Department of Medicine, University of Toronto, Toronto, Canada.
Division of Hematology and Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.
Cancer Med. 2019 Jul;8(8):3770-3781. doi: 10.1002/cam4.2269. Epub 2019 May 27.
The soaring costs of anti-cancer drugs pose a threat to the sustainability of cancer care. The pricing strategy chosen by manufacturers can impact the costs of oral anti-cancer drugs during dose modifications, but this issue remains under-recognized in the literature. In general, with the flat pricing strategy, there is a single fixed price for each tablet regardless of dosage strength, whereas with linear pricing, the price of each tablet increases with its dose. We hypothesize that flat pricing will have increased drug costs compared to linear pricing during dose reductions since the cost remains fixed despite decreased dose requirements. This practice may have significant financial implications considering the high costs, extensive utilization, and frequent occurence of dose reductions with anti-cancer drugs. METHODS: Oral anti-cancer drugs reviewed by the pan-Canadian Oncology Drug Review program between 2011 and 2018 were identified. The cost per mg and cost per 28-day cycle were calculated for dose levels -2 to +2. The percent change in cost per mg and cost per cycle during dose modifications from the standard dose were calculated. We conducted Mann-Whitney U and Fisher-exact tests to compare the association between drug costs during dose reductions and pricing strategy.
In this study, 30 oral anti-cancer drugs for use in 41 indications were analyzed; 44% of drugs used linear pricing and 56% used flat pricing. Dose reductions increased the mean cost per mg for drugs with linear pricing by 14.7% (range: 0%-50%) at dose level -1 and 17.2% (range: 0%-50%) at dose level -2 and flat pricing by 60.8% (range: 19%-100%) at dose level -1 and 99.1% (range: 0%-300%) at dose level -2. The cost per mg was significantly increased in drugs using flat pricing compared to linear pricing when dose reduction to either level -1 (P = 0.010) or level -2 (P = 0.006) occurred. The mean cost per cycle was decreased for drugs using linear pricing by 20.9% (range: -40% to 0%) at dose level -1 and 48.7% (range: -60% to -25%) at dose level -2 and flat pricing by 0.8% (range -6% to 0%) at dose level -1 and 11.0% (range: -50% to 100%) at dose level -2. The cost per cycle was significantly decreased in drugs with linear pricing compared to flat pricing when the standard dose is reduced to either dose level -1 (P = 0.005) or dose level -2 (P = 0.026).
Overall, flat pricing had significantly greater costs compared to linear pricing during dose reductions of anti-cancer drugs. While there is a general expectation that the cost of drugs should decrease with dose reduction, drugs with flat pricing were generally found to have increased cost per mg and no change in the cost per cycle. The resultant increased spending on drug acquisition (despite purchasing lower doses) lead to financial wastage, which has significant implications on cost-effectiveness considerations and budgets. Future economic evaluations should take into consideration the hidden costs associated with dose reductions of flat priced drugs.
抗癌药物的高昂成本对癌症治疗的可持续性构成了威胁。制造商选择的定价策略会影响口服抗癌药物在剂量调整期间的成本，但这一问题在文献中仍未得到充分认识。一般来说，采用固定价格策略时，每个片剂的价格都是固定的，与剂量强度无关，而采用线性定价策略时，每个片剂的价格会随着剂量的增加而增加。我们假设，与线性定价相比，在剂量减少时，固定价格策略会导致药物成本增加，因为尽管剂量需求减少，但成本仍然固定。考虑到抗癌药物的高成本、广泛使用和频繁剂量减少，这种做法可能会产生重大的财务影响。
确定了 2011 年至 2018 年间经泛加拿大肿瘤药物审查计划审查的口服抗癌药物。计算了剂量水平 -2 至 +2 的每毫克和每 28 天周期的成本。计算了从标准剂量开始剂量减少时每毫克和每个周期成本的变化百分比。我们进行了曼-惠特尼 U 检验和 Fisher 精确检验，以比较药物成本在剂量减少期间与定价策略之间的关联。
本研究分析了 41 种适应证的 30 种口服抗癌药物；44%的药物使用线性定价，56%的药物使用固定定价。在剂量水平 -1 时，使用线性定价的药物的每毫克成本增加了 14.7%（范围：0%-50%），在剂量水平 -2 时增加了 17.2%（范围：0%-50%）；而使用固定定价的药物的每毫克成本在剂量水平 -1 时增加了 60.8%（范围：19%-100%），在剂量水平 -2 时增加了 99.1%（范围：0%-300%）。与线性定价相比，在剂量减少到任一水平（-1 或-2）时，使用固定定价的药物的每毫克成本显著增加（P=0.010）。在剂量水平 -1 时，使用线性定价的药物的每周期成本降低了 20.9%（范围：-40%至 0%），在剂量水平 -2 时降低了 48.7%（范围：-60%至-25%）；而使用固定定价的药物的每周期成本降低了 0.8%（范围：-6%至 0%），在剂量水平 -1 时降低了 11.0%（范围：-50%至 100%）。与线性定价相比，当标准剂量减少到任一剂量水平（-1 或-2）时，使用线性定价的药物的每周期成本显著降低（P=0.005）。
总体而言，与线性定价相比，在抗癌药物剂量减少时，固定定价的成本显著增加。虽然人们普遍认为药物成本应该随着剂量减少而降低，但使用固定定价的药物通常会导致每毫克成本增加，而每个周期的成本没有变化。药物采购成本的增加（尽管购买了较低剂量的药物）导致了财务浪费，这对成本效益考虑和预算有重大影响。未来的经济评估应考虑到与固定价格药物剂量减少相关的隐藏成本。
