Research Letters

The aim of the present study was to investigate increased out-of-pocket drug costs and financial burdens of achieving adherence to oral antidiabetic medications and medications for prevalent comorbidities. Concurrent adherence to medications, out-of-pocket drug costs, and financial burdens were measured among non-elderly adults with diabetes in the Medical Expenditure Panel Survey. "Financial burden" was defined as spending on health care exceeding 10% of family income. This study simulated the increased out-of-pocket drug costs and financial burdens that would result if non-adherent adults in our sample had obtained sufficient medications to be adherent. For each adult, for all therapeutic classes in which they were non-adherent, we calculated the additional days supplied required to become adherent, as well as out-of-pocket spending on these additional days supplied. Approximately one-quarter adhered to all required medications. Among non-adherent adults with employer-sponsored insurance and public insurance, the mean annual out-of-pocket drug costs of achieving adherence were US$171 and US$68, respectively, which was generally affordable. However, 35.6% of the uninsured lived in families that spent 10% or more of their income on health care. Mean simulated additional out-of-pocket drug costs of achieving adherence were US$310 for the uninsured. These additional drug costs would increase those spending 10% or more of income to 39.6% of the uninsured. Efforts to reduce the costs faced by the uninsured and insured will make adherence more affordable and, therefore, more attainable for some adults with diabetes.

Little is known about the financial burden of individuals with depressive symptoms. This study explored that burden, using data from the Survey of Health, Ageing, and Retirement in Europe. To assess the association between depressive symptoms and the individuals' financial burden for medical care and whether they forwent medical care because of costs, logistic regressions were performed that adjusted for age, gender, marital status, education, and chronic diseases. A total of 16,696 noninstitutionalized individuals aged 50-79 years were included in the study. Individuals with depressive symptoms and those without such symptoms bore a similar financial burden. However, individuals with depressive symptoms were at increased risk of forgoing care because of costs, which may worsen their health and financial situation

6605 Background: Accumulating evidence supports the clinical benefit of targeted therapies matched to cancer patients based on genomic alterations. CGP, which detects all classes of alterations (base pair substitutions, copy number, insertions/deletions, and rearrangements), can match more patients with available and investigational therapies. This study estimated anti-cancer drug costs and overall survival (OS) for matched vs. unmatched therapy. Methods: Costs were estimated for patients with complete data (N = 188/500) from a prospective, nonrandomized, phase I oncology center study of patients with diverse refractory cancers who underwent CGP and were treated with matched or unmatched therapy (PMID: 27197177). Average time to treatment failure and average OS were assessed during the observation period. Patient-specific drug and administration costs were imputed for the first regimen after CGP based on drug classes, unit costs, and times to treatment failure. Results: Patients onmatched (N = 122) vs. unmatched (N = 66) therapy had, on average, longer time on treatment (+1.5 mos), longer observed survival (+2.4 mos), and higher anti-cancer drug costs (+$38K) (all p < 0.01); 66% of increased drug costs were attributable to longer time on treatment as opposed to higher monthly drug costs. Combination therapy was used for 71% of matched and 53% of unmatched patients. Those undergoing CGP in earlier-line (1-3; N = 58) vs. later-line (4+; N = 130) therapy had numerically larger incremental increases in average times on treatment (+1.9 vs. +1.2 mos) and survival (+2.5 vs. +2.1 mos), and numerically lower incremental drug costs (+$27K vs. +$43K), with matched vs. unmatched therapy. Conclusions: For patients cared for in a phase I clinic, matched vs. unmatched therapy was associated with longer treatment durations, longer survival times, and manageable incremental costs. Despite frequent use of combination therapy, most of the increased costs of matched therapy were due to longer treatment times rather than higher monthly drug costs. Benefits of matching were numerically greater in earlier- vs. later-lines, consistent with the value of earlier-line use of CGP to guide treatment.

Introduction HIV infection has important economic, societal and financial consequences, in terms of loss of productive labour, disruption of household units and burden of treatment costs on health-care systems [1]. Approximately 25–30% of infants born to HIV-infected mothers in developing countries are infected [2,3], and approaches to reducing the rate of mother-to-child (vertical) transmission (MCT) not only include prevention of new infections in women of childbearing age, but also specific therapeutic interventions targeted at pregnant women, modification of obstetric practices, and substitution of formula (bottle) feeding for breast-feeding where feasible and affordable [3]. To date, the only approach of proven effectiveness is the administration of zidovudine therapy during pregnancy, delivery and in the neonatal period in the absence of breastfeeding, as demonstrated in the United States and France [4], and very recently with a short regimen from 36 weeks of pregnancy and during delivery in Thailand [5]. Within the next year, the results of the ongoing antiretroviral trials for prevention of MCT of HIV infection in several African countries could confirm the benefit of zidovudine in breastfeeding populations. However, reduction of the risk of MCT is only one of many demands on the health–care systems, and before decisions are taken on implementation of vertical transmission therapeutic interventions, issues relating to the implementation into public health measures need to be addressed. In this article we review economic evaluation as an approach to assist in the development of policies regarding the prevention of MCT in developing countries, using data from studies evaluating antiretroviral therapy in sub-Saharan Africa and Thailand. Principles of economic evaluation It is generally agreed that economic evaluations of MCT interventions should conform to the widely agreed practices regarding economic evaluations in general, with transparency in analysis and presentation [6–9]. The following methodological elements are applicable to the case of MCT interventions. Costs are defined as the monetary value of resources used as a result of the intervention(s) under consideration. The intervention's outcome(s) might be measured in several ways, including clinical outcome (paediatric HIV infection), monetary benefits, and subjective preferences, for example quality of life, often combined with survival to produce expected quality-adjusted life-years (QALY) gained or productivity/disability-adjusted life-years (DALY). By convention, evaluations comparing monetary costs with monetary outcomes are termed ‘cost-benefit', whereas evaluations comparing monetary costs with commensurate non-monetary outcomes are termed ‘cost-effectiveness'. As a subset of cost-effectiveness evaluations, those using subjective preferences as outcomes are termed ‘cost-utility’ analyses. Economic evaluations typically involve a relative assessment (i.e., a comparison of consequences of two or more approaches, one of which is usually either the status quo or no intervention). This requires that the outcomes of all the interventions under consideration are measured in the same units. Costs and outcomes generally have a different impact on different individuals or groups, such as the patient, the patient's household, the health-care system or society as a whole, and the frame of reference must be clearly defined and presented. It is possible that an intervention that is cost-beneficial to the public health system is not so for certain individuals. If some parameters used in the evaluation are variable rather than constant, results must be subjected to sensitivity analysis, and be interpreted as ranges of values. Costs and outcomes occurring over time must be the subject of discounting to make time-dependent values commensurate [9]. The discount rate reflects social time preference, which under perfect markets equals the opportunity cost of capital employed. The discount rate is likely to be a function of economic affluence, with people in poorer countries placing a higher premium on present consumption than those in richer countries. By implication, the appropriate discount rate for poorer countries would be higher than that for richer countries. Debate persists over whether non-monetary outcomes should be discounted at all and, if they are, whether the appropriate rate is higher or lower than, or equal to, the rate for costs [10]. However, it is essential that a sensitivity analysis of the choice of discount rate is conducted for all evaluations, and that when several interventions are being compared, common assumptions regarding the discount rate are employed. Review of evidence Available evidence relates to two studies in sub-Saharan Africa [11,12] and two in Thailand [13,14], and refers to settings where trials are currently ongoing to evaluate specific antiretroviral therapy interventions to reduce vertical transmission. The main methods, parameters and results for the economic models in these studies are summarized in Tables 1 and 2. The potential cost-effectiveness of a short-course (4 weeks at 600 mg per day prepartum) of zidovudine therapy for a hypothetical 1-year birth cohort in a developing country was estimated using a decision model [11], with assumptions made regarding the prevalence of HIV infection, the extent of breastfeeding, HIV transmission rates, costs of zidovudine therapy, testing and counselling. For the modelled cohort of 100 000 births with base-case parameters, the incidence of infant HIV infection would be reduced by 12%. The cost of the antiretroviral programme would be about US$ 20 per birth, of which 24% represents drug costs. Health-care costs of infected infants would fall by a small amount. Sensitivity analysis indicated that the programme would be cost-saving from a societal perspective if antenatal HIV prevalence was above 18%, if the cost of testing/counselling was below US$ 12 or if medical care costs for infected infants exceeded US$ 4145. However, the estimated programme costs of around US$ 20 per capita would represent a major proportion of total health-care costs in many developing countries. It was concluded [11] that it is unlikely that, in developing countries, a zidovudine intervention programme would create direct savings from the health-care system perspective, but it may prove cost-effective from a societal perspective.Table 1: Summary of methods, parameters and results of the economic models.Table 1: (continued)Table 2: Summary of clinical and efficacy parameters applied in the economic models*.The second study relevant to the African context considered three short-term regimens of combination anti–retroviral therapy (zidovudine and lamivudine), as used in the UNAIDS-sponsored trial in Africa [12], and compared these three regimens with no intervention. In regimen A, combination therapy was started at 36 weeks of pregnancy and continued until 1 week postpartum, regimen B omitted the prepartum therapy, whereas regimen C omitted both pre- and postpartum therapy. The frame of reference was the public sector medical system and the study thus considered the costs of testing and counselling and antiretroviral treatment costs in relation to expected savings in infant health-care costs. Estimates are also provided of marginal net cost per expected life-year gained, weighted for both productivity and quality of life. Basic clinical parameters were derived from the published and unpublished evidence and allowed for imperfect adherence to the regimens. The shortest and most cost-effective option was regimen C. For a cohort of 100 women with 15% HIV prevalence, net costs were estimated at US$ 3617 for regimen A, US$ 1667 for regimen B, and US$ 351 for regimen C. Regimen C had a cost of US$ 1129 per HIV infection averted and a cost of US$ 60 per DALY. Sensitivity analysis revealed that regimen C was the most sensitive to testing costs and particularly sensitive to assumptions about maternal prevalence. Cost-effectiveness declined rapidly when prevalence was below 7% or when efficacy fell below 10%. When estimated drug prices fell to low levels (e.g., < US$ 0.5 per pill), the cost-effectiveness of the more drug-intensive regimens (A and B) improved. The base-case estimate of around US$ 60 per DALY gained from the most cost-effective combination antiretroviral regimen at current drug prices compares unfavourably with other public health initiatives in most settings within the developing world, for example, immunization and treatment of other sexually transmitted diseases. However, at 20% of current drug costs, both arms B and C attain cost-effectiveness values of under US$ 50 per DALY, and a MCT control programme based on short-term anti-retroviral drug regimens might then be a sensible option, particularly in areas where more cost-effective public health interventions have already been widely adopted. The first Thai study [13], conducted before the 1997 Asian economic crisis, considered the selection of an optimal intervention strategy, given a prior government commitment to devote resources to the prevention and cure of HIV/AIDS. It argued that affordability must be a key consideration in the selection process, in that policies will only be sustainable if either governments or households (or both) are in a position to provide the programme's resource base. The study modelled 10 possible strategies, eight of which involved antiretrovirals. Two concerned themselves with MCT (formula feeding alone and zidovudine plus formula feeding), whilst eight targeted infected adults either before or after the onset of AIDS. The unit costs of treatment for adults with AIDS range from about US$ 2000 per patient-year with zidovudine monotherapy to US$ 4000 per patient-year with zidovudine plus didanosine or zalcitabine combination therapy. The unit cost of treating pregnant women following the AIDS Clinical Trials Group (ACTG) 076 [4] protocol was about US$ 500 per mother–child pair. Assuming a pricing policy that fully subsidizes antiretrovirals whilst allowing for one-third recovery for other medical services, all antiretroviral options were shown to be unaffordable within the budget of the Thai National AIDS Programme, with the exception of the two MCT programmes. The modelled subsidized pricing policy would be affordable by around 50% of the population. Simulations suggested that the effectiveness (expected QALY gain) of preventing MCT is of a similar order to that of treating adults, but their cost-effectiveness ratios are about 20 times superior than antiretroviral programmes for adults. A further Thai study [14] explored the expected cost implications assuming that the full ACTG 076 protocol [4] was to be implemented in Thailand. It concluded that implementation of the ACTG 076 protocol in Thailand would not only reduce the MCT rate but would be cost-saving overall. This finding was insensitive to the choice of discount rate (within plausible bounds). The programme would be affordable within the government's AIDS budget, again before the 1997 economic crisis, even without cost recovery from private individuals. The study by Wilkinson and colleagues in this issue [15] provides additional information regarding the affordability of zidovudine therapy to reduce vertical transmission (Tables 1 and 2). In a modelling exercise, they evaluated both the long zidovudine regimen used in the ACTG 076 trial [4] and a combination regimen used in the UNAIDS trial [12] in the context of a rural population in KwaZulu Natal, South Africa, and considered issues relating to the implementation of these antiretroviral therapy interventions in a general rural population. Cost data were combined with estimates of effectiveness to calculation the cost per infection prevented; the cost per potential year of life saved was calculated using a life expectancy of 63 years. They concluded by saying that providing short-course combination therapy of zidovudine and lamivudine may be cost-effective, but questioned whether it would be a realistic public health intervention. The cost of this combination therapy is relatively high despite its short antepartum duration due to the need for two-drug therapy for both mother and child, and the recently demonstrated efficacy of short-course zidovudine monotherapy [5], with a reduction in the cost of zidovudine [12], would make this a more realistic option. Sensitivity of estimates to parameter variation To understand the implications of parameter variation for the MCT evaluation results, a simplified model of antiretroviral therapy in developing countries was constructed, which included the essential features of the studies reviewed above, and two carried out in the United States [16,17]. This was part of a consensus meeting held in June 1997, and full details of the model can be found in the report of the workshop [18]. Intervention with antiretroviral therapy necessitates screening of pregnant women, counselling and other additional antenatal care and the administration of the drug regimen. Although test sensitivity and specificity were assumed to be 100%, treatment compliance and adherence rate to the drug regimen were not. This means that a proportion of pregnant women will not be tested, or not treated adequately, and their infants will thus continue to be at high risk of acquiring HIV infection. The modelling exercise showed that the values of the parameters associated with decreased cost–benefit were high costs for screening, counselling, antenatal care and drugs, low efficacy, low costs for paediatric treatment and productivity losses, low prevalence of HIV infection in the antenatal population, and low compliance rates [18]. Movements of one or more of these parameter values in the opposite direction would make the intervention more cost–beneficial. The model also allows evaluation from the health-care system perspective, and, assuming positive efficacy and positive productivity losses, the net gain to society as a result of the intervention will always exceed that of the health-care system for any given set of parameter values. The cost–benefit model can be reinterpreted in a cost-effectiveness framework, and the relevant parameter movements noted above to decrease net benefits in the cost–benefit approach also make the intervention appear less cost-effective. In addition, the parameter that would make the intervention less rather than more cost-effective is a lower differential in discounted outcome between infected and non-infected infants. However, given the possibility of compensating effects, the reliability of parameter estimates used in these cost–benefit and cost-effectiveness exercises needs to be considered. Reliability of parameter estimates Model building to evaluate an as yet unimplemented intervention generally entails both measurement (when a relevant activity is currently in place) and assumption (when an activity is not yet in place), where the former are considered to be more reliable than the latter. A randomized controlled trial provides more convincing evidence and more precise estimates of the effect of an intervention than any other study method [19], and replication of the first trial improves confidence in reliability of the estimates [4,5]. However, although randomized controlled trials may offer the best prospect of yielding reliable estimates of clinical effect, they may be less reliable as broader indicators of how an intervention would perform in everyday practice. This is especially true for economic considerations. For example, trial participants are volunteers and clinical efficacy in terms of the number of subjects enrolled gives no indication about likely compliance rates in a general population. Furthermore, clinical trials are generally conducted within a supportive infrastructure. Resource usage in such a setting might not be typical of resource usage when the intervention is introduced across a health-care system more generally. The reported drug cost varied across studies [11,12,14,17], which reflects either the world price or the purchase price negotiated at the time of analysis. There was a more than fourfold variation in counselling and testing costs in the two African studies using evidence from Zambia [12] and Uganda [11]. This difference partly reflects the costs of labour and capital involved in the procedures. The estimate for United States costs is around US$ 100 [16]. Similarly, base estimates of mean discounted lifetime paediatric HIV treatment costs range from US$ 118 [12] and US$ 396 [11] for African settings, through approximately US$ 5000 for Thailand [14], to US$ 98 915 [17] and US$ 161 137 [16] for the United States. The conventional method for estimating the value of productivity losses is to assume that premature mortality has prevented the individual concerned from generating mean per capita gross domestic product (GDP), or some other macroeconomic aggregate, such as national income. In developing countries generally, GDP figures are considered to be less reliable, owing to measurement error and the large volume of activity generated by non-market production. Using the GDP figures specifically for the present purpose makes the strong assumption that production resulting from the avoidance of HIV infection can be represented as a mean contribution to output. This would clearly be misleading if infants concerned were born in, for example, regions where subsistence agriculture predominates or in urban areas of high unemployment. Generally, when ranking these costs on a per intervention basis, treatment costs savings and productivity losses avoided greatly exceed unit testing, counselling and drug costs. The margin between these two cost classes increases as the level of development of the country concerned increases. This leads to the general conclusion that the likelihood of an antiretroviral intervention to be shown to be cost–beneficial increases with the level of development of the country, considering only the cost variable and assuming that other factors remain unchanged. Despite the variety of settings for which MCT intervention models have been constructed, their assumed effectiveness parameters are based on the results of a single trial [4] conducted in the United States and France on mildly symptomatic women with no prior antiretroviral treatment. Although little information is available on adherence to the drug regimen, our descriptive model demonstrated the sensitivity of cost-effectiveness and cost–benefit results to compliance effects. Lower compliance reduces the intervention's effectiveness of MCT risk reduction. A study of zidovudine use among women in the United States suggests that diverse attitudinal and perceptual barriers to the use of zidovudine amongst HIV-infected women exist and that these may be strongest among minority women, particularly African Americans [20]. This may also be the case in many African countries, where fear of stigmatization is high. Completeness of the models Models are designed to answer clearly specified questions, and are constructed in order to make a complex process comprehensible. However, the assumptions used in the construction of these models should not be overlooked, especially when we consider using the results of a model as a criterion for effecting policy changes. Below we note a number of issues, explicitly absent from the economic models thus far considered, which a policymaker might consider relevant. Reducing the risk of MCT is likely to increase the number of orphans in society. Although in many countries the extended family system has been able to accommodate these children, the impact on the household economy is unknown. As HIV/AIDS deaths increase over time, more reliance may have to be placed on the government. If this factor was to be included in the evaluation models, the costs of care of orphans would offset to some degree the treatment cost saved by less HIV infection amongst infants. In addition, it is possible that the employment circumstances of orphans in any particular country would differ from that of the average individual; it is believed, for example, that orphans and children in one-parent families typically receive less education than children in two-parent families [1]. A relative lack of education would make such individuals less competitive in the labour market, other things remaining equal. Assuming we accept this proposition, then the estimates of productivity losses avoided by preventing the birth of an HIV-infected child, which are based on mean contribution to GDP, are likely to be overestimates. Assuming that antiretroviral therapy is adopted and proves acceptable to women, we could anticipate a change in behaviour with respect to decisions about reproduction that could impact on overall population growth. Reducing MCT transmission increases the probability of producing an uninfected child. This may result in either higher levels of reproduction (if families value higher numbers of healthy children) or lower levels (if families aim to achieve a given family size). Economic intuition supports either possibility and thus the reaction cannot be predicted reliably without further evidence. In the models discussed thus far, the health-care system frame of reference has not been disaggregated into public and private contributions. In policy terms, such a disaggregation may be significant, in view of the importance currently attached to user charges and cost recovery in the health-care systems of developing countries. Although there is a strong case in favour of cost recovery in health care generally, there are also important counter-arguments in specific cases, such as the administrative costs of operating charges, equity considerations and the likely disincentive effects to service use generated for households subject to charges [21]. It is quite possible, for example, for cost recovery to transfer a sufficient part of the public funding burden to households such that the practical effectiveness of the new intervention is nullified by poor uptake. In the MCT case, we do not yet possess information regarding household's price and income elasticity of demand with respect to risk-reduction services. Comparability and affordability Economic evaluation as a decision-making tool facilitates the ranking of alternatives: for example, intervention A is cost-saving relative to the status quo, or intervention A is more cost-effective than intervention B. With respect to MCT, evaluations in developing countries have generally concerned antiretroviral treatments, although other risk-reduction options are recognized [3,22]. To date, however, of these of MCT reduction have been proven to be of cost-effectiveness within MCT MCT policies are part of a more general public health programme at the of women and children and their cost-effectiveness should be compared with other public health programmes might include and and to the around of all the health of the under in developing countries can be by interventions less than US$ 100 per DALY saved The one study that has cost-effectiveness estimates [12] suggested that the cost-effectiveness of antiretroviral therapy could be below this but the reliability of this estimate for antiretroviral therapy would be by the of further evidence. However, there may be other paediatric interventions, such as prevention and treatment of which offer value for than antiretroviral therapy, and their could be more cost-effective than the of maternal antiretroviral therapy to be considered before implementation of interventions to reduce vertical evaluations of MCT interventions, either in randomized controlled trials or in should include economic evaluation to whether the if found to be can or should be implemented as a public health economic evaluations should be and include a sensitivity analysis of the most important to effectiveness and costs. However, in addition, the issue of affordability should also be and outcome measures and of both to comparison with other interventions and to potential between the of of decision should be employed. information regarding the cost-effectiveness of antiretroviral therapy in reducing vertical transmission a degree of particularly until the Thai results available the efficacy of short-course treatment was [5]. is and policy decisions regarding anti-retroviral interventions should be based on of the results of trials currently in In the cost-effectiveness of antiretroviral therapy in countries is more sensitive to the drug price than it is in or However, within the range of antiretroviral interventions for HIV treatment in general, it is likely that MCT prevention will prove both more cost-effective and affordable than and will part of the HIV in many developing countries. relating to affordability and remain to be addressed. The for the and the workshop for their general and their on the

Objective:Compare direct and indirect costs of oxymorphone extended-release (‘oxymorphone’) and oxycodone controlled-release (‘oxycodone’) users.Methods:Patients, aged 18+, with ≥1 claim for oxymorphone/oxycodone, Q2:2006–Q4:2009, were selected from a de-identified private payer claims database and observed from the first such claim (‘index date’) until the earliest of: use of comparator drug; end of continuous eligibility; 12 months (‘study period’). Patients with claims for any formulation of the comparator drug during the first 30 days of the study period were excluded. Direct (medical and drug) costs paid by private insurers were reported for patients aged 18–64 (n = 8354) and 65+(n = 3515), as well as sub-sets without cancer (n = 7090 and n = 2444, respectively). Indirect costs (medically-related absenteeism and disability) were reported for all employees, aged 18–64 (n = 1313), and employees without cancer (n = 1146). Multivariate models were used to estimate risk-adjusted costs controlling for patient characteristics.Results:Oxymorphone users, aged 18–64, had lower drug costs ($693 vs $763, p = 0.0035) and similar medical costs ($1875 vs $1976, p = 0.3570) per patient-month compared with oxycodone users (mean follow-up 236 and 280 days, respectively). Indirect costs were not different ($662 vs $670, p = 0.9370). Oxymorphone users, aged 65+, had similar Medicare supplemental drug costs ($533 vs $588, p = 0.0840) and lower medical costs ($459 vs $747, p < 0.0001). Results were comparable for subsets without cancer.Limitations:Patients with concomitant use of oxymorphone and oxycodone were excluded.Conclusions:Oxymorphone users incur lower risk-adjusted costs in several cost categories, compared with oxycodone users, and no higher costs in any of the examined categories.

Can Patients Afford to Be Adherent to Expensive Oral Cancer Drugs?: Unintended Consequences of Pharmaceutical Development.

An Inside View: AGA Advocacy Priorities

PSY132 - ECONOMIC CRISIS AND THE EFFECT ON PHARMACOECONOMICS IN A REGIONAL GENERAL HOSPITAL

Dear Editor, The costs of antipsychotic drugs (APDs) used in the treatment of mental disorders with psychosis are mentioned in treatment guidelines (APA 2021, NICE 2014). While the American Psychiatric Association guideline states that every specialist should make decisions according to the rules and conditions of their country and their region, the National Institute of Health and Clinical Excellence guideline emphasizes that drug costs must be taken into consideration in the treatment process. Classical or first-generation antipsychotic drugs (FAPDs) are relatively cheaper in terms of sales prices compared to atypical or second-generation antipsychotic drugs (SAPDs) with a slightly different effect mechanism. The price difference between the two drug groups can be so large that sometimes it may be necessary to consider whether the cost of a second-generation drug is worth its benefit. While deciding on the use of first-generation or second-generation drugs, a multifaceted assessment should be made, such as the patient's level of compliance with the treatment, the possibility of occurrence of side effects, the possible effects of these side effects on body health and treatment compliance, and whether or not the costs are covered. The most important criterion that determines the choice of medication for psychiatrists is of course the multi-dimensional benefit/harm ratio that the drug used will reveal in the long term. We think that in our country, which, in terms of economic indicators is not in a strong position as an importer of pharmaceutical raw materials from abroad, APDs' cost calculation should be considered because drug costs constitute an important part of the direct treatment costs of psychotic disorders in developing countries such as Turkey (Yıldız and Cerit 2006). We calculated the unit (mg) price based on the box prices of the APDs in use in 2020, thinking that it might work when calculating the cost of the illness using APDs as the main component of the treatment and calculated the annual average drug costs with the daily average dosage. Although the daily treatment dose varies with the stage of the illness and the individual characteristics of the patient, the average doses recommended for maintenance treatment were used here (Öztürk and Ulusahin 2018). The daily and annual cost calculations based on the assumption that the average maintenance treatment dose was used with the unit price obtained from (Drug Prices 2020) the drugs in the Turkish pharmaceutical market in September 2020 are shown in Table 1. A similar study was done in 2005 (Yıldız 2005). The purpose of this article is to redetermine the average costs of APDs in the Turkish pharmaceutical market every 15 years and to bring them to the attention of experts in terms of cost-effectiveness studies. When the costs in 2005 are examined, it is seen that the annual costs of the FAPDs were around 450 TRY, and the annual cost of oral preparations of SAPDs was 2,500 TRY (5 times the first generation). In 2005, there was only one depot of SAPD (risperidon consta) that allowed intramuscular (IM) administration, and its average annual cost was 5,400 TRY, 3 times more than the tablet form (1,700 TRY). In 2005, when the price of risperidone consta, which was the first second-generation depot APD, were compared with the prices of the first-generation depot drugs (fluphenazine = 380 TRY, flupentixol = 876 TRY, zuclopentixol = 730 TRY), the cost difference was 6-14 times. This almost-10-fold difference between the cost of the first and second generation APDs was remarkable. It is seen that this difference (risperidone consta = 10,807 TRY, fluphenazine = 916 TRY, flupentixol = 1,007 TRY, zuclopenthixol = 2,372 TRY, and haloperidol deconate 237 TRY) did not change in 2020. In 2020, the average RETHINKING THE COST OF ANTIPSYCHOTIC TREATMENT: THE AVERAGE COST OF THE DRUGS USED IN TURKEY IN 2020 2 Türk Psikiyatri Dergisi 2 Turkish Journal of Psychiatry Letter to the Editor 146 147 annual cost of oral use preparations of FAPDs is 925 TRY, while the average annual cost of oral forms of SAPDs is 2,580 TRY. The 5-fold difference observed in 2005 between the first and second-generation ones of the oral APDs decreased to 2.5 times in 2020. It is clear that while the difference between the cost of oral use of first- and second-generation drugs was halved in 2020, the difference between the costs of depot preparations applied with IM did not change. In 2005, the average dollar rate was 1.34 TRY, and in 2020 it was 7.02 TRY (Republic of Turkey Central Bank Exchange Rates, 2021). It is understood that the 5-fold increase in dollar exchange rate is not reflected in all drug prices in the same way. For example, there was a 3 to 4-fold increase in the prices of haloperidol, chlorpromazine, fluphenazine, trifluperazine and zuclopenthixol, while a less than two-fold increase in pimozide, flupenthixol, sulpiride, amisulpride and quetiapine and a decrease in the prices of clozapine, olanzapine, ziprasidone and risperidone in the tablet form. There is also a two-fold increase in the price of risperidone consta. The fluctuations in drug prices in 2005 and 2020 are shown in Table 2 in 500, 1,000, 2,000, 3,000 and 5,000 TRY brackets. It is noteworthy that while some drugs have moved into an upper price bracket in terms of annual costs, some have fallen into a lower price bracket. The prices of the second generation long-acting (depot) antipsycotic drugs (LA-APDs), which were not available in the Turkish pharmaceutical market in 2005, are quite high compared to others. In 2020, the annual cost of all of them, including risperidone consta, is over 10 thousand TRY. It is understood that the underlying reason for such price increase is the fact that the drug is wanted/sought after/new/marketed rather than the dollar exchange rate. For example, while there was a certain increase in the price of FAPDs, the increase in the price of some of the SAPDs (sulpiride, amisulpride, quetiapine tablet) was low, while the price of some others (clozapine, olanzapine, ziprasidone, risperidone tablet) decreased. It should also be taken into account that the effect of generic drugs entering the market during this period may have had an impact on price changes. It is noteworthy that while the annual cost of risperidone consta was approximately 3 times higher than the tablet form (5,400 TRY versus 1,700 TRY) in 2005, this difference reached 14 folds (10,807 TRY versus 742 TRY) in 2020. In 2005, the difference between the lowest daily cost (0.07 TRY) and the highest daily cost (14.80 TRY) was 211 times (Yıldız 2005), this difference had receded to 111 times (0.35 TRY versus 38.72 TRY) in 2020. Still a huge difference, isn't it? Table 1. Current Forms, Box Prices, Daily and Annual Costs in For Maintenance Treatment of Antipsychotic Drugs Available in the Pharmaceutical Market in September 2020 in Turkey No Generic name Trade name Dosage forms (mg) BV Price# TRY/Mg ADD Cost/d Cost/y 2005** 1 Haloperidol Norodol 5, 10, 20 tb 5/50 17.57 0.070 5 0.35 127 26 5, 10 amp 5/5 5.35 0.214 5 1.07 390 - 50, 150 LAI 50/1 9.80 0.196 1/15* 0.65 237 - 2 Chlorpromazine Largactil 25,100 tb 100/30 17.92 0.006 300 1.79 653 197 3 Fluphenazine Prolixin 25 LAI 25/1 17.57 0.703 1/7* 2.51 916 380 4 Trifluoperazine Stilizan 1, 2, 5 drj; 1 amp 5/30 14.52 0.096 10 0.97 354 91 5 Pimozide Nörofren 2 tb 2/30 19.33 0.322 4 1.29 470 365 6 Flupenthixol Fluanxol 3 drj 3/50 65.75 0.438 6 2.63 960 526 20 LAI 20/1 19.33 0.966 1/7* 2.76 1,007 876 7 Zuklopenthixol Clopixol 2, 10, 25 tb 2/50 38.65 0.386 20 7.72 2,817 701 200 LAI, 50 acu 200/1 45.55 0.227 1/7* 6.50 2,372 730 8 Sulpirid Dogmatil 200 tb 200/24 23.15 0.005 600 3.00 1,095 876 9 Amisulpirid Solian 200 tb 200/60 146.92 0.012 600 7.20 2,628 2,387 10 Quetiapine Seroquel 25, 50, 100, 200, 300, 400 tb 300/30 137.17 0.015 600 9.00 3,285 2,628 11 Clozapine Leponex 25, 100 tb 100/50 32.56 0.006 400 2.40 876 1,898 12 Olanzapine Zyprexa 5, 10, 20 tb 10/28 152.96 0.546 10 5.46 1,992 2,606 13 Ziprasidone Zeldox 20, 40, 60, 80 tb 60/56 189.89 0.056 120 6.72 2,452 3,541 14 Sertindole Serdolect 4, 12, 16, 20 tb 16/28 453.53 1.012 16 16.19 5,909 - 15 Risperidone Risperdal 1, 2, 3, 4 tb; 1 sol 2/20 20.34 0.508 4 2.03 741 1,719 Ris. Consta 25, 37.5, 50 LAI 37.5/1 444.17 11.840 1/15* 29.61 10,807 5,402 16 Paliperidone Invega 3, 6, 9 tb 6/28 213.15 1.268 6 7.61 2,777 - Xeplion 50, 75, 100, 150 LAI 100/1 1161.56 11.615 1/30* 38.72 14,132 - Trevicta 175, 263, 350, 525 LAI 350/1 3426.95 9.788 1/90* 38.08 13,899 - 17 Aripiprazole Abilify 5, 10, 15, 20 tb; 1 sol 20/28 113.25 0.404 20 8.08 2,949 - Abilify Main. 400 LAI 400/1 971.17 2.420 1/30* 32.37 11,815 - BV: Baseline value (in mg of the form and the number in the box), Price#: Box price of the base value in TRY, TRY/mg: Value per milligram in Turkish Lira, ADD: Average daily dose, Cost/d: Daily cost in TRY, Cost/y: Annual cost in TRY, mg: Milligram, tb: Tablet, drj: Dragee, amp: Ampoule, LAI: Long-acting injectable, acu: Acuphase, d: Day, TRY: Turkish Lira, *LAI per 7,15,30 or 90 days, **Annual cost in TRY in 2005. 148 Received: 14.01.2021, Accepted: 31.03.2021, Available Online Date: 07.01.2022 1Prof., 2Res. Assis., Kocaeli University School of Medicine, Department of Psychiatry, Kocaeli, Turkey. e-mail: myildiz60@yahoo.com https://doi.org/10.5080/u26315 The difference in 2005 between oral FAPDs prices and SAPDs prices seems to have halved in 2020. In 2020, the average daily treatment cost of oral drugs, whether for the first generation or the second generation, is 3 TRY (approximately the same for FAPDs applied with IM), while the daily cost of LA-SAPDs is around 33 TRY. It is seen that the difference between costs is approximately 11 times. This difference increases to 50 times for haloperidol deconate. From here, the following judgment can be made: in order for LA-SAPDs to be preferred, they must be at a value that will constitute at least 11 times

Financial Burden Among Patients With Lung Cancer in a Publically Funded Health Care System

Primary central nervous system (CNS) tumors significantly affect individuals globally, with patients in Ontario, Canada, often bearing financial burdens for treatments such as oral chemotherapy due to insufficient coverage, resulting in complex insurance processes or out-of-pocket payments. However, limited understanding exists regarding other direct and indirect financial implications of their diagnosis. This study examines the financial strains, unmet needs, and overarching challenges encountered by Ontario's brain tumor patients, utilizing GoFundMe posts as a unique data source to explore additional financial costs linked to CNS tumor diagnoses in the region. A qualitative descriptive design employing thematic analysis analyzed GoFundMe posts supporting CNS tumor patients in Ontario from 2014 to 2021. A search strategy targeted posts featuring primary CNS tumor keywords, with NVivo 10 software facilitating post organization and coding. Focused on Ontario, the study yielded a final dataset of 154 posts from an initial pool of 9025, revealing further financial strain due to income loss among patients and caregivers. Posts highlighted various concerns: (1) navigating the complexities of accessing support services, (2) worries about family's long-term financial and overall well-being, (3) insufficient public awareness about the financial and emotional burden on those affected, and (4) seeking emotional support, hope, and encouragement from the community. These GoFundMe posts highlight a connection between financial burden, emotional distress, and the need for improved access to financial and emotional support services. The results emphasize distinct financial challenges faced by CNS tumor patients within Ontario's healthcare system.

101 Background: Advanced/metastatic GC and GEJC is associated with poor survival outcomes. Systemic treatment options are limited in patients having had at least two lines of chemotherapy. Immune checkpoint inhibitors (ICIs) appear to be a promising therapeutic option in these patients. The role of predictive biomarkers to response to ICIs remains to be fully elucidated. This may ultimately inform the utility and thus potentially the drug cost incurred by ICIs. The ATTRACTION-2 phase III study using N in heavily pretreated advanced GC and GEJC patients improved outcomes. The use of ICIs has an anticipated budgetary impact on health care systems within the context of this potentially funded utilization of N. Methods: An estimation of the N drug cost alone for advanced de novo and relapsed cases diagnosed in 2017 and subsequently treated in the third line in Canada was undertaken. A cost estimate for N treatment in earlier lines was also evaluated. N cost per patient was calculated based on treatment indication, duration of treatment, standard dose/schedule. The analysis was performed in Canadian dollars ($) and assumed complete drug delivery and uncomplicated cycles. The cost of N was obtained from the pan Canadian Oncology Drug Review (PCODR) cost for N in lung cancer. The number of target patients and N utilization was derived from constructed schema to give a budget impact estimate. Results: Estimated N cost per treated patient is $15,770. The N drug cost in the third line setting is estimated at $5.9 million (M) for GC and $2.4M for GEJC, total $8.4M (IQR $3.9M-$18.7M). For first line and second line N in eligible pts respectively: potential drug cost is $23.7M, $11.8M for GC and $9.7M, $4.9M for GEJC. A sensitivity analysis was performed. Conclusions: ICIs potentially add a drug cost burden to the publically funded Canadian healthcare system. As biomarkers predictive of response evolve and patients are treated accordingly, the drug cost burden may lessen. Potential earlier line use and a longer duration of therapy will add to the estimated budgetary impact.

Hemophilia B is a rare X-chromosome linked hereditary bleeding disorder. Patients require lifelong treatment and it is costly, but there is a lack of research in China on the treatment and burden for this group. Our aim was to review the actual treatment pattern of hemophilia B patients in China, and describe the financial burden and other disease burden from the patient's perspective. Using data collected by the Beijing Hemophilia Home Care Center, descriptive statistics were made on the sociodemographic characteristics and treatment of patients. The annual drug costs were calculated according to the actual factor dosage and price. During the study period, 29.9% of the patients only received on-demand treatment, while the rest of the patients received varying numbers of prophylaxis treatment. The total cost of clotting factors for 341 patients in one year was 16.0 million CNY ($2.5 million), with 46990.8 CNY ($7283.7) per patient. The drug cost of prophylaxis was significantly higher than that of on-demand treatment. The amount of prothrombin complex concentrates used by patients was the largest, more than 5 times of recombinant coagulation factor IX. Based on the average annual wage and average working time of Chinese employees in 2021, the average annual wage loss of HB patients reached 31544.2 CNY ($4889.4). The results of the questionnaire showed that 77.1% and 65.3% of patients had chronic pain and acute pain of different frequencies. The level of prophylaxis for Chinese patients is low; safer and more effective recombinant drugs are not widely available. Patients also face a high burden of drug costs, as well as indirect costs that cannot be underestimated. Therefore, continued efforts are needed to improve the quality of life of patients by reducing their financial burden and promote standardized treatment.

Public prescription drug plans vary markedly across Canada. To address perceived inequities in coverage across provinces, the February 2003 First Ministers' Accord on Health Care Renewal committed to ensuring that all Canadians have reasonable access to catastrophic drug coverage. A national standard for "reasonable" catastrophic coverage has yet to be formally defined. To compare the private financial burdens from prescription drugs that Canadian households would face if each of the current provincial pharmacare models were adopted as the national standard. Through simulation modelling, we computed household private financial burden by applying the cost-sharing rules from provincial drug plans to a nationally representative set of 4,860 household types differing in size, age composition, income and drug expense levels. The proportions of households that would face private out-of-pocket payments exceeding critical, or catastrophic, percentages of household income were calculated. Private financial burden due to prescription drug costs varies considerably across provincial pharmacare models. Comprehensive, tax-financed pharmacare models that limit out-of-pocket expenditures to a given percentage of income, such as those found in British Columbia, Saskatchewan, Manitoba and Ontario, provide the greatest protection against catastrophic prescription drug costs. There appears, however, to be no "gold standard" for an acceptable financial burden to be borne by patients.

PCN316 A Systematic Review of the Socioeconomic Impact of Cancer on Patients and Families: Are Differences Among Countries Being Effectively Captured and Addressed?