This article aims to describe the conjoint analysis (CA) method and its application in healthcare settings, and to provide researchers with a brief guide to conduct a conjoint study. CA is a method for eliciting patients’ preferences that offers choices similar to those in the real world and allows researchers to quantify these preferences. To identify literature related to conjoint analysis, a comprehensive search of PubMed (MEDLINE), EMBASE, Web of Science, and Google Scholar was conducted without language or date restrictions. To identify the trend of publications and citations in conjoint analysis, an online search of all databases indexed in the Web of Science Core Collection was conducted on the 8th of December 2021 without time restriction. Searching key terms covered a wide range of synonyms related to conjoint analysis. The search field was limited to the title, and no language or date limitations were applied. The number of published documents related to CA was nearly 900 during the year 2021 and the total number of citations for CA documents was approximately 20,000 citations, which certainly shows that the popularity of CA is increasing, especially in the healthcare sciences services discipline, which is in the top five fields publishing CA documents. However, there are some limitations regarding the appropriate sample size, quality assessment tool, and external validity of CA. The popularity of conjoint analysis (CA) in health outcomes research has been increasing in recent years ,2. Yet, One of the main methods of examining patients’ preferences is the CA, which was developed to scrutinize preferences within the decision-making process ,13. CA iThe term CA generally belongs to the description of the variety of quantitative methods used to analyze preferences ,20. The When people are making treatment decisions, they base their choice on several characteristics of this treatment. CA assumes that each one of these characteristics has a specific importance to people and they are making trade-offs between these characteristics ,23. It iCA methods use three main approaches and tools to elicit well-ordered preferences: ranking, rating, or discrete choices . When coThis article aims to provide an overview of the CA method and analyze the growth of its application over the past 70 years. It also narratively discusses the literature of the CA method’s process and validity, its use in healthcare settings, and its strengths and limitations.A comprehensive literature search was conducted. Following Gasparyan and colleagues’ recommendations , PubMed The Web of Science Core Collection (WoSCC) was utilized to identify the trend of publications and citations over the past 70 years. WoSCC is a database providing access to billions of cited references dating back to 1900 in the areas of life sciences, social sciences, arts, and humanities , and is The WoSCC search identified a total of 9614 documents related to CA, which were published between 1950 and the 8th of December 2021. The result of the search demonstrated a significant increase in the production and citation of published papers related to CA over the years to reach nearly 900 documents and 20,000 citations in 2020 and 2021 see . The graThe results of the citations analysis indicated that the business and economics field has the highest number of publications of CA. This is expected, as CA originated from this area of research, more specifically for marketing research. It is not surprising that the healthcare field of research was one of the top five areas publishing papers on CA topics. This indicates the growing interest in the CA method by healthcare researchers see . In termDuring the 1990s, the initial focus of researchers was to assess patient preferences and satisfaction regarding the treatment outcome only . This waAttributes are known to be the factors, features, or characteristics which are believed to influence people’s preferences for a particular product or treatment ,41. IdenIn CA, each attribute is defined by a series of levels . TherefoOnce the attributes and levels are identified, the levels of all attributes are combined to form all possible scenarios. CA tasks are the mechanism by which possible profiles are presented to respondents for preference elicitation . The higPeople’s preferences of the developed scenarios can be established using a rating, ranking, or choice-based approach. The ranking approach in In In CA methods, regression techniques are used to estimate the relative importance of the attributes and the utilities (part-worths) of the levels ,23. MoreSeveral traditional quantitative and qualitative methods have been used to study patients’ preferences. However, these studies were limited in number . These mNowadays, there has been a rapid increase in the use of CA to quantify preferences for various healthcare services and treatment options . For exaIn the hospital setting, implementation of CA constituted a feasible and useful tool in several clinical areas such as investigating hospital stakeholders’ decision-making in the adoption of evidence-based interventions , elicitiThroughout the discussed CA-based studies, we can discern that CA is a major asset for valuing patients’ important contributions in the decision-making process by assessing patients’ preferences in accordance with treatment selection, patient care, offered health services, and cost comparisons. Research-based literature verified that CA can be a practical method of estimating utility for any combination of attributes, including combinations representing goods or services which may not currently be available . Thus, wExternal validity is the ability of the CA tool to predict what people would choose in real life. This can be achieved by asking the question “did people choose what CA predicted?”. For example, in a conjoint study estimating the market share for an American multinational telecommunications corporation, various trial simulations were implemented hypothesizing that several product features had to be changed in order to attain desired sales  . Four yeInternal consistency validity is the main validity criterion that has been studied in recent years for strengthening the reliability and applicability of CA. To test the internal validity, the holdouts’ choices are used . The holRecently, it has been suggested that the value of CA is not only related to its elevated frequency of implementation but also to the unique ability of this method to generate individuals’ preferences realistically enough to match various decision-making processes faced by individuals in the real world . AssessiGenerally, as the use of CA in the healthcare setting increased, some validity studies were performed to approach more patients’ preferences and expectations. These were not focused only on the patients’ benefit–risk trade-offs, but also on evaluating the patients’ WTP for treatments or services .Over the years, CA design enabled researchers to elicit and quantify patients’ preferences for treatments and services using a smaller number of scenarios extracted from a larger pool of choices ,87,88,89Some of the limitations of the CA methods are due to the lack of validated quality assessment tools for CA studies and lack of consensus on appropriate sample sizes ,3,4. FurTo the best of our knowledge, this is the first article to report the trend of CA publications and citations over the past 70 years and the increase in its popularity based on the amount of published literature. This article takes a well-defined, rich, and clear approach to the discussion of CA. It provides a summary of the very large and wealthy literature describing CA methods. The narrative nature of this article is based on a comprehensive search of the literature and utilized several databases. However, the narrative nature of the discussion could be subjective and open to different interpretations. Therefore, we recommend that the results of this article must be interpreted in line with its limitations. The results in relation to the CA trend over the past 70 years are not based on a comprehensive bibliometric analysis in terms of visualization. Nonetheless, it is based on a comprehensive search of WoSCC databases to identify the growth in CA publications.The popularity of CA in healthcare has been increasing and its use in this setting is gradually competing with its use in business and marketing research. CA is a useful method for eliciting patients’ preferences and WTP. However, there are some limitations in the available CA literature, specifically regarding the appropriate sample size, quality assessment tool, and the validity of CA. This highlights the need for researchers from different fields that use CA methods to come together and develop tools to address these limitations.


To investigate the clinical application of microsurgery using the cerebellar medulla fissure approach in severe ventricular hemorrhage with casting of the fourth ventricle and its effect on neurological recovery.  A total of 80 patients with severe intraventricular hemorrhage accompanied by casting and dilation of the fourth ventricle who were admitted to the neurosurgery department between July 2019 and December 2020 were randomly divided into an observation group and a control group, with 40 patients in each group. The drainage tube extubation time and length of hospital stay of the two groups were compared. The 3-day hematoma clearance of the two groups was observed. Postoperative consciousness was evaluated by GCS, and the patients' recovery was evaluated by GOS at three months. The activities of daily living (ADL) scores of the two groups were compared to evaluate patients' postoperative self-care ability. The incidence of postoperative complications in the two groups was collected. Independent risk factors for poor prognosis were analyzed by logistics regression.  The postoperative hospitalization time and the drainage tube extubation time in the observation group were significantly lower than those in the control group. The ratio of hematoma clearance ≥90% in the observation group was significantly higher than that of the control group. Postoperative GCS scores and GOS scores in the observation group were significantly higher than those of the control group. The rate of postoperative complications in the observation group was significantly lower than that of the control group. The rate of good ADL grading in the observation group was significantly higher than that in the control group. Age and surgical method were independent risk factors for poor prognosis.  Microsurgery using the cerebellar medulla fissure approach can effectively improve the condition of severe ventricular hemorrhage with casting of the fourth ventricle and promote the recovery of patients' neurological function. Intracerebral hemorrhage is a relatively common but extremely dangerous disease in clinical practice. In many patients, spontaneous intracerebral hemorrhage is caused by nontraumatic factors, and their mortality and disability rates are extremely high –3. If anIn patients with ventricular hemorrhage, ventricular casts tend to form, especially in patients with blood clots in the third and fourth ventricles; these patients develop blockage of cerebrospinal fluid circulation and compression of the brainstem , leadingAt present, the commonly used clinical treatment is a ventricular puncture and an injection of urokinase to dissolve and drain the hematoma or even lumbar cistern drainage in severe patients , 9. HoweTherefore, in this study, microsurgery was performed on patients with severe ventricular hemorrhage accompanied by casting of the fourth ventricle using the cerebellar medulla fissure approach to observe the short- and long-term efficacy of this approach.A total of 80 patients with severe intraventricular hemorrhage accompanied by casting and dilation of the fourth ventricle who were admitted to the neurosurgery department between July 2019 and December 2020 were randomly divided into an observation and a control group, with 40 cases in each group. The control group consisted of 23 males and 17 females (mean age: 58.54 ± 7.31) years, while the observation group consisted of 25 males and 15 females (mean age: 58.19 ± 8.73) years. The control group was treated with traditional ventricular puncture and drainage, urokinase lysis, and lumbar cistern drainage. The observation group underwent ventricular puncture and drainage, urokinase lysis, and removal of hematoma in the fourth ventricle through cerebellomedullary fissure approach. The study followed the Declaration of Helsinki and was approved by the ethics committee of our hospital. Both patients and their families were informed about the study and provided their written consent to participate in the study.Inclusion criteria were as follows: onset time <24 h; age >18; plain CT scan showing bleeding into the ventricle, with parenchymal bleeding <30 ml and a dilated hematoma in the fourth ventricle .Exclusion criteria were as follows: patients with secondary cerebral hemorrhage due to arteriovenous malformation, ruptured intracranial aneurysm, craniocerebral injury, brain tumor, or hemorrhagic infarction; patients who did not meet the surgical indications; patients with anticoagulation-related cerebral hemorrhage; patients who refused to follow up for clinical evaluation after discharge; severe hepatic and renal insufficiency; pregnant or lactating women with other malignant tumors.The control group received traditional ventricle puncture drainage plus urokinase lysis plus lumbar cistern drainage. Observation group used urokinase dissolution ventricular puncture and drainage plus the fourth ventricle cerebellomedullary fissure drainage to remove the hematoma. In the prone position of the patient, an incision was made in the middle of the posterior occipital region, and the foramen magnum was opened . The dura mater was cut in a Y shape and suspended to the upper and both sides. The hematoma in the cerebellar parenchyma was removed under the microscope, and the structures such as bilateral cerebellar hemispheres, vermis, cerebellar tonsil, medulla oblongata, and posterior inferior cerebellar artery were exposed. Cerebrospinal fluid was released from the arachnoid membrane in the greater occipital pool under the microscope. The arachnoid membranes around the cerebellomedullary fissure and cerebellomedullary pool were sharply separated, and the bilateral vermis tonsil space and medullary tonsil space were separated, so that the mobility of cerebellar tonsil was increased. The choroid was cut along the center and the border of the membranous medullary sail up to the upper margin of the lower medullary sail. The choroidal zone was cut from the latch toward the lateral recess, or it could be expanded to the posterior edge of the lateral recess and the lateral margin of the lower medullary sail. The cerebellar tonsil and vermis were retracted and fixed sideward and upward, and the choroid and inferior medullary sail were cut open to fully expose the bottom of the fourth ventricle. During the operation, the mesencephalic aqueduct was explored, and the hematoma was suctioned out without contact. No. 8 ventricular drainage tube was placed in the mesencephalic aqueduct, and the ventricular system was rinsed and dredged with warm normal saline. During the operation, the bleeding was stopped completely, and the fourth ventricle drainage tube was retained. The dura mater was tightly sutured, layer by layer until reaching the scalp. The epidural drainage tube was also retained. Postoperative antibiotics were routinely used to prevent infection, and oxygen inhalation, hemostasis, dehydration, and antihypertensive treatment were given. Meanwhile, nasogastric feeding or intravenous nutrition support was given to maintain the water and electrolyte balance. After the operation, the control group and the observation group received the same drugs and other treatments, including routine ECG and intracranial pressure monitoring, oxygen inhalation, dehydration to reduce intracranial pressure, nutrition of brain cells, prevention and treatment of rebleeding, drugs to relieve cerebral vasospasm, and active prevention and treatment of various complications and symptoms.The drainage tube extubation time and length of hospital stay for the two groups were compared. Twenty-four hours after surgery, a head CT was performed to observe the 3-day hematoma clearance rate. The 3-day hematoma clearance rate = (preoperative hematoma volume − postoperative hematoma volume)/preoperative hematoma volume × 100%. Postoperative consciousness was evaluated by GCS score, and the patients' recovery was evaluated by GOS score at three months . Patientt-test was used for their comparison between groups. Multivariate analysis adopts multiple Logistic regression model. P < 0.05 indicates that the difference is statistically significant.The results of this experiment were statistically analyzed by SPSS 20.0 . Count data were expressed by (rate), and chi-square test was used for their comparison between groups. Measurement data were expressed by (mean ± standard deviation), and A comparison of the clinical data of the two groups revealed no statistical difference between the two groups in terms of gender, age, time of onset, bleeding site, grab score, previous medical history, GCS score, coma, and intraventricular hemorrhage, as shown in A comparison of the operation indications of the two groups revealed that the drainage tube extubation time and length of hospital stay of the observation group were significantly lower than those of the control group, and the difference is statistically significant, as shown in A comparison of the 3-day hematoma clearance rate of the two groups revealed that the rate of patients with a 3-day hematoma clearance rate ≥ of 90% in the observation group was significantly higher than that in the control group, and the difference is statistically significant, as shown in The postoperative consciousness of the two groups was evaluated by postoperative GCS scores. It was found that the postoperative GCS scores of the observation group were significantly higher than those of the control group. The postoperative recovery of the two groups was evaluated by the GOS score after three months. It was found that the GOS score of the observation group was significantly higher than that of the control group, and the difference is statistically significant, as shown in The postoperative self-care ability of the patients was evaluated by ADL score. It was found that the rate of a “good” classification for patients in the observation group was significantly higher than that of the control group. The difference was statistically significant, as shown in A comparison of the postoperative complications of the two groups, including hydrocephalus, pulmonary infection, intracranial infection, and gastrointestinal bleeding, revealed that the incidence of complications in the observation group was significantly lower than that in the control group, as shown in The patients were divided into a ‘good prognosis group' and ‘poor prognosis group' according to their ADL score. The clinical data of the two groups were included in the univariate analysis . StatistThe development of ventricular casting caused by ventricular hemorrhage is very fast, the prognosis of patients is often poor, and the disability rate is very high . TherefoThe lumbar cistern puncture and drainage plus urokinase lysis treatment used in the past can reduce the compression on the brainstem, reduce brain edema, and release intracranial hypertension to a certain extent, but it takes one to two days to remove the hematoma in the fourth ventricle, which will result in serious damage to the patient's brainstem . At the The cerebellomedullary fissure is a natural physiological fissure in the brain that is located before the cerebellar vermis node and cerebellar vermis sag. This microsurgery approach does not require that the lower cerebellar vermis be cut to obtain access to the operation field and to open the fourth ventricular floor. Thus, this approach can be used to remove a hematoma without damaging normal brain tissue . The hemThis study has some limitations. First, the cerebellomedullary fissure microsurgery approach requires familiarity with the anatomical characteristics around the fourth ventricle. Second, a variety of neuroelectrophysiological monitoring needs to be combined during the operation to monitor the blood supply and brainstem function of patients. Therefore, the operation site needs to be adjusted .In conclusion, the cerebellomedullary fissure microsurgery approach can effectively improve the condition of severe intraventricular hemorrhage with casting of the fourth ventricle and promote the recovery of neurological function.


This paper compares the partnership arrangements of Turkish and Ethnic German immigrants , the two largest migrant groups in Germany, and native Germans. Most existing analyses of migrants' partnerships focus on intermarriage, marriage formation, or union dissolution. We know only a little, however, about the prevalence of non-marital living arrangements. Given that single person households and cohabitation are widespread phenomena mainly in post-materialist societies, analyzing whether immigrants engage in these behaviors sheds light on potential adaptation processes. The analyses are based on the German Microcensus of the years 2009 and 2013, with a focus on adults in the 18–40 age group. First, we present descriptive findings on the prevalence of partnership arrangements of immigrants and native Germans. Second, we estimate cross-sectional regressions with the partnership arrangement as the outcome variable in order to control for compositional differences between immigrant groups with respect to education. Our results show that while the vast majority of first-generation immigrants are married, the share of married natives is considerably smaller. Living in an independent household without a partner and cohabitation are rare phenomena among immigrants. By contrast, about one in seven natives is cohabiting and more than one quarter is living in an independent household without a partner. The most prevalent partnership living arrangement of the Turkish second generation is living in the parental household without a partner. These results are robust after controlling for education, age, and year in the multiple regression analysis. International migration is an event that affects every facet of a migrant's life. While many studies in Germany and European countries have focused on the socio-economic sphere, investigating migrants' educational success Kristen, , labor mThis study aims to identify the partnership living arrangements of Turkish migrants, Ethnic German migrants , and native Germans. In the first step, we compare the prevalence of partnership living arrangements  across immigrant groups. Second, we examine whether compositional effects with regard to education exist. We chose to focus on Ethnic German migrants and Turkish migrants because they represent the two largest immigrant groups in Germany. Moreover, the partnership behaviors in Turkey and in the origin countries of Ethnic Germans differ significantly from those in Germany, and such differences enable us to identify potential adaptation processes. Unfortunately, to our knowledge, there is no longitudinal dataset that is large enough to analyse the partnership transitions of different immigrant groups in GermanyIn the following, we provide a brief overview of the immigration context of Turkish and Ethnic German immigrants, and we discuss theoretical arguments and prior research about immigrants' partnership decisions. The rest of the paper is devoted to the empirical analyses.We focus our study on Turkish and Ethnic German migrants, as they represent the two largest groups of migrants in Germany, respectively making up 13.5%  and 12.5%  of the country's first- and second-generation immigrants . In these countries, Ethnic German communities had existed for many decades. After the collapse of the Soviet Union in the 1990s, a massive wave of migration to Germany took place. Being recognized as an Ethnic German immigrant guarantees full German citizenship Hensen, . The migsocialization hypothesis explains why differences in partnership behaviors between immigrants and natives in the country of destination might persist. Individuals socialized in countries with more traditional family values than Germany—such as Turkey  because eastern and western Germans still differ in their partnership behaviors  living without a partner in an independent household ; (2) living without a partner in the parental household; (3) living with a partner in a shared household without being married (cohabiting); and (4) living as a married couple in a shared household (married). Categories 1 and 2 include singles, but also individuals in living apart together relationships, as the partnership status in the Microcensus does not refer to partners outside of the household. Categories 3 and 4 includes individuals that live with their partner in their parents' home.In a first step, we report the percentage of partnership arrangements in each immigrant group. In a second step, we estimate multinomial logistic regressions. This allows us to account for potential composition effects. The independent variables included in the multiple regression analysis are age (as a continuous covariate), education , and a year dummy (2009 and 2013). Our first research question refers to the prevalence of partnership arrangements by immigrant status. The second aim of our analysis is to assess whether the compositional differences account for variations in partnership arrangements across immigrant groups. In addition to age, education might be associated with partnership choices. We estimate multiple multinomial regressions for men and women. Because the interpretation of the parameters of a multinomial logit model is not straightforward, we present the average marginal effects (AME). The average marginal effect is the mean of the marginal effects for each combination of covariates in the dataset. It represents the average change in the probability of seeing a specific outcome when we alter the respective independent variable from the reference to a different category, based on our sample. The results displayed in For the control variables, the results are largely in line with the literature. Individuals who are enrolled in education are less likely to be married or cohabiting than individuals with a vocational degree. This is also the case for women with a university degree, whereas men with university education do not differ in their likelihood of being married from those with a vocational degree. Highly educated individuals are more likely to cohabit. The AME of having no degree shows an insignificant association with marriage for women, but a significantly negative association for men. For age, the strongest associations are found for marriage and living in the parental home: The older a person is, the more likely s/he is to be married, and the less likely s/he is to be living without a partner in the parental household. There seems to be a slight  shift in partnership patterns over time, with the probability of living in a marital union being lower and the probability of living in an independent household without a partner being higher in 2013 than in 2009.Partnership living arrangements are an integral part of the family formation process, and thus greatly affect the lives of adult migrants and natives alike. The findings of this research suggest that these arrangements differ substantially between migrant and native adults in Germany. Marriage is by far the most common partnership form among the Turkish first generation, as well as among Ethnic German immigrants in the 18–40 age group. Among second-generation Turkish immigrants, the most prevalent partnership arrangements are “no partner, living in the parental household” and “married”. Cohabitation seems to be unacceptable in all three immigrant groups, whereas it is a common, albeit infrequent, arrangement among native Germans . Our multiple regression results indicate that these patterns can be explained by differences in educational attainment between migrants and natives to a very small extent only.Clearly, the higher prevalence of marriage among immigrants is associated with their lower mean age at marriage. The mean age at marriage in Germany is 32.1 years for women and 34.6 years for men (Destatis, Another reason for the high prevalence of marriage among Turkish and Ethnic German immigrants is more practical. The immigration of individuals from outside the EU is legally restricted, but the availability of family reunification visas facilitates the migration of the spouses of EU residents, and allows married couples to live together in Germany (Schroedter, The major weakness of the present research is related to the limits of the analyzed data, the German Microcensus. First, the information collected in the survey are very basic. In order to explain differences in partnership living arrangements between immigrant groups and generations, information about the partnership context at time of migration, religion, attitudes, and reasons for immigration is needed. The living arrangements of adults may also depend on factors such as the labor, housing market, and economic conditions; the decisions of peers; as well as norms and cultural expectations (Aassve et al., The datasets generated for this study will not be made publicly available because the German Microcensus is only accessible for registered users.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Despite public health interventions to control adolescent fertility, it remains high in sub-Saharan Africa. Ghana is one of the countries in sub-Saharan Africa with the highest adolescent fertility rates. We examined the trends and socio-economic and geographical patterns of disparities in adolescent fertility in Ghana from 1993 to 2014.Using the World Health Organization’s (WHO) Health Equity Assessment Toolkit (HEAT) software, data from the 1993–2014 Ghana Demographic and Health surveys were analyzed. First, we disaggregated adolescent fertility rates (AFR) by four equity stratifiers: wealth index, education, residence and region. Second, we measured the inequality through summary measures, namely Difference (D), Population Attributable Risk (PAR), Ratio (R) and Population Attributable Fraction (PAF). A 95 % confidence interval was constructed for point estimates to measure statistical significance.We observed substantial absolute and relative wealth-driven inequality in AFR  and  respectively in favour of the economically advantaged subpopulations. We found significant absolute  and relative  education-based inequality in AFR, with higher burden of AFR among disadvantaged subpopulations . The Ratio measure  indicates huge relative pro-urban disparities in AFR with over time increasing pattern. Our results also show absolute  and relative  inequality in AFR across subnational region, between 2003 and 2014. For example, in the 2014 survey, the PAR measure  and the PAF measure  indicate substantial absolute and relative regional inequality.This study has indicated the existence of inequality in adolescent fertility rate in Ghana, with higher ferlitiy rates among adolescent girls who are poor, uneducated, rural residents and those living in regions such as Northern, Brong Ahafo, and Central region, with increasing disparity over the time period of the study. There is the need for policy interventions that target adolescent girls residing in the rural areas and those in the low socioeconomic subgroups to enable the country to avert the high maternal/newborn morbidity and mortality usually associated with adolescent childbearing. Globally, demographic change has been a public health issue over the past few years . AdolescIn sub-Saharan Africa, adolescent fertility continues to be high despite the advancement of sexual and reproductive healthcare services to control fertility rate . AdolescDespite public health interventions to control adolescent fertility, it remains high in sub-Saharan Africa unlike other developing regions where it has significantly declined . The AFR2  * 100. For binary dimensions like residence, “D” is calculated as the difference between the subgroup with the highest estimate  and the subgroup with the lowest estimate (urban), regardless of the indicator type. For ordered dimensions like wealth and education, it is the difference between the most-disadvantaged subgroup and the most advantaged subgroup. For binary dimensions like residence, “R” is calculated as the ratio between the subgroup with the highest estimate  and the subgroup with the lowest estimate (urban), regardless of the indicator type. For ordered dimensions like wealth and education, it is the ratio between the most-disadvantaged subgroup and the most advantaged subgroup. In the absence of inequality, D and R become zero and one, respectively. Point estimates were calculated and presented with corresponding 95 % Confidence Intervals. To examine whether AFR shows statistically significant disparities across the sub-groups of each equity stratifier, and to determine whether or not the inequality changed with time, we computed 95 % Confidence Intervals (CI) around point estimates of each measure for each survey. For all inequality measures other than R, the lower and upper bounds of the CI must not include zero to interpret that inequality exists. For R, the interval should not include one. We assessed the trend of inequality for each summary measure by referring to the CI for the different survey years. When the CIs do not overlap, it implies that there is statistically significant difference between the two CIs. If the CIs overlap, then no inequality exists.Table We observed substantial absolute and relative wealth-driven inequality in AFR from 1993 to 2014 both by simple  and complex  measures. For instance, in the 2014 survey, the PAR measure  and the PAF measure  respectively, showed significant absolute and relative economic-related inequality in favour of the economically advantaged subpopulations. In terms of educational level, we found significant absolute  and relative  education-based inequality in AFR, with higher burden of AFR among disadvantaged subpopulations . The pattern was replicated in all the survey rounds based on simple measures , while complex measures  suggested persistent disparities to the disadvantage of adolescent girls with no formal education.We also found absolute and relative urban-rural inequality in AFR from 1993 to 2014 both by simple  and complex  measures with an increasing pattern in magnitude of disparity over the years. For instance, in 2014, the R measure  indicated high burden of AFR to the disadvantage of rural girls with an increasing pattern during the period under study. Our finding also shows absolute  and relative  inequality in AFR across subnational region, between 2003 and 2014. For example, in 2014 survey, the PAR  and the PAF measures  indicated substantial absolute and relative regional inequality . It is worth nothing that AFR is considered an adverse health outcome in the Health Equity Assessment Toolkit (HEAT) analysis . This imThe study revealed that there has been significant improvement in the prevalence of AFR in Ghana from 1993 to 2014; reducing dramatically from 118.7 % to 1993 to 73.3 % in 2014. Thus, on a prima facie basis, it can be observed that Ghana has seen consistent reduction in the prevalence of AFR throughout the 16-years period, except for the period between 2008 and 2014 where the rate of adolescent fertility increased marginally from 69.7 to 73.3 %. This seemingly decreasing trend in the prevalence of AFR in Ghana over the years may be attributed to the steady increase of modern contraceptives from 1998 to 2008 . Also, tOur findings also suggest that there is inequality with regards to the dimension of wealth or economic status. From the results, it can be observed that the prevalence of AFR was low among those in the richest wealth quintile compared to those in the poorest wealth quintile in 1998. Moreover, the study showed both significant absolute and relative economic related inequality in favour of the economically advantaged subpopulations. This finding corroborates previous body of knowledge that posit that AFR is low among women in the richest wealth quintile –18. For With respect to education, the contribution of educational inequality to AFR is seen in both the absolute  and relative inequalities . This implies that education plays a significant role in AFR in Ghana. Consistent with extant literature, the results of our study suggest that disadvantaged sub populations  suffered a higer burden of AFR compared to thier counterparts with secondary or higher education. Our finding falls in line with the postulation by Pons-Duran, Lucas, et al.  and AsamOur study also found absolute and relative urban-rural inequality in AFR from 1993 to 2014, demonstrating pro-rural disparities  in AFR with over time increasing pattern. This is an indication that Ghana has a long way to go to bridge the inequalities in the rural-urban dichotomy. This finding affirms several studies that have found that adolescents dwelling in urban areas tend to have lower AFR compared to their counterparts in the rural areas –24. One Besides the inequalities observed among subpopulations in education, wealth quintile and place of residence, our findings revealed that there was inequality in AFR across subnational region, between 2003 and 2014. This was evident in the PAR measure  and the PAF measure . There is no clear explanation for the inequalities across the subnational region. However, we can speculate that it has its roots deep-seated in the dynamics of each region. Greater Accra is known to be the most urbanized region [From policy standpoint, there is the need to demystify discourse of adolescent marriage and pregnancies at the community and household level so that adolescents will be well informed about the options available to them. From the cultural standpoint, parents should be admonished to have open discussion with the female adolescent about their sexual behaviours with special emphasis on disadvantaged subgroups such as those in the rural areas and low-income households. Moreover, public health professionals in the Ghana Health Service can use the information from this study as a guide in the formulation and implementation of policies to address the socioeconomic and regional disparities in AFR in Ghana.The study has several strengths. First, to the best of our knowledge, this study is the first to examine socio-economic and geographical inequalities in AFR in Ghana from 1993 to 2014. Hence, the findings can be essential in guiding both policy and future research on adolescent fertility rates in this country. Secondly, the use of both simple and complex measures of inequality contributes to the quality of our results as the limitations of each group of measure is dealt with by the strengths of the others. Thirdly, by presenting the findings for each subgroup of the equity stratifiers, we provide a benchmark for the government to identify where attention is much needed in the midst of limited resources. Finally, using the WHO’s HEAT software for the analysis confirms the reliability of the findings. Nonetheless, there are some limitations that need to be acknowledged. In this study, the focus was on the description of the nature of AFR inequality in light of the recommended dimensions of health inequality. We recommend the use of decomposition analysis to assess factors that could explain the disparities in AFR across various dimensions of inequality observed in this study. Again, the study used secondary data and so the authors had no influence over the selection and measurement of the variables. Additionally, there is a possibility of under-estimating AFR in the surveys due to pregnancy terminations among adolescents. There are other sociocultural variations that were not considered in this paper such as ethnicity and religious affiliation which could affect AFR. Therefore, future studies on AFR can examine the inequality patterns by ethnicity or religious affiliation.This study has revealed the existence of inequalities in AFR in Ghana to the advantage of adolescent girls in better socioeconomic classes and who are located in urban settings, with increasing disparity over the time period of the study. Policy makers need to institute measures to reverse the trends in the disparities by targeting subgroups which are highly disadvantaged. There is the need for strategies and interventions that targets these marginalized subgroups to address the disparities in AFR so as to effectively and efficiently deal with the challenges of high maternal and newborn morbidity and mortality associated with adolescent childbearing. Emphasis should be given to adolescents in rural areas and those in lower socio-economic class.


Family policies and family support measures have been identified as having major implications for child well-being, particularly through their role in influencing parental and family resources, circumstances and behaviour. The official approach to family policies focuses on opportunities for families to balance their work and family duties and care for their children. This paper analyses the type of policies available in Montenegro compared to the European Union. Potentially, Montenegro will become an EU member state, thus it is important to take a look at Montenegrin practice, as children should have equal life chances and protection of their well-being. Having a solid legal framework per se does not necessarily result in significant positive outcomes, and this paper analyses whether children in Montenegro have the same opportunities for development, in the context of family policies, as their counterparts in the rest of Europe. The focus of the paper will be on the criteria that define family rights and obligations, eligibility, availability and use of family policies in Montenegro. Based on the specific measures and datasets examined, the analysis considers the degree to which a period of family policy investment in Montenegro has been accompanied by improvements in child well-being and family resources, and undertakes comparisons in these regards with EU-wide family policy and child well-being trends. The paper uses a welfare state theoretical approach, with the focus on social investment and relevant data on children’s well-being obtained from the Eurostat, the OECD and the official national statistics. Improving the well-being of children has deep and long-lasting benefits for societies. Researchers and policy makers alike have long investigated potential means of improving societal mechanisms aimed at children and families. This paper examines the advances made by Montenegro as a result of reforming its family policies. It does so by comparing these reforms, and their outcomes with wider EU trends and by considering the extent to which these changes in family policies go hand in hand with improvements in the well-being of children and families. As a recognised candidate for membership of the EU, Montenegro is progressively adopting family policies in accordance with EU standards and requirements. However, there is a pressing need for research investigating the extent to which reforms to family policy in Montenegro are in fact associated with improved conditions for children and families.This paper analyses Montenegro’s major family policy documents and focuses on those documents recognised as directly linked with children’s well-being, such as parental leave policies and early education policies, and on research that investigates the well-being of children and families. These are then compared nationally and to wider EU trends. Using a macro-level comparison approach, the living conditions of children and families in Montenegro are evaluated more broadly. This reveals potential trends that may hinder, or support, the well-being of children and families.There has been much theoretical work carried out with the aim of developing family policies. Reflecting the various social changes that have taken place over preceding decades, a wide variety of different approaches to family policies have emerged. Recent work on family policy has investigated changing childbearing and partnership trends, the effects of different household structures on childhood well-being, the relationship between well-being, economic activity and socio-economic trends, and the consequences of an ageing society . Given tIn what follows, family policies are taken to be “policies associated with families with children”, and as policies that seek to promote the functionality and well-being of families with children . In KameAlthough family households, parents’ circumstances and the well-being of children are the main focus of this paper’s analysis, ‘family’ is recognised as having multiple meanings and applications across different European contexts. It is important to recognise a diversity of family household formations, relationships and practices within and across countries, as well as the diverse ways in which the family lives of children and parents operate beyond and across households. Furthermore, this paper takes a critical perspective that challenges the inequalities and risks associated with family constructs and dynamics. The analysis presented here has as one of its background commitments that children’s rights, gender equality and social justice are crucial and necessary family policy goals ,5.The family policies explored and analysed in this paper are those that exist at the national level, created by national legislation and funded by a state’s central government. This is important to emphasize, as policy can also be established at subnational or supranational level and even at the level of individual private companies and organisations . AdditioThe theoretical approach used in this paper is welfare state theory, with a particular focus on the social investment paradigm. This is a future-oriented approach which investigates the development of human capital and the opportunities for investing in citizens from the earliest age. The approach aims at prevention and preparation, developing proactive measures rather than acting after the fact . AccordiA study published by the OECD in 2009 demonstrates that family policies can have a positive impact on children’s well-being . The stuOther studies have produced similar results. Norwegian practice reveals the positive effects of universal preschool childcare and education on educational outcomes in high school and beyond, as well as on earnings ,10. BakeOne current debate is whether universal childcare for children older than three, offered in preschool education and care institutions, has an equally positive effect on all children. In other words, do all children benefit from this universal provision to the same extent or do outcomes vary depending on factors such as the economic status and welfare of parents, implying the need for a more targeted approach ,14,15? CJavornik  argues tFamilial and de-familial approaches both provide insights into the nature of caring obligations and the ways in which the design of a country’s welfare state reinforces one or the other ,19. The Normative assumptions about gender roles and the social organisation of care play a role in defining regulations dealing with parental leave and childcare services, a process referred to as policy conceptual logic . The speA child’s living conditions also influence the level of well-being and subsequent life opportunities. Poverty and lower family income may have a substantial negative impact on a child’s well-being. Additionally, the timing of poor or worsening living conditions has also been shown to be important, with the most negative effects being observed during a child’s preschool and early school years ,29,30,31The key materials reviewed and analysed in this paper are EU and OECD statistics, along with national and EU family policy documents and strategies. The paper reviews these official data and policy sources in order to evaluate recent reforms and trends in the particular case of Montenegro and compares these with prominent reforms and trends in the EU more widely. The EU and OECD statistics, drawn from Eurostat and the OECD family database, constitute the most comprehensive sources of official national statistics for European countries and provide the best basis for a comparative study. The paper also draws extensively on the European Union Statistics on Income and Living Conditions (EU-SILC), a major source of EU official data from 2003 onwards. This database provides longitudinal comparative national socio-economic data for EU member states, as well as for European countries that are not member states, covering multiple social and economic indicators and domains.It is important to recognise that these data sources at best indicate associations between national reforms and national trends. For the purpose of policy evaluation, these associations require further empirical investigation. Nevertheless, the data provide valuable statistics that reveal cross-national and regional European trends which have been subject to close attention and have led to quality improvements. These data sources, however, also have limitations. For example, the sources often rely on individual and household statistics and on units of analysis which can only provide a partial picture of family membership, resources and dynamics . The papFamily policies have long been recognised in Montenegro’s legal framework. The Family Law, the Labour Law and the Law on Social and Child Protection set out the major policies in this area and how they can be implemented. The Family Law prescribes parents’ responsibilities and their duty of care towards children. This law ensures that children’s rights are guaranteed and protected. The same Law provides the rights and well-being of children and a high level of protection, clearly defining the role of the parents and ensuring the necessary institutional support. Parents are legally recognised as their children’s guardians. Any type of discrimination against children is forbidden and public institutions are legally obliged to care for children when their family is unable to .The Labour Law and the Law on Social and Child Protection set out additional family policies as well as their availability and the criteria governing eligibility. The Labour Law ensures the provision of 365 days of parental leave, available for parents to use equally, of which 30 days are transferable . The LawA second aspect of Montenegro’s family policies aims at supporting parents’ labour market participation. The policies in question concern preschool education institutions and the country’s care infrastructure, and the availability, accessibility and affordability of these resources. The EU’s Work–Life Balance Directive for working parents and carers recognises this as a crucial element in the ability of parents to remain part of the labour market . Access However, this policy has resulted in an increase in the number of children enrolled without a corresponding increase in capacity, resulting in class sizes as large as 70 in cities and urban areas . This isChildren’s rights and the features that constitute an appropriate upbringing are recognised in the Montenegrin strategic framework. The current strategic framework includes the Strategy for Exercising the Rights of the Child 2019–2023, the Strategy for Early and Preschool Education in Montenegro 2016–2020, the Strategy for the Prevention and Protection of Children Against Violence 2017–2021, the Strategy for Employment and Human Resources Development 2016–2020, the Inclusive Education Strategy 2019–2025, the Strategy for the Development of the Social and Child Protection System from 2018 to 2022 and the National Strategy for Sustainable Development until 2030. The scope of this paper does not allow for detailed individual discussion of these strategies. Instead, considering the paper’s primary concern, they are analysed in the context of children and family policies.An analysis of the strategic framework reveals a lack of recognition of the importance of family policies in the context of children’s development and their well-being. Indeed, family policies are not even mentioned, other than in the National Strategy for Sustainable Development until 2030 . This stThe European Union has recognised the importance of family policies and has placed them high on its social policy agenda. The EU Pillar of Social Rights affirms a child’s right to have an affordable early childhood education and good quality care; it also affirms that children should be protected from poverty and should have equal opportunities, especially those from disadvantaged backgrounds. The EU Recommendation on Investing in Children also provides firm guidance and policy recommendations seeking to improve children’s well-being and their future opportunities by stressing the need to invest in their human capital from an early age . The RecA more recent and legally binding document, the Directive on Work–Life Balance for Parents and Carers , points These documents show the EU’s firm dedication to its long-term goals and reflect a careful approach to children and their development. Furthermore, the EU’s strategic planning includes a recognition of parents as an irreplaceable component of childhood development. Parents’ well-being is understood as a precondition for children’s well-being. This acts to reinforce the fact that family policies must be coordinated among all of the institutions which are part of the process.According to the EU-SILC data, the risk of poverty or social exclusion for the population as a whole was 30.5% in 2019, which is a decrease of 0.9% compared to the previous year . The risA comparison of living conditions in Montenegro with the EU reveals significantly higher rates of risk of poverty and social exclusion in Montenegro than in the majority of member states, as well as the EU averages. Compared to Montenegro, the risk of poverty and social exclusion (AROPE) was higher in 2019 in Bulgaria (32.8%) and Romania (31.2%), and similar in Greece (30%). However, the standard deviation for AROPE for the EU in 2019 is 5.25, which reveals strikingly large differences among countries. The risk for children up to 17 years of age was also higher in Montenegro in 2019 when compared to the EU average (23.4%). It was also higher than in any EU member state, the closest being Romania (35.8%), Bulgaria (34.1%), Greece (30.5%) and Spain (30.3%) . SimilarSingle-parent families in 2019 faced a higher risk of poverty or social exclusion in Montenegro (58.3%) than the EU average (43%) . The samThe level of participation of children aged between 4 and 6 in preschool education and care institutions has steadily increased in Montenegro since 2015. In 2015 a total of 16,972 children were enrolled, compared to 21,663 children in 2018 ,46. ThisIn Montenegro, the average class size in 2019 was 29.7, with an average of 31.6 pupils in public institutions and 13.5 in private institutions. The pupil–teacher ratio was 16.6 on average, with 16.8 in public institutions and 13.8 in private institutions . More thWhen considering the matter of which parent acts as the primary caretaker and therefore takes parental leave, we can note that the number of fathers taking paternal leave more than doubled between 2018 and 2019 from 203 to 421 . HoweverThis low level of parental leave uptake by fathers, which can be safely assumed to have been significantly lower in 2015, can be compared with available data for the EU for 2015. When this comparison is carried out, the level is revealed to be well below the EU average of around 10% . Once agThe social protection budget in Montenegro has decreased in relative terms , from 17The OECD data reveals large differences in replacement parental pay, when measured as a percentage of previous earnings . The datAn overview of the Montenegrin implementation of family policies reveals a solid legal framework which is not reflected in similarly positive outcomes. Nor, it must be admitted, is there a strategic recognition of family policies. In comparison with EU member states, Montenegro is lagging behind in practice. This is despite, as could be seen in the previous section, the more favourable legal requirements and conditions with regard to at least some family policies.The analysis carried out in the previous section demonstrated significantly higher risks for all of the social groups relevant for our purposes, particularly for single-parent families. This is all the more pressing given that single-parent families are not recognised in the Montenegrin strategic framework as being vulnerable or at a higher level of risk. Data shows that the yearly number of divorces has steadily increased between 2016 and 2019, from 703 to 841 . This poThe ample provision of maternity leave in Montenegro, especially in comparison to EU member states, provides an opportunity for women to take long and well-paid breaks from their work. However, this provision also leaves unanswered questions concerning women’s future prospects and long-term work opportunities, which may be negatively impacted by a long absence from work. Shortening the statutory period of leave, however, is unlikely to have a positive impact on the well-being of either women or, especially, children. Such a change would raise concerns about the quality of care that mothers are able to provide and may lead to periods of leave being taken by other means. Single parents face an additional risk as they need to successfully combine work and sole caring responsibilities. The provision of long periods of parental leave can be expected to have a positive impact on children’s well-being.The 2019 Eurydice report includes Montenegro in its comparison of early childhood education and care (ECEC) standards and aligns Montenegro with the highest ranked countries in the EU. One criterion the report uses to assess countries is the educational requirements placed on staff working with children. Montenegrin laws require staff to have a bachelor’s degree or higher, which is the case in one third of the countries included in the report . MonteneNevertheless, keeping in mind the number of children in classrooms, as well as inadequate knowledge and skills testing of practitioners , the actEducational outcomes can also be understood as consequences of a high-quality family policies framework. For the purpose of this paper, PISA test results are considered. With regards to average test results, in 2018 Montenegro was placed 54th out of 77 countries, with an average score of 422 . It was The use of preschool education and care in Montenegro has only increased significantly in the last decade or so, a consequence of the familial policy approach taken during the previous period. During this period, families were expected to care for children at least until the age of 3, or a year before the child began attending school. Montenegro also has a long history of men being expected to be their family’s breadwinner. This has started to change, especially in the last two decades, bringing Montenegro in line with most of the countries that belong to what Esping Andersen calls the conservative model of the welfare state ,58. The A comparatively lower level of paternal leave uptake, together with a lower level of childcare participation, jointly imply that women carry a greater childcare burden in Montenegro than women in EU member states. In the long term, this may create pressures on the economic stability of families, subsequently endangering children’s equal access to opportunities. Lingering questions over the quality of childcare, as a result of overcrowded classes and practitioners being insufficiently knowledgeable and poorly tested, provide additional pressure on families, especially on single parents.The data on the social protection budget shows that Montenegro spends less on cash and in-kind benefits related to households than the average EU member state . AlthougThese conclusions demonstrate the need to further investigate the systemic causes of the poor outcomes of what is currently a very de-familial policy approach. This is an approach which is supportive for mothers and creates positive conditions for childcare enrolment. However, the case of Montenegro reveals that the well-being of children requires the careful coordination of different policies, including, but moving beyond, family policies. A lack of strategic recognition of family policies strongly indicates that Montenegro lacks a future-oriented approach. This would be one that takes advantage of the cumulative positive outcomes of family policies. Instead, Montenegro has individual policies which serve their purpose of providing rights to citizens but fail to create conditions in which these citizens can prosper. A longitudinal study on educational and occupational attainment would allow for more nuanced results and would provide further, and more detailed, insights.Montenegro’s status as a merely prospective EU member may leave those citizens who are now children with significantly lower opportunities for a prosperous life. This is because their human capital has not been optimally developed. Montenegrin children live in worse social conditions than children in the EU. As a result of this, as well as other negative outcomes such as a worse quality of care in preschool educational institutions, their well-being is lower than those living in EU member states.Single-parent families are facing an increased risk of poverty and social exclusion. Together with the lower quality of care that may result from increased class sizes in preschool education institutions, the well-being of these children is severely endangered. PISA test results for Montenegro’s current high school students reinforce the need to address these issues by planning policies in accordance with the other relevant policy areas. Furthermore, policies need to be planned in a way that their joint outcome does not undermine the intended positive consequences of any individual policy. Vulnerable groups must be clearly defined, as must those policies which aim at promoting their well-being. In the context of family policies, this means special attention must be paid to policies aimed at single parents.This paper examined family policies in Montenegro and compared them with those in the European Union. It has been demonstrated that the Montenegrin legal framework takes a positive approach to family policies with regards to the duration of parental leave, as well as to the replacement rate of parental pay, which is higher than the EU average. Furthermore, access to a preschool education and to care institutions is provided to all children, allowing parents an opportunity to work. However, evaluation of the data shows that the relevant indicators lag behind the positive intent behind the legal framework. As a result, when compared to those living in EU member states, children and parents in Montenegro enjoy significantly lower living standards and face a higher risk of poverty and social exclusion.Despite the favourable conditions created by generous parental leave and the universal provision of preschool education and care, single-parent families face a higher risk of poverty and social exclusion. The analysis carried out here demonstrates that children in Montenegro have lower levels of educational attainment and, together with the higher risks they face, that their well-being is placed under significantly more strain than that of their EU counterparts. Similarly, the human capital of Montenegrin children may not be as fully developed as that of children in the EU. These conclusions demonstrate the need to reconsider the implementation of these policies and the necessity of further policy coordination. Successfully doing so has the potential of bringing Montenegro in line with the EU and decreasing the level of risk faced by its children.


Introduction: Biosimilar medicines are considered promising alternatives to new biologicals with high price tags. The extent of savings resulting from biosimilar use depends on their price and uptake, which are largely shaped by pricing, reimbursement, and demand-side policies. This article informs about different policy measures employed by European countries to design the biologicals market and explores potential savings from the increased use of biosimilar medicines in Germany.Methods: Policy measures that target the price and uptake of biosimilar medicines were identified based on a prefilled questionnaire survey with public authorities in 16 European countries, who were the members of the Pharmaceutical Pricing and Reimbursement Information network (July 2020). Potential savings that could have been generated in Germany if different measures identified in the surveyed countries had been implemented were calculated for six publicly funded biological molecules. Price data of the Pharma Price Information service and German consumption data for 2018 were used for the calculation of five scenarios.Results: Several countries use a price link policy, setting the biosimilar price as a percentage of the price of the reference biological. Also lowering the price of the reference biological upon market entry of a biosimilar is less frequently used. While tendering of biosimilar medicines in the inpatient setting is the norm, it is rarely employed for biosimilars in outpatient use. Reference price systems and INN prescribing of medicines are the commonly used policy measures in the off-patent market, but some countries define exemptions for biologicals. Substituting biosimilars at the pharmacy level is rather an exception. Potential savings in Germany ranged from 5% (simple price link) to 55% (prices at the level of other countries) for the six studied molecules.Conclusion: Despite some differences, there are discernible tendencies across European countries with regard to their applications of certain policy measures targeting the price and uptake of biosimilar medicines. The potential for savings of some of these policies was clearly demonstrated. Monitoring and evaluation of these rather recent measures is key for obtaining a more comprehensive picture of their impact. Payers have been concerned with discussions on high-priced medicines for years, regardless of their countries’ ability to pay; these discussions have been fueled by the perception that the expenditures on a number of very expensive medicines threaten the financial sustainability of publicly funded health systems. In some countries, new high-priced, on-patent medicines have contributed to increasing pharmaceutical expenditures in recent years .Biologicals  are widely used in the treatment of chronic conditions, such as diabetes and autoimmune disorders, as well as cancers, and they often carry high price tags. By offering more affordable alternatives, biosimilar medicines are considered a promising solution to very high-priced biologicals . A biosiHowever, in contrast to marketing authorization, pricing and reimbursement as well as any measures to steer the use of medicines (including enhancing the uptake of generics and biosimilars) are national competences of the EU Member States. The respective policies lead to differences both in the prices and the extent of use of biosimilars across countries , both ofIn recent years, the savings potential for public budget resulting from biosimilar use has been shown: Tendering for infliximab in Norway in 2015 led to the procurement of biosimilar remsima at a price 72% below the official list price of the reference medicine ; biosimiIn addition to the effect of pricing and procurement, demand-side measures also play a significant role, inter alia by increasing knowledge about biosimilar medicines, fostering trust and therefore the tendency to use them among patients, prescribers, and dispensers . One sucWhile the saving potentials of biosimilar use have been established by a number of example cases, an analysis of achievable savings from biosimilar use as a result of specific policy options is lacking.This article has two aims: on the one hand, to provide an updated overview of the different policy measures employed by governments in European countries to shape the biologicals market; and on the other hand, to explore the potential savings resulting from the use of biosimilar medicines under different scenarios of such measures, taking the German pharmaceutical market as an example.To obtain detailed information on measures regarding price-setting and procurement mechanisms for biosimilars (and generics as comparators) and demand-side measures targeting prescribing doctors and dispensing pharmacists, a survey was carried out among representatives of public authorities responsible for medicines policies in the countries of the study.Sixteen European countries were selected in this study. They include Austria (AT), Belgium (BE), the Czech Republic (CZ), Denmark (DK), Finland (FI), France (FR), Germany (DE), Ireland (IE), Italy (IT), the Netherlands (NL), Norway (NO), Portugal (PT), Slovakia (SK), Spain (ES), Sweden (SE), and the United Kingdom . The study was done from a German perspective, and all other countries except Norway are used as a secondary criterion during price negotiations between payers and manufacturers in Germany. Norway was included because it is known for generating savings from biosimilar medicines . The samIn July 2020, the members of the Pharmaceutical Pricing and Reimbursement Information (PPRI) network were contacted and asked to validate prefilled information on policies applied for biosimilars and generics as of 2020 and to provide missing information. The PPRI network is operated by the Austrian National Public Health Institute  and comprises competent authorities for pricing and reimbursement of medicines in 51, mainly European, countries . The autWe examined potential savings for the German publicly funded market in 2018 that could have been achieved if different measures identified in the surveyed countries and targeting a) biosimilar prices and b) biosimilar uptake had been implemented and/or prices as observed in other countries were in place, using a sample of six biological active substances.We determined pharmaceutical expenditure for the medicines included in the sample, based on price data as of December 2018 and volume data from the German publicly funded market (only outpatient setting) for the year 2018. We calculated the expenditure for the different scenarios and compared the expenditure data of each hypothetical scenario to the baseline pharmaceutical expenditure to derive the savings potential.The sample included biologics for which the patent had expired and biosimilars have been brought to the markets of the study countries, as price data of biosimilars in other countries were needed for the calculation in some scenarios. For the selected active substances , a total of 20 medicines  were included in the sample see .The prices of the included products were obtained from the Pharma Price Information (PPI) service of GÖG, which provides price data of official sources in European countries. Ex-factory prices in Euro were used in the calculations, with conversion of data for non-Euro countries . For countries where the ex-factory prices were not available due to their policy framework , the PPI service provided ex-factory price data based on statutory wholesale prices and average wholesale margins. The German price data considered the mandatory manufacturer discount of 7% gross on the ex-factory price.Competent authorities filled out historical data gaps upon request where needed and possible. Out of the sixteen countries in the study sample, prices from Ireland and Portugal were not included in the scenario calculations .Consumption data for the included medicines (expressed as items dispensed) in the German publicly funded health system for 2018 were obtained from the AOK Research Institute (Wissenschaftliches Institut der AOK–WidO).Savings can be achieved by changes in price, structure, or volume of prescribed medicines see also . This woDetails on the methodology, including a step-by-step description of the calculations for each scenario, are provided in the Importantly, the calculations are meant to be illustrative, using Germany as an example to explore possible savings, and are not designed as a budget impact assessment. Given the novelty of several policy measures as well as the rather recent patent expiry for some biologicals (and consequently short period of market availability for some biosimilars), a budget impact assessment in accordance with the established methodological principles would not have been possible for all the policies surveyed and medicines analyzed in this study, and such an evaluation was not intended.The following subsections provide an overview of supply and demand-side policies that pricing and reimbursement authorities can use to set the price and increase market penetration of biosimilars in the sixteen studied countries as of July 2020. Supply-side policies concern pricing, procurement, and reimbursement mechanisms, while demand-side measures are targeted at health professionals. These policy measures and their design have been laid down in national legislation.When a new generic or biosimilar medicine is brought on the market and/or included into reimbursement, pricing authorities can set its price in relation to the price of the originator or reference medicine if the so-called price link policy has been set out in national legislation: in such cases, the price of a generic or biosimilar medicine has to be set at a certain percentage lower than the originator or reference medicine price. In some countries, price link regulations are also in place for the prices of subsequent generics or biosimilars, which are set based on the prices of generics or biosimilars already on the market. Sometimes, price link policies also include provisions that influence (i.e. reduce) the price of the originator or reference medicine upon generic or biosimilar market entry .In all the studied countries, tendering is used to procure biosimilars for the inpatient sector see . In mostA number of countries also use tendering (or tendering-like elements) to procure off-patent medicines, mostly generics, in the outpatient setting . A well-In the Danish outpatient sector, procurement for all reimbursable medicines including biosimilars is based on a tender-like model. Every two weeks, manufacturers have to report to the Danish Medicines Agency planned prices of all their products used in the outpatient sector. The lowest-priced products per substance are considered first choice and covered by the publicly funded health system for the period of the next two weeks. To ensure the availability of medicines, products with the second- and third-lowest price can be dispensed  in case of shortages. Manufacturers who cannot supply are removed from the price list for the tendering time period. Reporting and updating processes are supported by an IT system, which undertakes up to 1,500 updates per two-week period. To mitigate logistic challenges for community pharmacies, cooperation agreements exist with wholesalers and manufacturers, for instance regarding the return of non-dispensed products at the end of the two-week period .In Germany, discount contracts between individual payers (sickness funds) and manufacturers can be considered some sort of tendering for outpatient off-patent medicines. In return for granting discounts on their products, manufacturers can benefit from exclusive dispensing of their medicines. For biologic medicines, the variant of so-called open house contracts has been commonly used: a sickness fund offers to all competing suppliers of a substance a contract that prespecifies the discount rate. Any manufacturer of biosimilar or reference medicines willing to grant this discount rate can join the contract, without conducting any individual negotiations .Most of the countries included in the study have a reference price system in place, which groups products of the same active substance or therapeutically interchangeable medicines into clusters and defines a maximum reimbursement amount per cluster , thus indirectly regulating medicine prices .Reference price systems are in place in thirteen of the sixteen studied countries, and they vary in methodological terms, regarding how a) the clusters and b) the price benchmarks are determined. This also applies to biosimilars: some countries include biosimilars in the reference price system  and others do not see . Since 2One of the main policies that affects how physicians prescribe medicines is prescribing by International Non-proprietary Name (INN) instead of the trade name of the medicine. INN prescribing has been implemented in many countries, including most of this study , and some even mandate it . While mIn all the countries studied here, physicians are expected to prescribe rationally, and retain final decision-making power on therapeutic choices. Prescribing quotas are another measure used by a number of countries to steer the use of lower-priced medicines in the off-patent sector. These are predefined targets for the share of generics or biosimilars physicians are expected to observe when prescribing. In Belgium, quotas for “cheap” medicines vary by physician specialty . So-called cheap medicines include generics, biosimilars, and all originators and reference medicines with prices as low as those of generics or biosimilars . Until ABiosimilars can be prescribed to treatment-naïve patients, or a physician can change a patient’s treatment regimen from a reference medicine to a biosimilar or from one biosimilar to another . While all countries stress that final decision-making power rests with the prescribing clinician, switching is in general recommended, or at least not prohibited. Switching recommendations are largely bound to certain preconditions, such as shared decision-making and close monitoring. Most countries have published related guidelines, developed by the competent authorities and/or the medical profession see .One of the most important measures for the increased use of economical medicines is substitution at the pharmacy level. Generic substitution has become standard and is employed in all the studied countries except Austria and the United Kingdom . In contAs of 2020, biosimilar substitution is only permitted in the Czech Republic (though not recommended by practitioners). In Germany, a law passed in 2019 foresees the automatic substitution of biosimilars in pharmacies beginning in 2022, provided the Federal Joint Committee  has determined the interchangeability of the medicines in question and the prescribing physician has not explicitly excluded it. In France, the regulatory framework permitted the introduction of biosimilar substitution from 2014 on, under the condition that an implementing order detailing specific provisions would be passed by administrative courts, setting out the necessary requirements for building biosimilar groups and entering the biosimilars registry. However, this order has not been issued over the years, thus hindering actual implementation biosimilar substitution, and the Social Security Law of 2020 abolished biosimilar substitution completely .Financial incentives for dispensing biosimilars are not present in the sample of countries, with the exception of France, where pharmacy margins for biosimilars  are calculated based on the price of the reference medicine so as to not disadvantage pharmacists who dispense lower-priced interchangeable medicines.German statutory expenditure for the six included active substances , or the “baseline scenario” for this study, amounted to € 2,223.9 million in 2018. The largest shares were 36.5% for adalimumab, 20.6% for etanercept, and 15.3% for trastuzumab.The largest savings were achieved under scenario 1 (“European prices”), which considered official list prices of other countries within the sample. Savings in scenario 2 (“price link–biosimilars”), which assumed a 30% lower price for biosimilars compared to the reference biological, were the smallest among the five scenarios (4.8% change). A price link policy affecting both biosimilars and reference medicines upon biosimilar market entry  would triple these savings. Scenario 4 (“RPS–DE”) led to savings of € 401.5 million by assuming the inclusion of biosimilars in the clusters of the reference price system; also considering prices in other countries (scenario 5: “RPS–Europe”) for the calculation of the reference price more than doubled these savings. This scenario achieved the second largest savings compared to baseline.The aim of this contribution has been to contextualize different mechanisms for pricing and encouraging the use of biosimilars in European countries, and explore their implications for pharmaceutical expenditure. Previous studies have highlighted the dormant potential for savings from the use of biosimilars  and haveEarlier reviews  of policDespite the fact that price link policies seem to have some potential for savings (as demonstrated by scenario 2), not all the countries studied here apply them. A reduction in the reference medicine price at the market entry of the first biosimilar would have a more substantial effect on the total savings (as shown in scenario 3), but this variant of the price link policy is less frequently used. A design of the price link policy with a price reduction of 30% for the first biosimilar in comparison with the reference medicine price and a 15% reduction in the price of reference medicine itself at the first biosimilar’s market entry seems plausible, as this approach was identified in the legislation of some of the studied countries . HoweverAs far as tendering is concerned, the policy is employed rather rarely in the outpatient setting, while it is prevalent in the inpatient setting, documented for every country in the sample. This policy, generally known for its savings potential , can thuA number of countries have included biosimilars in their reference price system, and the results in scenarios 4 and 5 confirmed the savings potential of this measure. It should be noted that a reference price system requires sound competition among a sufficient number of manufacturers to realize its cost-containment potential. In Germany, in 2018, only three active substances  had been included in the reference price system (baseline scenario). A higher number of biosimilar suppliers on the market for a given biologic was shown to lead to lower prices of all the medicines of a specific substance (reference medicine and biosimilars) . ConsequDemand-side measures mainly aim to increase the market penetration of biosimilars. This can also bolster the attractiveness of the biosimilar market and lead to an increase in the number of suppliers and the effects of competition, thus enabling lower prices and reduced expenditure. All the countries leave the final decision on whether to prescribe a biosimilar to physicians. The majority of countries allow, or even recommend, switching patients from reference medicines to biosimilars, usually tied to certain preconditions like shared decision-making with patients and close monitoring. A few years ago even countries that endorsed biosimilar prescribing for naïve patients did not recommend switching for patients already on biologicals, but this has changed. This development reflects scientific insights driven by the so-called switch studies, which investigated the consequences of switching a patient’s medication to a (different) biosimilar. They found no negative impact of switching on safety and effectiveness, but highlighted the need for information and monitoring e.g. . The latIn contrast to generics, substitution for biosimilars at pharmacy level is not yet commonly applied; an exception among the countries in this study is Germany, where biosimilar substitution is planned to be implemented beginning of 2022. The contribution of the measure to cost-containment will have to be evaluated in due time. Any measure that influences dispensing at pharmacy level needs to be considered in conjunction with the remuneration for community pharmacy. Any price-oriented remuneration (i.e. pharmacists are remunerated for filling prescriptions based on the price of a medicine), even if designed as a regressive margin scheme, will incentivize the dispensing of higher-priced medicines . AlternaFor the calculation of potential savings from the implementation of different policies for biosimilars, this work adopted the German health system perspective. The results of scenarios 1 and 5, which were based on the lowest prices among comparator countries, indicate for biologicals what previous research  has suggEach scenario that was explored for the example of Germany has shown the potential to reduce public expenditure. It can be assumed that a combination of policies to encourage the use of biosimilar medicines would have an even higher impact. The European overview of national policies presented in “Overview of Pricing and Procurement Mechanisms and Demand-Side Measures to Endorse the Use of Biosimilars in European Countries” Section of this manuscript pointed to such bundles of measures, even though policies for biosimilars have only been implemented rather recently in some countries. Some policies are complementary, whereas other measures are applied by different actors in sequence. For instance, a price is first statutorily set by the pricing authority , and in the next stage a public procurer  tenders for the biosimilar and obtains a possibly lower procurement price, or will conclude a contractual arrangement such as a managed-entry agreement.It can be expected that the combination of supply-side and demand-side measures can amplify the effect both on the increased use of biosimilars and on savings. In particular, when in the outpatient sector tendering is combined with prescribing by INN, substitution by pharmacists and/or a reference price system, this may likely boost competition and decrease prices and, at the same time, enhance the uptake of the “winning” or “preferred” medicine, as empirical evidence has demonstrated for generics . While sAll the scenarios calculated in this manuscript led to savings for the publicly funded health system in Germany, but the scenarios based on the assumption of full implementation of a reference price system for biologicals also have an impact on private expenditure: in a reference price system (in Germany as well as in other countries), patients have to pay the difference out of pocket if they opt for medicines priced above the determined reference benchmark amount. However, the impact on patients’ expenses should be limited in extent: data only about 7.6% of all prescriptions in Germany in 2019 concerned medicines priced above the reference price .This study did not aim to provide a budget impact assessment of policy measures. Rather, by highlighting the savings potential of policies to encourage the uptake of biosimilar medicines, it adds to several budget impact assessments that have already been conducted for one or more of the biological substances investigated here  in European countries. All those studies identified important savings potentials in the case of a change from the originator reference medicine to biosimilars . While bIn conclusion, this article uses the international comparison as an instrument for generating evidence-based ideas for the development, implementation, or adjustment of policy measures. Specifically, it looked at a number of supply-side and demand-side measures that influence the prices and use of biosimilars, and thus their impact on expenditure, in sixteen European countries. While differences are observed among countries for individual measures, there are discernible tendencies . The potential for savings of some of these measures was clearly demonstrated. However, there is room for further research on the impact of other policy options (e.g. tendering or biosimilar substitution) on public expenditure not explored in this manuscript. At the same time, it is of key importance to recognize that the relative recency of biosimilars on the pharmaceutical market means that related measures have not had sufficient running time to be evaluated yet. It is therefore vital to adhere to best practice, and monitor and evaluate existing and newly implemented policies, not only regarding their effect on reducing public expenditure but more holistically, and especially in regard to patient welfare.


The kidneys are homeostatic organs that remove waste products from the metabolism and regulate the concentration of mineral, ions and the volume of body fluids. In the presence of kidney disease (KD) this function is compromised, leading to accumulation of water, minerals and waste products in the body. A close nutritional follow-up which comprises periodical nutritional assessment and supervised dietary modification is key for the management of KD , 2, playMacedo et al. showed that older adults on hemodialysis can concomitantly have malnutrition and sarcopenia, and that both conditions can be independently present in this patient group even if overweight is present. In addition, the authors also demonstrated that malnutrition and sarcopenia together have a worse quality of life and survival.This recent Research Topic on “Nutritional aspects of kidney disease” represents a collection of 11 articles, including 8 original research articles, ranging from pathophysiological-related mechanisms to body composition assessment, dietary patterns, and clinical counseling in the field of chronic kidney disease (CKD) and acute kidney injury (AKI). A common theme across the Research Topic is the assessment of nutritional status and body composition of patients with KD. This is an important topic for investigation since protein energy wasting (PEW) and sarcopenia are common in patients with KD, and are associated with adverse clinical outcomes , 5. In tGaribotto et al. thoroughly discuss this hypothesis in a very interesting and in-depth review, bringing awareness to a problem that is far from being solved.Many are the factors involved in the worsening of nutritional status of patients with CKD, including unsupervised dietary modifications, which in conjunction with the loss of appetite often observed in this patient group, may lead to spontaneous reduction in energy and nutrient intake . MoreoveSabatino et al. presented the results of an observational study that investigated the role of ultrasound (US) in the monitoring of quadriceps muscle mass of patients with AKI. They observed an important reduction in quadriceps muscle mass in the first 5 days in the ICU stay, which is expected given the strong catabolic stimuli present in this clinical setting. Overall, this paper provides evidence that US is emerging as a sensitive alternative for the body composition assessment of patients with KD. Aligned with this idea, Reis et al. investigated the role of electrical bioimpedance (BIA) in patients on peritoneal dialysis, showing how single frequency BIA seems to be more accurate than multi-frequency BIA in this clinical setting. Finally, Bellafronte et al. showed that predictive equations applied to estimate skeletal muscle mass from BIA parameters can be useful for the identification of patients with low muscle mass. In addition, Sabatino et al. discuss in a narrative review the usefulness of different bedside tools currently studied and/ or applied in the clinical practice for patients on hemodialysis. An emphasis is given to simplified creatinine index [SCI], bioimpedance spectroscopy (BIS) and muscle US, all suitable for clinical practice use. From these, US is the only method that measures muscle in different dimensions, while BIS and SCI are dependent on either theoretical assumptions or on the use of population specific regression equations, which may lead to errors when fluid alteration (over or dehydration) is present, a condition often observed in patients with KD.Unique aspects of KD, such as fluid overload and consequent body weight fluctuations, hinder a reliable assessment of nutritional status, and consequently, the management of these conditions. This topic gathers much interest and most papers from this special collection discuss or investigate different tools to assess body composition in patients with KD. Mota Silva et al. demonstrated how low lean mass as assessed by phase angle from BIA, but not inflammation and overhydration, has a moderate but statistically significant correlation with worse physical function in patients on peritoneal dialysis.A decline in physical function is also of much concern in this clinical setting, being related with increased mortality, falls, fractures, disability and low quality of life . AlthougQin et al. show how pro-inflammatory dietary patterns, as assessed by the dietary inflammatory index (DII), positively correlated with parathyroid hormone (PTH) and increased the risk of hyperparathyroidism in patients with early stages of CKD. Although it is a challenge to improve diet quality; tabus, pre-conceptions and non-evidence based dietary counseling regarding the role of fruits and vegetables in the development of hyperkalemia must be resolved, and dietitians should be called into action. That is the theme of a very interesting article published in the current Research Topic. Chan et al. evaluates the impact of individualized nutritional counseling in improving diet quality in patients with CKD, showing encouraging results.Another important challenge in the current nutritional management of patients with end stage kidney disease (ESKD) on hemodialysis is the achievement of a good dietary quality pattern . The feaWang et al. describe the risk factors for renal impairment in adult patients with short bowel syndrome; and Graidis et al. discuss the role of vitamin D in the development and prognosis of AKI as well as a therapeutic adjuvant.Finally, complementing this special collection, To summarize, we understand that this volume brings a conjunction of papers that makes up a translational point of view for the medical nutritional therapy of kidney diseases—all aligned with the unanswered questions pointed as topics requiring investigation by the KDOQI 2020 Clinical Practice Guideline for Nutrition in Chronic Kidney Disease . We are All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.