Heterogeneity in learning processes and the evolution of dynamic managerial capabilities as a response of emergence of biosimilar market: evidence from the Indian pharmaceutical industry

ABSTRACT

This paper examines heterogeneity in the response of Indian firms to the emergence of a new segment in the pharmaceutical generics market – biosimilars. The necessary diversity of the knowledge base and regulatory requirements underlying biosmilar products have created significant technological capability and market access challenges for Indian firms. This is but the latest development which adds to an existing catalogue of challenges including the decline of the traditional generics markets, regulatory hurdles in advanced country markets and failures in managing new drug development. Using case studies of three Indian firms we show that dynamic managerial capability is a key driver of heterogeneity in learning processes involved in acquisition of technological capabilities for biosimilars and market access strategies. It further highlights the important role of pre-existing capabilities in enabling and constraining the development of new biosimilar capabilities.     

Imitation and innovation new biologics,biosimilars and biobetters

ABSTRACT

Biopharmaceutical drugs are the future of the pharmaceutical industry. The United States is the world leader in the development of new biopharmaceutical products. These original new drugs, numbering close to 200, are now losing patent protection and imitators from several countries are entering the markets of comparable drugs, called biosimilars. Some companies are improving the original product, and these drugs are called biobetters. Even among the producers of biosimilars one finds different strategies, and these are linked to different government regulations concerning the approval of these products. Some biosimilar companies are aiming at developed-country markets (North America, the European Union and Japan), while other producers are targeting emerging, less-regulated markets. This introduction will present the dynamic picture of an industry in transition. The paper has a double aim: discuss the fuzzy frontier between imitation and innovation, and track the new contours of the pharmaceutical industry.     

A cost-effectiveness analysis comparing the originator follitropin alfa to its biosimilars in patients undergoing a medically assisted reproduction program from a French perspective

Objective: To assess the cost-effectiveness (CE) of the originator follitropin-α (Gonal-F) in patients undergoing a medically assisted reproduction (MAR) program in comparison to its biosimilars Bemfola and Ovaleap in a French context.

Methods: A CE model was developed for France with a National Health Service (NHS) perspective. Clinical, safety, and dosage data were derived from pivotal clinical trials that compared Gonal-F to Ovaleap and Bemfola. Costs pertaining to drugs, hospitalizations, specialist visits, and examinations were retrieved from the French Programme de Médicalisation des Systèmes d'Information (PMSI) hospital database, literature review, and French clinical experts using 2017?Euro tariffs. In order to test the robustness of results, deterministic one-way sensitivity analyses were carried out on the main variables to assess the impact of treatment cost, probability of birth, ovarian hyperstimulation syndrome (OHSS) rates, and dosage.

Results: The average incremental cost per live birth with OHSS and without OHSS was €259.56 and €278.39, respectively, for Gonal-F compared to the pooled biosimilars (i.e. Ovaleap and Bemfola). GONAL-F had an incremental efficacy of 0.06 over the pooled biosimilars. The incremental cost-effectiveness ratio for Gonal-F with OHSS ranged from €3,274.80 to €4,877.76 compared to the pooled biosimilars, owing to the additional live births reported with Gonal-F. Sensitivity analyses also supported results from the base case analyses, with Gonal-F being cost-effective or the dominant strategy in most cases.

Conclusion: Gonal-F seems to be a cost-effective strategy compared to its biosimilars Ovaleap and Bemfola, irrespective of the incidence of OHSS events, but further data are needed to confirm these results.     

Biosimilars in Germany: the emergence of a new industry in the light of the varieties of capitalism approach

ABSTRACT

Although lagging behind the USA in biologics, German firms are forging ahead in the emerging field of biosimilars. This development confirms earlier explanations of the differences in these industries given by the Varieties of Capitalism approach. With the recent differentiation in biopharmaceuticals, again, the differences in the institutional environment on both sides of the Atlantic are responsible for different dynamics. However, this time German companies are in the better position: the industry refers to a tradition of engineering capabilities in chemicals and pharmaceuticals. Additionally, European regulation introduced the world’s first regulatory framework, which moreover is designed in a progressive way concerning market admission.     

Biosimilars in North America

ABSTRACT

The United States (US) is the world leader in the development of biopharmaceutical products. These new drugs, numbering about 200, are now losing patent protection and imitators are entering the market of comparable drugs, called biosimilars. According to a popular belief, these producers of biosimilars (erroneously called copycats) are everywhere, except in the United States. In North America, on both sides of the US border, the increase in the number of biosimilar producers is evident. In addition, although the US federal government tries to erect barriers against the entry of foreign-made biosimilars in the country, many states are lobbying the federal government and allowing the use of biosimilars. And biosimilars represent a very convenient ladder for emergent and industrial countries to learn the enigmatic routines of the pharmaceutical industry. Where this segment of the industry will be located is another matter.     

Costs associated with non-medical switching from originator to biosimilar etanercept in patients with rheumatoid arthritis in the UK

Abstract

Aims: To estimate the cost impact of non-medical switching from originator to biosimilar etanercept in stable patients with rheumatoid arthritis (RA) in the UK.

Materials and methods: A cohort-based decision tree model was developed with a 1-year time horizon. The model population included patients with stable RA (patients who responded to originator etanercept treatment with no treatment changes in the previous 6?months). Patients could undergo a non-medical switch to a biosimilar and then switch treatment again, if medically required, after 3–6?months. Data on the proportion of patients switching therapies, baseline healthcare resource use, and impact of switching on resource use were sourced from a survey of 150 rheumatologists from EU5 markets (France, Germany, Italy, Spain, UK). The average impact of switching was evaluated as mean values for change in resource utilization due to switching. Also, low- and high-impact scenarios (lower and upper values of the 95% confidence intervals for change in resource utilization due to switching) were modelled as sensitivity analyses. Cost data came from published UK sources.

Results: The model assumed that 5,000 patients were treated with originator etanercept, with 1,259 (25.2%) switching to a biosimilar. Of those, 875 (69.5%) and 384 (30.5%) switched to SB4 and GP2015, respectively. After 3?months, 26.3% of patients who switched treatments did so again: 8.3% back to originator, 3.8% to the other biosimilar, and 14.2% to another biologic. Although originator etanercept was more expensive than the biosimilars, switching was more costly than continuous originator treatment across all impact scenarios. Switching treatment chains had higher overall annual per-patient costs than continuous originator treatment. Switching was associated with increased healthcare resource use.

Limitations: Results from this analysis are not transferable to other (non-RA) etanercept indications.

Conclusion: Non-medical switching can result in increased payer costs because of increased healthcare resource use following switching.     

Health economics of market access for biopharmaceuticals and biosimilars

Abstract

Background and scope: This article discusses health economic challenges of research and development, registration, pricing and reimbursement of biopharmaceuticals and biosimilars. A literature search was carried out of PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews and EconLit up to March 2009.

Findings: The development process of biopharmaceuticals is risky, lengthy, complex and expensive. Registration is complicated by the inherent variation between biopharmaceuticals. Also, as biopharmaceuticals are likely to be efficacious in a subgroup of the patient population, there is a need to select the most responsive target population and to identify biomarkers. To inform pricing and reimbursement decisions, the development process needs to collect comparative data to calculate the incremental cost effectiveness and budget impact of biopharmaceuticals. There is a role for innovative mechanisms such as risk-sharing arrangements to reimburse biopharmaceuticals.

Conclusions: Given that biosimilars are similar, but not identical to the reference biopharmaceutical, the development process needs to generate clinical trial data in order to gain marketing authorisation. From a health economic perspective, the question arises whether inherent differences between biopharmaceuticals and biosimilars produce differences in safety, effectiveness and costs: to date, this question is unresolved. The early inclusion of health economics in the process of developing biopharmaceuticals and biosimilars is imperative with a view to demonstrating their relative (cost) effectiveness and informing registration, pricing and reimbursement decisions.     

Assessment of Resource Use and Costs Associated with Parathyroidectomy for Secondary Hyperparathyroidism in End Stage Renal Disease in the UK

Introduction:

Secondary hyperparathyroidism (SHPT) is a major complication of end stage renal disease (ESRD). For the National Health Service (NHS) to make appropriate choices between medical and surgical management, it needs to understand the cost implications of each. A recent pilot study suggested that the current NHS healthcare resource group tariff for parathyroidectomy (PTX) (£2071 and £1859 in patients with and without complications, respectively) is not representative of the true costs of surgery in patients with SHPT.

Objective:

This study aims to provide an estimate of healthcare resources used to manage patients and estimate the cost of PTX in a UK tertiary care centre.

Methods:

Resource use was identified by combining data from the Proton renal database and routine hospital data for adults undergoing PTX for SHPT at the University Hospital of Wales, Cardiff, from 2000–2008. Data were supplemented by a questionnaire, completed by clinicians in six centres across the UK. Costs were obtained from NHS reference costs, British National Formulary and published literature. Costs were applied for the pre-surgical, surgical, peri-surgical, and post-surgical periods so as to calculate the total cost associated with PTX.

Results:

One hundred and twenty-four patients (mean age?=?51.0 years) were identified in the database and 79 from the questionnaires. The main costs identified in the database were the surgical stay (mean?=?£4066, SD?=?£,130), the first month post-discharge (£465, SD?=?£176), and 3 months prior to surgery (£399, SD?=?£188); the average total cost was £4932 (SD?=?£4129). From the questionnaires the total cost was £5459 (SD?=?£943). It is possible that the study was limited due to missing data within the database, as well as the possibility of recall bias associated with the clinicians completing the questionnaires.

Conclusion:

This analysis suggests that the costs associated with PTX in SHPT exceed the current NHS tariffs for PTX. The cost implications associated with PTX need to be considered in the context of clinical assessment and decision-making, but healthcare policy and planning may warrant review in the light of these results.     

Switching of biologic disease modifying anti-rheumatic drugs in patients with rheumatoid arthritis in a real world setting

Objectives:

This study examined total healthcare costs and rates of patients with rheumatoid arthritis (RA) who switch biologic disease-modifying anti-rheumatic drug (bDMARD) therapy in a real world setting.

Methods:

A retrospective longitudinal analysis was conducted in patients with RA using IMS PharMetrics Plus database from 1/1/2004 to 3/31/2010. The first-line cohort included patients newly initiated on abatacept or the tumor necrosis factor-alpha inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab, with 12 months of continuous follow-up. The second-line cohort included patients initiating a bDMARD with evidence of a different bDMARD within the previous 2 years and with 12 months of continuous follow-up. Switching was defined as a different bDMARD claim within a 200% gap in days supply from the previous bDMARD claim. Non-switchers stayed on their bDMARD in the follow-up period. Monthly total healthcare costs for switchers and non-switchers and rates of bDMARD switching were examined. Switch rates for each bDMARD were also compared.

Results:

First-line switchers had significantly higher monthly total healthcare costs after the switch than non-switchers ($3759 vs $2343; p?p?Limitations:

There are no clinical data available in this database and, therefore, this study did not examine the clinical drivers of healthcare costs and switch rates.

Conclusions:

Monthly total healthcare costs were higher for bDMARD switchers following the switch compared to non-switchers. Patients on abatacept switched less frequently than patients on anti-TNFs. This study highlights the need to identify patients who are likely to switch in order to ensure they receive the appropriate therapy which may improve outcomes and decrease healthcare costs.     

Budget impact of pasireotide LAR for the treatment of acromegaly,a rare endocrine disorder

Background:

Acromegaly is a rare disorder characterized by the over-production of growth hormone (GH). Patients often experience a range of chronic comorbidities including hypertension, cardiac dysfunction, diabetes, osteoarthropathy, and obstructive sleep apnea. Untreated or inadequately controlled patients incur substantial healthcare costs, while normalization of GH levels may reduce morbidity and mortality rates to be comparable to the general population.

Objective:

To assess the 3-year budget impact of pasireotide LAR on a US managed care health plan following pasireotide LAR availability.

Methods:

Two separate economic models were developed: one from the perspective of an entire health plan and another from the perspective of a pharmacy budget. The total budget impact model includes costs of drug therapies and other costs for treatment, monitoring, management of adverse events, and comorbidities. The pharmacy cost calculator only considers drug costs.

Results:

The total estimated budget impact associated with the introduction of pasireotide LAR is 0.31 cents ($0.0031) per member per month (PMPM) in the first year, 0.78 cents ($0.0078) in the second year, and 1.42 cents ($0.0142) in the third year following FDA approval. Costs were similar or lower from a pharmacy budget impact perspective. For each patient achieving disease control, cost savings from reduced comorbidities amounted to $10,240 per year.

Limitations:

Published data on comorbidities for acromegaly are limited. In the absence of data on acromegaly-related costs for some comorbidities, comorbidity costs for the general population were used (may be under-estimates).

Conclusions:

The budget impact of pasireotide LAR is expected to be modest, with an expected increase of 1.42 cents PMPM on the total health plan budget in the third year after FDA approval. The efficacy of pasireotide LAR in acromegaly, as demonstrated in head-to-head trials compared with currently available treatment options, is expected to be associated with a reduction of the prevalence of comorbidities.     

Persistence,adherence, and all-cause healthcare costs in atazanavir- and darunavir-treated patients with human immunodeficiency virus in a real-world setting

Objectives:

Atazanavir (ATV) and darunavir (DRV) are protease inhibitors approved for HIV treatment in combination with ritonavir (/r). The objectives of this study were to compare persistence (time to treatment discontinuation/modification), adherence, and healthcare costs among patients with human immunodeficiency virus (HIV) initiating ATV/r or DRV/r.

Methods:

This retrospective cohort study used commercial and Medicaid administrative insurance claims data. Patients initiating ATV/r or DRV/r from 2006–2013 with continuous enrollment for ≥6 months before and ≥3 months after initiation were included. Patients were followed from initiation until discontinuation/modification (≥30 day gap in ATV or DRV or initiation of a new antiretroviral medication), during which time adherence (proportion of days covered [PDC], with PDC ≥80% or 95% considered adherent) and per-patient per-month (PPPM) total healthcare costs were measured. DRV/r patients were propensity score matched to ATV/r patients at a 1:1 ratio to achieve balance on potentially confounding demographic and clinical factors. Commercial and Medicaid samples were analyzed separately, as were antiretroviral (ART)-naïve and experienced patients.

Results:

The final samples comprised 2988 commercially-insured and 1158 Medicaid-insured patients. There were no significant differences in hazards of discontinuation/modification between the ATV/r or DRV/r cohorts. With respect to odds of being adherent, the only marginally significant result was comparing odds of achieving PDC ≥80% among ART-naïve Medicaid patients, which favored ATV/r. All other adherence comparisons were not significant. Although ATV/r cohorts tended to have lower PPPM costs, the majority of these differences were not statistically significant.

Conclusions:

Patients with HIV treated with either ATV/r or DRV/r had similar time to treatment discontinuation/modification, adherence, and monthly healthcare costs. Results were similar across the pre-specified sub-groups. These findings are useful not only as an insight into clinical practice, but also as a resource for healthcare providers and payers evaluating treatment options for HIV+ individuals.     

Middle-ground players in dynamic imitative markets: global entry strategies of Korean firms in the biosimilars market

ABSTRACT

This study examines the strategies used to enter the biosimilars market – the emerging biogeneric market – by five Korean biopharmaceutical firms. The analysis is based on a conceptual framework that characterises the use of imitative innovation by middle-ground firms. These middle-ground firms are positioned between globally innovative firms from major developed economies and latecomer firms from large emerging economies. The study finds that the five Korean firms used three entry modes that resemble the typology of strategies commonly used in the previous catch-up stage: exploiting scale economies and specialisation. The study also reveals the risk and potential of each entry mode.     

Economic burden of thromboembolic and hemorrhagic complications in non-valvular atrial fibrillation in Algeria (the ELRAGFA study)

Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with substantial public health and economic impact on healthcare systems due to the prevention and management of thromboembolic and hemorrhagic complications. In Algeria, stroke is a leading cause of death, representing 15.6% of all deaths in 2012. Current data on the epidemiology and costs associated with non-valvular AF (NVAF) in Algeria are not available.

Methods: A three-step approach was undertaken to estimate the economic burden of NVAF in Algeria. First, a literature review identified the epidemiological burden of the disease. Second, expert clinicians practicing in Algerian hospitals were surveyed on consumed resources and unit costs of treatment and management of complications and prevention. Finally, these data were combined with event probabilities in an economic model to estimate the annual cost of NVAF prevention and complications for the Algerian healthcare system.

Results: Based on literature and demographics data, it was estimated that there are currently 187,686 subjects with NVAF in Algeria. Seventy per cent of this population was treated for prevention, half of which were controlled. Cost of prevention was estimated at 203 million DZD (€1.5 million) for drugs and 349 million DZD (€2.6 million) for examinations. Mean hospitalization costs for complications ranged between 123,500 and 435,500 DZD (€910–3,209), according to the type and severity of complications. Hospitalization costs for thromboembolic and hemorrhagic complications were estimated at 8,313 million DZD (€62 million), half of which was for untreated patients. Finally, the economic burden of NVAF was estimated at 8,865 million DZD (>€65 million) annually.

Conclusion: The economic burden of NVAF is important in Algeria, largely driven by untreated and INR-uncontrolled patients. There is a lack of information on the Algerian healthcare system that could increase uncertainty around this assessment, but it clearly establishes the importance of NVAF as a public health concern.     

Cost minimization analysis of capecitabine versus 5-fluorouracil-based treatment for gastric cancer patients in Hong Kong

Background: EOX (epirubicin, oxaliplatin, Xeloda; capecitabine) and FOLFOX4 (5-fluorouracil (5-FU), leucovorin, oxaliplatin) are the common chemotherapy regimens used in the treatment of advanced gastric cancer (aGC) in Hong Kong. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. It should be noted that, while FOLFOX4 is routinely administered in an outpatient setting in North America and Europe, inpatient setting is adopted in Hong Kong instead, incurring hospitalization cost as a result.

Methods: Fifty-eight patients were identified from the electronic records in two public tertiary hospitals, with 45 and 13 receiving EOX and FOLFOX4 regimens, respectively. Healthcare cost was direct medical costs including drugs, clinic follow-up, hospitalization, diagnostic laboratories, and radiographs. Societal cost refers to indirect costs such as patient time and travel costs. Cost items were further classified as “expected” or “unexpected”. All cost data was expressed in US dollars.

Results: Patients in the EOX and FOLFOX4 arm received an average of 5.3 and 7.8 cycles of treatment, respectively. The capecitabine-based regimen group had a higher expected medication cost per cycle when compared to the 5-FU-based treatment group (US$290.3 vs US$66.9, p?p?p?p?=?.001), respectively, in the capecitabine-based regimen group. Sensitivity analyses based on full cycle regimen costs and net capecitabine or 5-FU/leucovorin costs still showed EOX to be less costly than FOLFOX4.

Conclusion: The capecitabine-based regimen, EOX, was found to generate significant cost saving from both the healthcare and societal perspectives in regions in which FOLFOX4 is given in an inpatient setting.     

Healthcare costs in psoriasis and psoriasis sub-groups over time following psoriasis diagnosis

Aims: To quantify healthcare costs in patients with psoriasis overall and in psoriasis patient sub-groups, by level of disease severity, presence or absence of psoriatic arthritis, or use of biologics.

Methods: Administrative data from Truven Health Analytics MarketScan Research Database were used to select adult patients with psoriasis from January 2009 to January 2014. The first psoriasis diagnosis was set as the index date. Patients were required to have ≥6 months of continuous enrollment with medical and pharmacy benefits pre-index and ≥12 months post-index. Patients were followed from index until the earliest of loss to follow-up or study end. All-cause healthcare costs and outpatient pharmacy costs were calculated for the overall psoriasis cohort and for the six different psoriasis patient sub-groups: (a) patients with moderate-to-severe disease and mild disease, (b) patients with psoriatic arthritis and those without, and (c) patients on biologics and those who are not. Costs are presented per-patient-per-year (PPPY) and by years 1, 2, 3, 4, and 5 of follow-up, expressed in 2014?US dollars.

Results: A total of 108,790 psoriasis patients were selected, with a mean age of 46.0 years (52.7% females). Average follow-up was 962 days. All-cause healthcare costs were $12,523 PPPY. Outpatient pharmacy costs accounted for 38.6% of total costs. All-cause healthcare costs were highest for patients on biologics ($29,832), then for patients with psoriatic arthritis ($23,427) and those with moderate-to-severe disease ($21,481). Overall, all-cause healthcare costs and outpatient pharmacy costs presented an upward trend over a 5-year period.

Conclusions: Psoriasis is associated with significant economic burden, which increases over time as the disease progresses. Patients with moderate-to-severe psoriasis, those with psoriatic arthritis, or use of biologics contributes to higher healthcare costs. Psoriasis-related pharmacy expenditure is the largest driver of healthcare costs in patients with psoriasis.     

Real-world treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriasis

Objective: This study compared real-world treatment patterns and healthcare costs among biologic-naive psoriasis patients initiating apremilast or biologics.

Methods: A retrospective cohort study was conducted using the Optum Clinformatics? claims database. Patients with psoriasis were selected if they had initiated apremilast or biologics between January 1, 2014, and December 31, 2015; had 12?months of pre-index and post-index continuous enrollment in the database; and were biologic-naive. The index date was defined as the date of the first claim for apremilast or biologic, and occurred between January 1, 2014, and December 31, 2015. Treatment persistence was defined as continuous treatment without a?>?60-day gap in therapy (discontinuation) or a switch to a different psoriasis treatment during the 12-month post-index period. Adherence was defined as a medication possession ratio (MPR) of ≥ 80% while persistent on the index treatment. Persistence-based MPR was defined as the number of days with the medication on hand measured during the patients’ period of treatment persistence divided by the duration of the period of treatment persistence. Because patients were not randomized, apremilast patients were propensity score matched up to 1:2 to biologic patients to adjust for possible selection bias. Treatment persistence/adherence and all-cause healthcare costs were evaluated. Cost differences were determined using Wilcoxon rank-sum tests.

Results: In all, 343 biologic-naive patients initiating apremilast were matched to 680 biologic-naive patients initiating biologics. After matching, patient characteristics were similar between cohorts. Twelve-month treatment persistence was similar for biologic-naive patients initiating apremilast vs biologics (32.1% vs 33.2%; p?=?0.7079). While persistent on therapy up to 12?months, per-patient per-month (PPPM) total healthcare costs were significantly lower among biologic-naive cohorts initiating apremilast vs biologics ($2,214 vs $5,184; p?p?p?p?Limitations: Data were limited to individuals with United Healthcare commercial and Medicare Advantage insurance plans, and may not be generalizable to psoriasis patients with other insurance or without health insurance coverage.

Conclusion: Biologic-naive patients with similar patient characteristics receiving apremilast vs biologics had significantly lower PPPM costs, even when they switched to biologics during the 12-month post-index period. These results may be useful to payers and providers seeking to optimize psoriasis care while reducing healthcare costs.     

Healthcare resource utilization and costs associated with venous thromboembolism recurrence in patients with cancer

Abstract

Objective: Patients with cancer are at high risk for developing primary but also recurrent venous thromboembolism (VTE). This study examined healthcare utilization (HRU) and costs related to VTE recurrence among cancer patients.

Methods: Medical and pharmacy claims from the Humana Database were used to compare HRU (outpatient visits, emergency room visits, hospitalizations, and hospitalization days) and healthcare costs among cancer patients with a single VTE event (between 01/2013 and 06/2015) and those with recurrent VTE during the follow-up period (from initiation of anticoagulant therapy until end of eligibility or data availability). All-cause and VTE-related HRU and costs were evaluated using Poisson regression, and healthcare costs were compared using mean differences reported as per-patient-per-year (PPPY).

Results: Of 2,428 newly diagnosed cancer patients who developed VTE, 413 (17.1%) experienced recurrent VTE during the follow-up period (mean = 9 months). Patients with recurrent VTE had higher all-cause and VTE-related HRU and costs compared to those without recurrence. Patients with recurrent VTE also had over 3.19-times more VTE-related hospitalizations (RR [95% CI]?=?3.19 [2.93–3.47]), and 3.88-times more VTE-related hospitalization days (RR [95% CI]?=?3.88 [3.74–4.02]) than patients without a VTE recurrence. Total VTE-related healthcare costs were $39,641 PPPY among patients with recurrent VTE, $29,142 higher compared to those without recurrence ($10,499 PPPY). This difference was mainly driven by hospitalization costs.

Conclusion: Recurrent VTE among cancer patients is associated with significant HRU and healthcare costs, notably hospitalizations. Strategies to reduce VTE recurrence in patients with cancer can contribute to reducing healthcare cost.