alberta. CONCLUSIONS: The high level of agreement between cardiac registry and CIHI administrative data should increase confidence in estimates of CABG and PCI counts derived from these sources.