Cost value analyses

A central pillar of the work done by the DKFZ Division of Health economics is the elaboration of economic evaluations, particularly cost-effectiveness analysis. Cost-effectiveness analysis evaluates the effectiveness of two or more treatments relative to their cost. Different interventions are currently included in this pillar.

Certification of hospitals providing health care for cancer patients has become an important measure to improve quality and outcomes. However, considering the significant additional costs incurred from certification, the cost-effectiveness of cancer care provided in certified hospitals was yet to be established. In cooperation with the team of Jochen Schmitt (NCT Dresden and Center for Evidence-Based Health Care at the University of Dresden), we used administrative data to derive the first health economic evidence supporting that colon cancer care delivered in certified cancer centers in Germany improves survival outcomes and saves costs from a healthcare system's perspective. Since it is not clear whether the encouraging health economic findings for patients with colorectal cancer can be generalized, as second step we have initiated an extension of the first study by looking into the cost effectiveness of medical care for breast cancer in certified cancer centers. In a third step, further extensions are planned to study additional tumor entities.

While the first publications on the cost effectiveness of CRC screening and prevention strategies are expected during 2023, health economic evaluations of breast cancer and prostate cancer screening are at an earlier stage. For breast cancer screening, there seems to be sufficient evidence that the benefits of mammography outweigh the harms for the general population. The biennial mammography recommendation in Germany applies to women of average risk, between the ages of 50 and 69, similar to other countries. However, this screening strategy might not work well for women with different risks. We developed an adaptation of the "Wisconsin Model" to conduct an economic evaluation of risk-adjusted screening strategies. For prostate cancer screening, the Division is cooperating with Peter Albers (DKFZ and University of Düsseldorf) to evaluate personalized prevention based on the PROBASE Trial. For analysis, a Swedish prostate cancer natural history model is being adapted and re-calibrated to the German setting.

Health economic evaluation alongside clinical trials offers an unparalleled opportunity to collect relevant health care resource utilization and (quality of life) utility data in addition to the clinical endpoints. A collaboration was established with NCT Heidelberg to support two clinical trials: (1) a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as an adjunct to intensive induction therapy and to compare intensive postremission therapy double-blinded with or without glasdegib in older patients with newly diagnosed AML (GnG) and (2) a randomized study in newly diagnosed AML with FLT3-ITD comparing Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib to physician's choice (Q-SOC).

Support provided included but was not limited to writing health economic-specific sections of the clinical trial project proposal, developing project-specific resource utilization questionnaires, selecting and administering appropriate multi-attributable utility measures, and training clinical staff on how to administer health economic-related questionnaires during clinical trials. Both trials were discontinued by the clinical project partners for reasons unrelated to health economics, and no data are available for further economic analyses. The Division, nevertheless, continues to offer support of clinical studies to include the option of health economic evaluations on their back.

A BMG-funded research project, the "Tumor Behavior Prediction Initiative" (TPI) under the leadership of Titus Brinker (DKFZ), aims to generate new biomarkers that will have the potential to enable long-term personalized cancer treatment for patients with various cancer types including melanoma, breast cancer or colorectal cancer. The Division of Health Economics contributes to this collaborative research project by evaluating the potential value of the routine use of AI-based digital biomarkers in clinical practice.

In the Skin Classification Project, also led by Titus Brinker (DKFZ), convolutional neural networks (CNNs) were designed and trained to support melanoma diagnosis. The Division of Health Economics evaluated the potential economic value of introducing such new diagnostic algorithm in everyday clinical practice by designing an early-phase economic model. The initial estimates predicted potential cost savings in the magnitude of €7m from the perspective of the German statutory health insurance using the AI-based assistance system – based on retrospective data.

In a follow-up project (Skin Classification Project II) further analyses are being conducted to address the limitations of the early economic evaluation and to provide more precise cost-effectiveness estimates of the diagnostic algorithm based on clinical data from a multicenter prospective study. The ongoing evaluation is designed to assess various scenarios and potential outcomes of a real-world implementation through model-based analysis.

The Division of Health Economics is participating in an EU-level collaborative research project, Building Data Rich Clinical Trials ("CCE-DART"), to conduct methodological research around targeted therapies and innovative clinical trial designs. The project aims to improve the design and implementation of clinical trials. Cancer research is rapidly evolving with the proliferation of molecular targeted therapies, and new types of adaptive, basket, and umbrella trials came to fore to assess innovative treatments tied to the existence of selected biomarkers rather than histology. Yet, there is a lack of sound methodological basis for health economic evaluations alongside new clinical trial designs. Through the "Basket of Baskets" (BoB) case study, we are investigating how clinical data from such trials can be incorporated in health economic evaluations to provide meaningful outcomes for health policy decision making on such treatment approaches.

The Division responded to the proclaimed strategic focus area at the DKFZ, "cancer prevention", by launching three major modeling initiatives for the economic assessment of screening and prevention strategies in colorectal (CRC), breast, and prostate cancer, respectively. In all three cases, a robust long-term approach was chosen using advanced microsimulation techniques instead of simpler Markov cohort models still widely used.

Existing CRC screening models mostly focus on the adenoma pathway of cancer development, thus overlooking the serrated neoplasia pathway, which might result in overly optimistic screening predictions. The Division developed a CRC screening model accounting for both pathways, calibrated it with approximate Bayesian computation (ABC) methods, and validated it with large CRC screening trials. The discrete event simulation (DES) model has been used as a tool to evaluate the (cost-)effectiveness of CRC screening strategies.

While the first publications on the cost effectiveness of CRC screening and prevention strategies are expected during 2023, health economic evaluations of breast cancer and prostate cancer screening are at an earlier stage. For breast cancer screening, there seems to be sufficient evidence that the benefits of mammography outweigh the harms for the general population. The biennial mammography recommendation in Germany applies to women of average risk, between the ages of 50 and 69, similar to other countries. However, this screening strategy might not work well for women with different risks. We developed an adaptation of the "Wisconsin Model" to conduct an economic evaluation of risk-adjusted screening strategies. For prostate cancer screening, the Division is cooperating with Peter Albers (DKFZ and University of Düsseldorf) to evaluate personalized prevention based on the PROBASE Trial. For analysis, a Swedish prostate cancer natural history model is being adapted and re-calibrated to the setting for Germany.

Selected Publications:

C.-Y. Cheng, S. Calderazzo, C. Schramm, M. Schlander
Modeling the natural history and screening effects for colorectal cancer using both adenoma and serrated neoplasia pathways: the development, calibration, and validation of a discrete event simulation model.
MDM Policy & Practice, 2023: 8(1), published 21 Jan 2023.
DOI: 10.1177/23814683221145701.

C. -Y. Cheng, T. Datzmann, D. Hernandez, J. Schmitt, M. Schlander:
Do certified cancer centers provide more cost-effective care? A health economic analysis of colon cancer care in Germany using administrative data.
International Journal of Cancer, 2021: 149 (10) 1744-1754.
DOI: 10.1002/ijc.33728.

A. Deibel, L. Deng, C. -Y. Cheng, M. Schlander, T. Ran, B. Lang, N. Krupka, N. Beerenwinkel, G. Rogler, R. Wiest, A. Sonnenberg, J. Poleszczuk, B. Misselwitz:
Evaluating key characteristics of ideal colorectal cancer screening modalities: the microsimulation approach.
Gastrointestinal Endoscopy, 2021: 94 (2) 379-390.e7.
DOI: https://doi.org/10.1016/j.gie.2021.02.013.

S. A. Khan, K. Hernandez-Villafuerte, D. Hernandez, M. Schlander:
Estimation of the stage-wise costs of breast cancer in Germany using a modeling approach.
Frontiers in Public Health, 2023: 10, published 6 Jan 2023.
DOI: 10.3389/fpubh.2022.946544.

S. A. Khan, K. V. Hernandez-Villafuerte, M. T. Muchadeyi, M. Schlander:
Cost-effectiveness of risk-based breast cancer screening: A systematic review.
International Journal of Cancer, 2021: 149 (4) 790-810.
DOI: 10.1002/ijc.33593.

A. Molnar, T.J. Brinker, A. Hekler, K.V. Hernandez-Villafuerte, M. Schlander:
Direct costs related to medical management of malignant cutaneous melanoma through the patient pathway.
Poster presentation at ISPOR Europe 2020.
Virtual. November 16-19, 2020.
Value in Health, 2020 23(Supplement 2) S460.
DOI: 10.1016/j.jval.2020.08.348.

M. Schlander:
Risikoadaptierte Früherkennung & Prävention.
Invited oral presentation at the 35th German Cancer Congress (DKK).
Berlin, Germany. November 13-16, 2022.

M. Schlander, C.-Y. Cheng, T. Ran:
The health economics of cancer screening in Germany: Which population-based interventions are cost-effective? [Gesundheitsökonomie der Krebsfrüherkennung in Deutschland: Welche Interventionen sind kosteneffektiv bei bevölkerungsweiter Umsetzung?]
Bundesgesundheitsblatt, (2018) 61(12) 1559-1568.
DOI: 10.1007/s00103-018-2839-3.

In practice, HTA rests predominantly on two pillars: the assessment of clinical benefit drawing on principles of evidence-based medicine, and an evaluation of efficiency, usually by means of some variant of cost-effectiveness analysis (CEA). For example, well-known HTA agencies as the British National Institute for Health and Care Excellence (NICE) and the German Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) have implemented different evaluation approaches, which (may) also reflect variations in HTA outcomes. An HTA comparative study was conducted to explore the extent to which different methodological choices are associated with different HTA outcomes. The study mainly focused on assessment and appraisal results as well as (official and unofficial) evaluation criteria by G-BA and NICE, respectively. In a follow-up project, we consider systematically reviewing the data requirements of official HTA agencies, including their acceptance of data sources and handling of potential bias.

Selected Publications:

R. Schaefer, D. Hernandez, T. Bärnighausen, P. Kolominsky-Rabas, M. Schlander:
The HTA-informed Decision-Making by GBA/IQWiG in Germany and NICE in England: The Role of Budget Impact.
Value in Health, 2023 (in press).

R. Schaefer, D. Hernandez, L Selberg, M. Schlander:
Health technology assessment (HTA) in England, France and Germany: what do matched drug pairs tell us about recommendations by national HTA agencies?
Journal of Comparative Effectiveness Research, 2021: 10 (16) 1187-1195.
DOI: 10.2217/cer-2021-0047.

R. Schaefer, M. Schlander:
Is the National Institute for Health and Care Excellence (NICE) in England more ´innovation-friendly´ than the Federal Joint Committee (GBA) in Germany?
Expert Review of Pharmacoeconomics & Outcomes Research, 2019: 19 (4) 453-462.
DOI: 10.1080/14737167.2019.1559732.

T. Ran, C.-Y- Cheng, B. Misselwitz, H. Brenner, J. Ubels, M. Schlander:
Cost–effectiveness of colorectal cancer screening strategies: A systematic review.
Clinical Gastroenterology and Hepatology, 2019: 17 (10) 1969-1981.
DOI: 10.1016/j.cgh.2019.01.014.

R. Schaefer, M. Schlander:
Is the National Institute for Health and Care Excellence (NICE) in England more ´innovation-friendly´ than the Federal Joint Committee (GBA) in Germany?
Expert Review of Pharmacoeconomics & Outcomes Research, (2019) 19 (4) 453-462.
DOI: 10.1080/14737167.2019.1559732.