Many new and expensive treatments are coming onto the market, raising an ethical dilemma of how to prioritise the financial resources available in the health care system. Biological drugs are an especially expensive form of treatment in a field where many new drugs are currently being developed.Reference Ecker, Jones and Levine1 Decisions about how scarce medical resources ought to be prioritized involve individual and political values. Resources in a health care system are always limited and implementing an expensive treatment in one area leads to fewer resources available in other areas. It is important to investigate this ethical problem since a better understanding of its basis may nuance the discussion and illuminate how different parties weigh various aspects of the issue. The American ethicists Tom Beauchamp and James Childress, warn that: “Countries lacking a comprehensive and coherent system of health care financing and delivery are destined to continue on the trail of higher costs and larger numbers of unprotected citizens. They need to improve both utility (efficiency) and justice (fairness and equality).”Reference Beauchamp and Childress2

In 2018, the Danish Council on Ethics published a report on the just distribution of resources in the Danish health care system.3 The Danish Council on Ethics advises the Danish parliament on request and initiates public discussions on ethical subjects. The report clearly identified increases in the cost of medical treatments, access to treatments, and the allocation of resources between different disease indications as ethical problems of justice, distributive justice, and beneficence. Furthermore, the report states that these ethical issues are notoriously complicated and that explicit decision-making instruments are needed in health policy to determine how to set priorities. The report concludes that the decision-making instruments should be based on well-founded ethical principles, here, at least in part, citing Beauchamp and Childress.4

Ethics committees in other countries also worked on the subject of prioritising treatments and found no clear answer on how to distribute resources. The Norwegian National Research Ethics Committees published an anthology about research and money, which discusses subjects such as the relationship between the pharmaceutical industry and medical professionals and the price of a human life. No recommendations were given, but the anthology was intended to start a debate about money and health.Reference Fossheim and Ingierd5 The Austrian Bioethics Commission has discussed the balance between morality and economics, and it recommends transparent solutions and that limited resources are used as responsibly as possible.6 The German Ethics Council stated that it is impossible to reach consensus among the parties involved and recommends an open debate involving medical, economic, ethical, and legal expertise to avoid decisions exclusively based on economics, and that rationing decisions should never be made by the individual nurse or physician.7

From a utilitarian standpoint, improving utility should be done by maximising health for the resources available. At an American hospital, it was shown that expenses for costly treatments could be markedly reduced by implementing a review process of their effect.Reference Durvasula, Kelly, Schleyer, Anawalt, Somani and Dellit8 After all, what is the point in using expensive treatments without evidence for effect? But a costly treatment might have a small effect. Who should then have the authority to decide whether the effect is worth the cost? Giovanni Maio argues that the treating physician should not be a gatekeeper of resources.Reference Maio9 Instead, politicians should set overall guidelines, while the physicians should make the medical decisions, deciding whether a treatment is futile or not. Otherwise, the relationship between the physician and the patient will be shaken.10 Such economic decisions can be made using Quality-Adjusted Life Years (QALYs). However, this method has been widely criticised. One critique is that saving the life of a person in a wheel chair yields fewer QALYs than saving the life of a person not in a wheelchair, which, as it was argued, is not ethically justifiable.Reference Nord11 Beauchamp and Childress also criticise the use of QALYs. For instance, they do not support that health maximization is the only factor evaluated, as it is in a QALY analysis, because other values, such as the way the care is provided, are also important. They also argue that the QALY calculation implies that it is better to save one person with a life expectancy of 40 QALYS than saving two people with 19 QALYs each, which they do not necessarily support.12 A strictly utilitarian way of distributing resources focused on health care maximisation by calculating QALY-gains could therefore give rise to ethical concerns.

Beauchamp and Childress present a framework for ethically justified decision-making in their book Principles of Biomedical Ethics.Reference Beauchamp and Childress13 This book was first published in 1979 and has been revised over the years with the latest 8th edition published in 2019. In this study, the 7th edition published in 2013 is used, as the edition was the newest available version at the time of the interviews. Beauchamp and Childress present four principles central for biomedical ethics. These principles are beneficence, nonmaleficence, respect for autonomy, and justice. According to Beauchamp and Childress, one should consider what is at stake for each of the principles, and then weigh and specify the principles in dialogue with the parties involved.14 This approach has been widely used in the field of biomedical ethics.

In the field of healthcare, the four principles of biomedical ethics can be used to identify the issues at stake in an ethical dilemma. An example is given in a paper on the use of biological therapies for dermatological diseases in the US.Reference Santoro, Rothe and Strober15 Based on the principles of beneficence and nonmaleficence, the authors argue that the most optimal treatment option for the patient should be found based on effect of the treatments available and the physician’s experience from previous patients. According to the principle of respect for autonomy, the decision should be made jointly by the physician and the patient based on the patient being informed about risks and side effects. With regard to the principle of justice, these authors concluded that the patient should receive the biological treatment if it is considered medically necessary even though the price is high. If the patient’s insurance cannot cover the cost, a biosimilar option could be considered.16 In consequence, the result of the justice discussion varies depending on the organisation of the health care system and the fact that the patient might have to pay for some of the drugs herself. These costs might be high and, therefore, it was suggested that economic barriers for effective cancer treatments in the US should be removed.Reference Fleck and Danis17 Some patients may be forced to end an effective treatment because of costs, and drug prices can suddenly rise without a clear reason. Furthermore, the US federal health insurance program Medicare has been criticised for not having the possibility of negotiating drug prices.18

As just outlined above, this ethical dilemma is different, depending on the organisation of the health care system. Beauchamp and Childress advocate a two-tiered health care system with a right to a decent minimum of health care. This model is built on egalitarian and utilitarian theories of justice.19 This way of organising a health care system is in line with the Scandinavian model of health care, including the Danish system, which is also the context of the study presented below.

Mette Ebbesen and Birthe D. Pedersen showed that the ethical principles by Beauchamp and Childress are applicable to the daily work of Danish molecular biologists and oncologists.Reference Ebbesen and Pedersen20 They investigated how molecular biologists and physicians in Denmark perceived the four principles and found that all four principles were reflected in their daily work, although these two groups of respondents had different perceptions of nonmaleficence and respect for autonomy.21

In the present study, the four ethical principles of Beauchamp and Childress were used as an open framework to structure the data analysis. This study investigated whether these principles are at stake in the process of decision-making involved in prioritising access to expensive biological treatments in Denmark. The chronic disease multiple sclerosis was used as an example. The following three themes were investigated:

1. Whether the four principles of biomedical ethics are at stake in the discussion about prioritising resources for biological treatments.

2. What specific content of each principle is at stake, and whether some related issues not covered by the principle or the interviewer are at stake.

3. How the principles are weighted and specified in this ethical dilemma.

Background

The Danish Health Care System

The Danish health care system provides mostly free medical treatment to all citizens and is financed by taxpayers. Around 30% of the population have private insurance, providing them access to faster treatment and around 40% have insurance that gives subsidies for prescription medicine, dentist bills, spectacles, etc.Reference Houman22

The Danish Medicines Council evaluates drugs and establishes guidelines for the use of drugs for the various therapeutic fields. The price of each drug and the evidence for its effect are analysed by the Council in the process of recommending drugs. This is done to ensure the quality of treatments, homogenous treatments across the regions of Denmark, and a reasonable correlation between the price and the effect of drugs.23

Biological Treatments

Biological therapies are often offered to patients in the Danish health care system as part of the treatment of common diseases such as cancer, arthritis, and MS. These biological therapies are more expensive than other kinds of treatments offered24 with typical costs of DKK 45,000–250,000 a year per patient [USD 7,200-40,000 (exchange rate, September 2020)].25 The prices were obtained February 2020 and the price movements per unit, since the conduction of the interviews November 2017 – January 2018, are inserted in the note number 25. At least in part, the costs of the drugs relate to the complex manufacture of proteins expressed in living cells.Reference Gamez-Belmonte, Hernandez-Chirlaque, Arredondo-Amador, Aranda, Gonzalez, Martinez-Augustin and Sanchez de Medina26 These drugs are typically large molecules, e.g. the so-called antibodies. Antibodies are produced as part of normal physiology in the body during the immune response to challenges with “non-self ” molecules, notably proteins, as would happen when infectious agents intrude in the body. Typically, antibodies bind very specifically to their targets, in this way avoiding reactivity with “self ” molecules. At the end of the 19th century, it was discovered that antibodies raised against specific targets can work efficiently as a treatment.Reference Hey27 It is not possible to make generic copies of biological treatments due to the natural complexity of the molecules, which involves small variations in the molecules, mainly in attached carbohydrate structures or chemical modifications of the amino acid residues through oxidation or deamination.28 These variations arise in the production and storage of the drugs. Therefore, copies of biological drugs are referred to as biosimilars, since these are not identical, but similar to the original product. Consequently, biosimilars must undergo stricter pharmaceutical and clinical testing than simpler generic drugs.29 This is an expense for the manufacturer, which reduces competition in the field. Less competition and an expensive manufacturing process are two parameters that contribute to the high price of biologicals and their biosimilars, although price setting is a complex subject and prices might not correspond to development costs. An indication that prices do not necessarily correspond to development costs, is found from how much money the hospitals can save by switching all patients from the original drug to a biosimilar drug, when the original drug no longer is the only drug on the marked.30

Table 1 shows how an effective but expensive form of treatment raises ethical questions about choosing a treatment and prioritising resources.

Table 1Example of a disease field with expensive treatment options.

Many different players and interests are at stake for the use of biological treatments. Researchers perform the basic research to find new biological treatments. These findings are further developed by the pharmaceutical industry to make it into medicine. Physicians use the medicine to treat the patients in the Danish health care system, which is led by politicians. Politicians have chosen to form the Danish Medicines Council to make treatment guidelines. All these different players have different opinions on the use of biological treatments, which make their perspectives relevant to investigate.

Method

Ethical Theory

This study used the principles of Beauchamp and Childress as an open framework for the overall design of the study, the interview guide, and structuring the data analysis. According to Beauchamp and Childress, in an ethical dilemma, these principles must be specified and weighed against each other to make an ethically justified decision. The four principles are briefly presented in Table 2, below.

Table 2The principles of biomedical ethics by Beauchamp and Childress.

Beauchamp and Childress propose that there is a common morality for morally serious persons. Furthermore, they specify that the four ethical principles are a part of this common morality. According to Beauchamp and Childress, therefore, all morally serious persons find the principles relevant and important.33 Beauchamp writes: “The common morality is not merely a morality that differs from other moralities. It is applicable to all persons in all places, and all human conduct is rightly judged by its standards.”Reference Beauchamp34 The common morality contains basic principles, virtues, and obligations for instance the principle of respect for autonomy — and, as specified in contexts of medicine and research — the obligation of informed consent. These principles and the obligations that descend from them have prima facie standing and are part of the common morality on the same normative level as the principles of beneficence, nonmaleficence, and justice. These principles and the obligations they generate are universal and not culture sensitive. Therefore, the right of informed consent is a universal right to give “an autonomous authorization by individual patients or subjects” when an intervention is proposed.35 It is not a culturally relative principle or right.

However, specifications of these basic principles and overall obligations into more specific rules, procedures, etc. may in some contexts be culturally sensitive, especially when these norms are component parts of particular moralities that are nonuniversal such as codes of ethics for medical societies.36 While the obligation of a health professional to obtain an informed consent that authorizes an intervention may be essentially universal, by contrast, the elements of the specific process of authorization of informed consent as part of particular morality can be culture guided. The specific process of authorization also may be deeply rooted in cultural practice. For example, families may play a much larger role in the process of authorizing than health professionals even though basically a true informed consent for a competent patient or subject is a first-party consent.

By “culture,” we here refer to culture as multidimensional and including knowledge, beliefs, arts, specific rules, laws, customs, and any other capabilities and habits acquired by a human as a member of society. In addition, national, ethnic, religious, regional, and generational considerations can have some role in creating a wide range of cultures with many differences.Reference Halkoaho, Pietila, Ebbesen, Karki and Kangasniemi37

In order to achieve a valid informed consent as “an autonomous authorization by individual patients or subjects,”38 health researchers should discuss with patients and subjects any known cultural consideration that might affect the decision to authorize or refuse an intervention. This obligation of health researchers reflects the positive (active) obligation of respect for autonomy, which refers to “respectful treatment in disclosing information and actions that foster autonomous decision making.”39 In that sense, health researchers are obligated “to disclose information, to probe for, and ensure understanding and voluntariness, and to foster adequate decision making.”40 Beauchamp and Childress describe the content of the concept of authorization in medical contexts as follows: “Patients and subjects usually should understand, at a minimum, what an attentive health care professional or researcher believes a reasonable patient or subject needs to understand to authorize an intervention. Diagnoses, prognoses, the nature and purpose of the intervention, alternatives, risks and benefits, and recommendations typically are essential. Patients or subjects also need to share an understanding with professionals about the terms of authorization before proceeding. Unless agreement exists about the essential features of what is authorized, there can be no assurance that a patient or subject has made an autonomous decision and provided a valid consent.”41

The theory of Beauchamp and Childress has been criticised over the years. In the preface to the 7th edition of their book, the authors write that many critics argue that the theory has an American individualist orientation and that the principle of respect for autonomy overrides the other principles.42 Beauchamp and Childress argue that this is a misinterpretation and emphasise that no principle is overriding. Søren Holm says that the theory is based on an American common morality, which is not always transferable to other societies.Reference Holm43 However, Holm misinterprets Beauchamp and Childress’ account. Beauchamp and Childress clearly differentiate between two normative levels, the one of the common morality as universal and the other of particular moralities as nonuniversal. Beauchamp writes: “Universality is located in the common morality and nonuniversality in other parts of the moral life, called ‘particular moralities.’”44 The four principles of biomedical ethics and the obligations that descend from them are part of the common morality and are hence universal. These principles are then specified and balanced in particular moralities, and these specifications and the specific process of balancing are culture sensitive and hence, nonuniversal. Holm does not consider this differentiation between two normative levels and he does not recognise that Beauchamp and Childress consider the basic principles and basic obligations as universal and the specific process of specification and balancing as nonuniversal.

Sample and Sampling Procedure

This study was based on eight semi-structured interviews with Danish respondents who are familiar with and have experience in the field of antibody therapy, MS, or prioritising resources for expensive treatments. These respondents include important stakeholder positions, e.g. patient, physician, and politician. This allows various different perspectives on the ethical problems in decision-making and the allocation of expensive biological treatments to be explored. The description and background of the eight respondents are presented in Table 3.

Table 3First column: description of the respondent. Second column: background of the respondent.

The type of sampling used is purposive sampling,Reference Silverman45 based on the everyday work of the respondents. The respondents were specifically selected to make it possible to explore multiple aspects of the issue of expensive treatments and MS in Denmark. The respondents have been anonymised.

Interviews and Interview Guide

The eight qualitative interviews were conducted using a semi-structured interview guide. This interview format was chosen to let the respondents reflect on the questions and to clarify their considerations. Each interview lasted 40–62 minutes and was recorded and transcribed word-for-word. The interviews were conducted in the period November 2017 – January 2018.

The questions in the interview guide were divided into 6 groups as shown in Table 4.

Table 4Structure of interview guide.

Data Analysis

The data from this study were analysed using a phenomenological hermeneutical method for interpreting interview texts inspired by the philosopher Paul Ricoeur’s theory of interpretation.Reference Lindseth and Norberg46 The interviews were transcribed word-for-word in text form. To enter the hermeneutical circle, the data analysis has three stages: 1) naïve reading, 2) structural analysis, and 3) critical interpretation:

1. Naïve reading: the transcribed text was read several times with an open mind, in an attempt to understand the whole text without bias.

2. Structural analysis: the text was divided into units, which might be a sentence or part of a sentence. The meaning of these text units was condensed to cover only the most relevant points. These were further condensed by making themes and subthemes for the units. The structural analysis was compared to the naïve reading. An example of the structural analysis is shown in Table 5.

3. Critical interpretation: the themes and subthemes were compared to the research questions, previous studies, and the literature.Reference Ebbesen and Pedersen47 The bioethical principles of Beauchamp and Childress were used in this last stage of the data analysis to structure and inspire the data interpretation.

Table 5Example of structural analysis from the present study.