The ethics of using innovative therapies in the care of children

Abstract

An innovative therapy is a newly introduced or modified therapy with unproven effect or side effect, and is undertaken in the best interest of the patient. The ethical use of innovative therapies has been controversial. In paediatrics, the conflict between withholding potential rescue therapy and protecting a vulnerable population’s rights and welfare must be considered. Therefore, it is necessary to ensure that this innovation is conducted within an ethical framework that recognizes that the therapy is not standard. This should integrate the patient’s autonomy, the role of the institution, professional consensus and innovation evaluation. Innovative therapy represents a justifiable departure from inferior conventional therapy in the absence of an accepted standard therapy. Innovation shares with research its experimental nature, but differs from research in its goal and context that exempts innovative therapy from direct governance by research ethics board. Innovative therapy is part of the continuum of hypothesis generation in the advancement of medical knowledge, and its evaluation is a transforming point for clinical research.

With greater access to life-sustaining technologies and treatments in Canada, patients with complex conditions are surviving previously lethal diseases. These conditions often lead clinicians to junctures at which nonstandard or innovative therapies are considered. Although innovation has been a part of critical care since its inception, there may be increasing concerns regarding its safety and efficacy in the era of evidence-based medicine and ethical research. Thus, the ethical use of innovative therapies has been controversial. In paediatrics, for instance, the controversy lies in the conflict between withholding potential rescue therapy and protection of a vulnerable population’s rights and welfare. For parents, the controversy lies in consenting to unproven therapy that may carry unforeseen side effects. Furthermore, if parents decide not to consent, what other options are available to their child who has a lethal disease? Last, but not least, the controversy may arise at the institutional level regarding when and how to integrate innovative therapy in their practice. The present article reviews ethics related to the use of innovative therapies, with the aim of helping the practitioner understand the ethical issues that must be considered when they are used in the care of children.

DEFINITION OF INNOVATIVE THERAPY

Innovative therapy is a newly introduced or modified therapy with unproven effect or side effect undertaken in the best interest of the patient. Thus, an innovative therapy could be situated at any point of the continuum from genuine innovation with no precedent, such as using a new procedure or drug (ie, introducing new vaccine), to relative innovation representing a small variation from standard therapy, such as extension of therapy beyond the standard duration; or using a conventional treatment in a different context (ie, using exogenous surfactant in severe bronchiolitis). The word ‘therapy’ here is synonymous for a drug, a device or a procedure.

DISTINGUISHING INNOVATION FROM RESEARCH

For many clinicians and ethicists, research and innovation reflect essentially the same concept – that of experimentation (1,2). If this point of view is considered, the same standards of informed consent and peer review through research ethics boards (REB) need to be applied to innovative therapies that we currently apply to clinical research, and that are enshrined in the Helsinki declaration:

The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. This protocol should be submitted…to a specially appointed ethical review committee… – Paragraph 13, Helsinki Declaration (3).

Interestingly, clinicians and ethicists who argue for different standards for innovative therapies can also find justification for this point of view in the Helsinki Declaration:

In the treatment of a patient, where proven…therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new…therapeutic measures, if in the physician’s judgment it offers hope of saving life, re-establishing health or alleviating suffering – Paragraph 32, Helsinki Declaration (3).

One could find similar emphasis in The Belmont Report:

When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is experimental in the sense of new, untested, or different does not automatically place it in the category of research... (4).

The context of proposed therapies can help in distinguishing an innovative therapy from clinical research. In clinical research, the primary focus is to advance knowledge for future patients (4). On the other hand, the decision to consider an innovative therapy usually has to do with a specific patient’s care and outcome, and it may involve components of necessity and urgency (5). Clinical research follows structured standardized protocols, while innovative therapy is often neither documented nor standardized. Instead, innovative therapy is usually highly individualized and involves a dynamic context. With these significant differences between clinical research and innovation, it is difficult to hold innovative therapies to the same standards as clinical research (1). However, due to the lack of constructed safety standards in applying innovative therapy compared with clinical research, the assumption of unfavourable benefit/risk ratio could be overlooked (5,6). Therefore, it is still necessary to ensure that this innovation is conducted within an ethical framework that recognizes that the therapy is not standard (Figure 1). This should integrate patient’s autonomy, professional consensus, the role of the institution and the innovation’s evaluation (7).

Figure 1.

Interaction among innovative therapy, clinical research, patient’s autonomy, professional consensus and the role of institutional standardization to form an ethical framework

INNOVATIVE THERAPY ETHICAL FRAMEWORK

Patient’s autonomy:

In paediatrics, patient’s autonomy refers to the rights of the child’s parents or guardian to accept or refuse treatment. Thus, paediatricians should help parents make decisions concerning innovative therapy that are in the best interest of the patient. This should be through facilitating and enhancing parent’s capacity for decision-making in accordance to the family’s perspectives, culture and values (8). Information concerning innovative therapy should be communicated in a language that the parents can understand easily, and questions should be answered sufficiently. Focusing first on general goals (ie, curative versus palliative, and long-term treatment versus bridging to another therapy), then on technical options (ie, machinery support versus organ transplantation) may be a useful strategy (9).

Professional consensus:

If evidence regarding a novel therapy is absent or scanty, expert opinion could be considered as an acceptable alternative. This expert opinion could be coordinated at the institutional, national or professional organization levels.

Role of the institution:

The institution where a novel therapy is undertaken is responsible and accountable for quality assurance and risk management regarding such therapy. Also, it is the role of the institution to ensure appropriate resource allocation and distributive justice because innovation may be very expensive and utilizes significant human resources. Thus, each institution should standardize the process of introducing innovative therapy in their practice. This process should consider the structure of the institution (ie, how quality assurance is being executed and evaluated), the type of innovation (ie, surgical versus medical) and the timing (ie, elective versus emergent). For instance, if over a long weekend, a paediatrician has a dying child with fulminant myocarditis who failed maximum medical support and he wants to use a novel therapy such as a high-dose steroid in view of unfeasible cardiac mechanical support, then a fast-tracked institutional assessment through the chief physician and/or professional services, with best available literature review and expert opinion (ie, on-call intensivist and cardiologist at the same institution or at a referral centre), may be considered essential.

Innovation’s evaluation:

The evaluation of innovative therapy is an important part of any ethical framework for considering the use of innovative therapies and could be considered a transforming point from innovation to clinical research.

Radically new procedures of this description should, however, be made the object of formal research at an early stage to determine whether they are safe and effective. Thus, it is the responsibility of medical practice committees, for example, to insist that a major innovation be incorporated into a formal research project (4).

However, it is critical to define the appropriate time, number of patients and method of evaluation because innovative therapy could be confounded by many extraneous variables such as outcome latency, learning curve, and type and nature of innovation (10). Therefore, understanding the limitations of the evaluation of innovative therapies should be part of the process.

INFORMED CONSENT FOR INNOVATIVE THERAPY

Informed consent is the cornerstone for ethical innovation. However, in the situation of innovative therapy, the conundrum with respect to consent would be how much of the informed consent can actually be considered ‘informed’, in view that innovation often means that there is absent or scanty information regarding such therapy. Also, given the context of innovative therapy, which includes no accepted standard alternatives, the parents may feel that they are left with no other choice. Furthermore, if emotional factors are added, such as terminal cases, it becomes even more difficult to judge this consent as informed consent. On the other hand, information regarding the innovation could be biased if presented by the person who owns the innovation. Therefore, informed consent should address these important issues clearly to preserve the autonomy of the decision makers.

SUMMARY

• Innovative therapy is a newly introduced or modified therapy with unproven effect or side effect undertaken in the best interest of the patient.

• Innovative therapy shares with research its experimental nature, but differs from research in its goal and context in that it is exempt from REB direct governance.

• Within a structured ethical framework, innovative therapy represents justifiable departure from inferior conventional therapy in the absence of an accepted standard therapy.

• Innovative therapy is part of the continuum of hypothesis generation in the advancement of medical knowledge and its evaluation is a transforming point to clinical research.

RECOMMENDATIONS

• Paediatricians should understand the ethical issues involved in using innovative therapies.

• Paediatricians should help parents make decisions concerning innovative therapy that is in the best interest of the patient, by facilitating and enhancing parents’ capacity for decision making in accordance to the family’s perspectives, culture and values.

• Institutions where innovative therapy is practiced should standardize the process of evaluation and approval that best fits with their structure and available expertise. This includes consent format, indications, limitations and reporting.

• Informed consent must state the nature of the innovation and must provide the best available information, including the consensus of expertise at the institution and/or national level concerning the innovative therapy use, and whether alternative therapies may be available. Also, informed consent should include optional data collection for future institutional review.

• The physician who does not own the innovation but is equally informed about it should obtain consent from the patient. If such a physician is not available, the physician who owns the innovation should obtain consent from the patient with disclosure of his bias and potential conflict of interest.

• Review, analysis and reporting of innovative therapy must be carried out at the earliest possible time when data are judged to be meaningful. This includes adequate number (ie, three patients or more) and adequate adjustment for the learning curve and outcome latency (11). The conclusion should be anonymously available for current or future patients treated with the innovative therapy and should be reported to the local REB.