Background
Lung cancer is one of the most common causes of cancer-related death in both men and women in Germany [
1‐
3]. In 2016 alone, lung cancer claimed the lives of 29,324 men and 16,481 women in Germany. According to the Federal Robert Koch Institute (Berlin), this corresponds to a standardized death rate of 45.7 for men and 22.6 for women [
4].
A histological distinction is made between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [
1‐
3]. NSCLC dominates in terms of incidence, accounting for around 80% of all malignant lung tumors [
1,
2,
5]. SCLC, by contrast, has a significantly lower incidence rate of 20% [
1,
3,
6] but is prognostically even less favorable due to early lymph node and distant metastasis, which is also reflected in significantly lower survival rates compared to NSCLC [
5,
6]. Since most lung cancers are usually only diagnosed at an advanced stage, prompt, targeted therapeutic or palliative intervention is required [
7]. This poses a considerable challenge for therapists. This aspect, together with the large number of people affected, suggests that developing and ensuring adequate needs-based care is of paramount importance for patients.
In recent years the focus has increasingly been placed on the use of “real-world data” (RWD) [
8‐
11]. RWD provide insights into the realities of daily practice as well as the patient population relevant to everyday life, including individual differences between patients. RWD also include data compiled in the healthcare databases of statutory health insurance (SHI) funds and health registers [
12].
In Germany, the analysis of the healthcare data of SHI patients is used cautiously [
9,
13], although it is a good way to model the routine care of patients. For example, the German variant of the ICD-10 coding of the World Health Organization (WHO) [
14] (ICD-10-German Modification / GM) allows patients to be specifically identified on the basis of the coded clinical picture. The associated anonymized healthcare data can be consulted to analyze the use of medical interventions and prescription drugs in routine practice as described by aggregated data. Such a retrospective analysis of the healthcare situation of patients can be taken into account when shaping statutory healthcare policies. It can also form the basis for modifying statutory services. The use of health data from SHI funds is particularly useful in the case of high-prevalence clinical pictures, such as lung cancer, as it can help to identify options for improving the needs-based care of patients. Such was the aim of the observational, retrospective, longitudinal analysis of structured data presented here. It evaluated the healthcare data of SHI patients who were diagnosed with lung cancer in 2015 and 2016. Another goal was to develop an algorithm that allows conclusions to be drawn about the respective cancer types (NSCLC vs. SCLC) based on the billing data of SHI patients. This facilitates the acquisition of new knowledge about the diagnosis of lung cancer with the help of the SHI databases.
Discussion
The present analysis served to retrospectively evaluate the healthcare situation of patients with statutory health insurance diagnosed with lung cancer in Germany on the basis of billing data from 64 statutory health insurance funds. The aim was to gain new knowledge for improved needs-based care delivery. The external validity of the database used was proven based upon a comparison to the German population as previously shown in terms of morbidity, mortality and drug usage. The database population used was slightly younger than the German population. Also, the proportion of members living in the eastern part of Germany was lower in the database used [
15]. Targeted analyzes of the healthcare data on the extent of the relevant disease, the treatment strategies, and the use of new treatment methods, as well as the patients’ impairment of freedom due to illness and treatment provide a way to model the real-world routine clinical situation [
11]. In the context of the German healthcare system, the hitherto rare analysis [
13] of healthcare databases can help to identify and specify needs-based care services. The results of the analysis can also serve as a basis for discussing the healthcare services required for the diagnosis and treatment of lung cancer. An algorithm is required to specifically filter out the relevant patients within a healthcare database and thus permit a retrospective analysis and evaluation of the healthcare situation of large patient groups. One of the aims of the present analysis was therefore to establish this approach taking lung cancer as an example. Based on the ICD-10-GM coding as well as the EBM or OPS code, and the ATC classification of prescription drugs, which were documented by the therapist for billing purposes, it should be possible to draw conclusions about the cancer type present, as this is of crucial relevance to the type of treatment, the patient’s needs, and the further course of treatment. However, it turned out that at present, such assignment is only possible on basis of the healthcare data to a limited degree. Using the gold standard as cancer registries or electronic medical charts, it may be possible to develop an algorithm with high accuracy, but there was no gold standard for this study. Only a quarter of the total population could be reliably assigned in this way (NSCLC patients: 19.6%, SCLC patients: 6.4% of the total population). By contrast, an algorithm was developed for NSCLC patients in the USA which is based on clinical parameters [
28]. It was therefore originally assumed that a similar algorithm to be developed de novo for the German health service context could also be applied to a German healthcare database. That was not the case. Reasons why this was not possible may be due to differences in coding practice in Germany. Although both, outpatient and inpatient treatment was observable in the data, there are no codes for laboratory examinations, and in contrast to the US, it is not possible to match the data with registries. Moreover, elderly persons might be less precisely diagnosed, and the treatment options may be more limited due to comorbidities and their general age-related health status [
29,
30]. Further analyses in this area are required in order to identify and validate suitable variables of a filter algorithm. Current efforts to link healthcare and research may help to find better answers [
31].
With regard to the treatment of the patients, most received standard therapy. It was noteworthy, however, that chemotherapy was used during first-line therapy for both NSCLC patients and SCLC patients (NSCLC patients: 71.4%, SCLC patients: 90.9%). Based on the current approval status, it was expected that the patients could be assigned to one of the two cancer types based on the coded drugs. For example, the treatment of SCLC relies on a platinum-based combination therapy with concomitant radiation [
3,
7], so that the service items in the billing should be clear. However, the small number of patients who can be assigned suggests that many patients are treated off label. In agreement with the literature, and as per German Off-label allowance, it should be mentioned that carboplatin (in lung cancer licensed for SCLC patients only in Germany) can be prescribed off-label for NSCLC [
2,
32‐
34]. In summary, no generally applicable algorithm for the selection of the patients concerned can currently be developed. However, it is expected that progress made in recent years towards personalized precision therapy for patients with lung cancer will allow a clearer assignment of patients based on documented billing data in the future.
In addition to drug-based therapy, surgical intervention is also a treatment option for lung cancer. In SCLC, this treatment approach is only recommended in stages I–II (very limited disease) [
3,
6]. In NSCLC, by contrast, surgery can be part of the therapy at various stages [
2,
6]. This explains the greater incidence of surgical intervention among NSCLC patients compared to SCLC patients. Overall, however, the number of patients with a documented surgical intervention was low, which is probably due to the fact, that many patients in the analysis population were only diagnosed at a late stage (i.e., with distant metastases, stage IV), when surgery is no longer indicated.
With regard to the diagnosis of lung cancer, the majority of the patients were initially coded during hospitalization. This is because around 90% of lung cancer patients initially show symptoms of the disease which are caused by the primary tumor and/or metastases already present [
6]. After the first visit to the primary-care physician or pulmonologist, they are referred to a specialist center for further diagnostic clarification and confirmation of the suspected diagnosis. Since bronchoscopy is required for this purpose, and since this is usually done in an inpatient setting, the diagnosis is usually first coded in a hospital. With regard to the question of inpatient/outpatient care, a bias cannot be ruled out due to the hierarchy of the treating institutions applied in this analysis. For example, many pulmonologists working in the field of oncology are based in the specialist centers, so that although they make the diagnosis per se, in the present analysis “inpatient hospital” stays took precedence as the therapist. Due to the time-consuming diagnostics involved, a hospital stay of several days is usually required for those patients, which in turn explains the predominance of inpatient hospital stays in the initial coding compared to outpatient hospital stays.
Bronchoscopy is very important as part of the diagnosis itself [
6,
35]. The majority of NSCLC and SCLC patients underwent bronchoscopy (NSCLC patients: 82.7%, SCLC patients: 80.8%). All bronchoscopies, regardless of their assignment to one of the cancer types, were also performed in a hospital setting. It was noteworthy in the present analysis that almost 78% of the unclassifiable patients and patients receiving “other therapy” did not undergo bronchoscopy. A reason why bronchoscopy was not documented for those patients can be that bronchoscopy in a study setting may be performed more frequently than in real world and thus be reimbursed by the sponsor of the study. Also, bronchoscopy is not required in the presence of distant metastases, e.g., in the liver, that have been histologically confirmed by liver biopsy. It should be noted that regarding determination of cancer type apart from the bronchoscopy, the present analysis only evaluated billing related to testing for biomarkers, so that it remains open whether there were other, possibly individual-related, reasons that supported lung cancer diagnosis and treatment for the unclassifiable patients.
It was noteworthy in the present analysis that biomarker testing was only documented for a small percentage of NSCLC patients (10.9% of NSCLC patients). This lack of data on biomarker test results is a limitation in the current analysis. Biomarker testing, e.g. for EGFR or ALK, is only recommended for non-squamous NSCLC, and differentiation from squamous NSCLC is not possible on the basis of the available data (see above) [
2,
6,
35]. With regard to the treatment group, most of the biomarker tests were carried out in the “inhibitor therapy” group. This is understandable because the inhibitor is selected on the basis of the test results. Histopathological PD-L1 testing is not usually billed separately. Another reason for the poor testing rate may be due to the remuneration situation. Biomarker testing in a hospital setting is not reimbursed by the statutory health insurance funds. Another reason could also be that testing was carried out during the observation period in connection with large collaborative projects such as the Network Genomic Medicine Lung Cancer [
36], or was billed via separate (integrated care) contracts, so that they were not included in the underlying data. The number of tests actually carried out could therefore be significantly higher than the results of the present analysis would indicate. This is also supported by the results of the German Lung Cancer Registry’s CRISP study (Clinical Research Platform into Molecular Testing, Treatment and Outcome of (Non)-Small Cell Lung Carcinoma Patients) [
37]. The aim of CRISP is to collect valid and representative routine healthcare and quality-of-life data in order to reflect the current clinical reality of patients with metastatic NSCLC. Latest results have shown that around 83% of the lung cancer patients included in the cohort study (
n = 2.204) were tested for EGFR, ALK, ROS-1, PD-L1 and / or BRAF [
37].
The diagnosis of lung cancer usually has far-reaching consequences for those affected [
38,
39]. Since the diagnosis is usually only made at an advanced or metastatic stage, the resulting limited prognosis requires rapid intervention. This involves hospital stays for diagnostic testing and treatment, visits to primary-care physicians and specialists, and visits to pharmacies. This results in a treatment-related impairment of freedom of the patient, which is added to the burden caused by the diagnosis itself. The present analysis shows that treatment-related impairment of freedom increased greatly in the index quarter as well as in the first quarter after diagnosis. In the index quarter, this is due largely to hospitalizations for diagnostic testing and subsequent treatment (surgery, chemotherapy, radiation). The number of visits to a specialist, however, increased significantly after the index quarter, regardless of the lung cancer type identified. This is also related to the treatment given. Both chemotherapy and radiotherapy are carried out on an outpatient basis in Germany, which has led to an increase in specialist visits. In Germany, oral cancer drugs, which are administered on an outpatient basis in a practice, are obtained by the patients themselves at a pharmacy. Consequently, there is a significant increase in pharmacy visits in the index quarter and in the following quarter, which is also reflected in the present analysis. With regard to cancer type, it was found that the time taken up by illness and treatment, especially for SCLC patients, is characterized by specialist visits. Because SCLC patients usually receive platinum-based chemotherapy [
3,
6], and because this is carried out on several consecutive days per week, the number of specialist visits is particularly high for those patients. In the case of NSCLC, on the other hand, the time span between the individual infusions is several weeks (immunotherapeutic agents). Some of the drugs are also given orally (inhibitors). Thus, both therapeutic approaches require a specialist visit much less often [
3].
Another aspect of needs-based care for lung cancer patients is the division of the supply infrastructure. In rural areas in Germany, the density of physicians is declining [
40], which can lead to greater, treatment-related impairment of freedom compared to patients in the urban population. The present analysis shows that the majority of lung cancer patients live in urban areas. Besides smoking, various environmental factors are also responsible for the development of lung cancer. It is therefore suspected that the demonstrably higher exposure of people in urban areas to carcinogenic environmental factors may also lead to an increased number of lung cancer cases in urban areas [
41]. However, the present analysis does not allow any valid conclusions to be drawn with regard to this question. In terms of treatment-related impairment of freedom, there were only marginal differences between patients in rural and urban areas. Similar results were also obtained in a recently published German study investigating whether the region of residence results in differences in the supportive care of lung cancer patients [
42]. In the present analysis, only the number of specialist visits was significantly higher for SCLC patients in rural areas compared to those in urban areas. This may be due to age structure and associated comorbidities [
43]. Overall, the treatment-related impairment of freedom is highest in the index quarter and in the following quarter irrespective of the cancer type and geographical distribution. This time period may therefore be the starting point for improving the current situation. Moreover, thanks to newer therapeutic approaches for the treatment of NSCLC, the number of specialist visits can be reduced, since drug administration is required less frequently in comparison to conventional chemotherapy.
Declarations
Competing interests
Sina Neugebauer is employee of MSD SHARP & DOHME GMBH, Munich, Germany.
Frank Griesinger has disclosures from the following companies: Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Lilly, Medac, Merck, MSD, Novartis, Pfizer, Roche and Takeda.
Sabine Dippel is employee of Organon GmbH, Luzern, Switzerland. At the time of the manuscript development Sabine Dippel was employed at MSD MERCK SHARP & DOHME AG, Luzern, Switzerland. At the time of study conduct, Sabine Dippel was employed at MSD SHARP & DOHME GMBH, Haar, Germany.
Stephanie Heidenreich is employee of MSD SHARP & DOHME GMBH, Munich, Germany.
Nina Gruber is employee of MSD SHARP & DOHME GMBH, Munich, Germany.
Detlef Chruscz is employee of CONVEMA, which was retained as paid analyst by MSD SHARP & DOHME GMBH to conduct this research.
Sebastian Lempfert is managing director of HCSL Healthcare Consulting e.K., which was retained as paid consultant by MSD SHARP & DOHME GMBH.
At the time the study was designed and executed and the manuscript developed and finalized, Peter Kaskel was employee of MSD SHARP & DOHME GMBH, Haar, Germany. Peter Kaskel has ownership interests with MERCK & CO., INC., Kenilworth, NJ, USA.
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