Introduction

Cancer is a complex disease with many different types that affects people in a plethora of ways and is a leading cause of global mortality. Because of this, there is a constant ongoing development stream of experimental new drugs and therapies with the hope of finding effective treatment options for the numerous types and symptoms of cancer. 

These experimental treatments need to undergo a series of thorough clinical trials, including testing on human patients, to ensure that they are effective and that any benefits outweigh potential risks. Developing new treatments often poses ethical concerns and progress must be balanced by respecting patient rights. 

When patients partake in experimental clinical trials, their autonomy must be respected, and they must be fully and meticulously informed about the nature of the trials before their consent can be obtained. Below we will discuss some of the ethical considerations in experimental cancer treatment, such as patient rights and potential vulnerability, access and accelerated approval of treatments, and the nature and ethics of clinical trials.

Patient rights in experimental cancer treatments: autonomy and informed consent 

A patient's right to make their own informed decisions regarding their health must be maintained. Regarding experimental cancer treatments, this means risks and their likelihood are clearly highlighted alongside potential benefits. It is important that patients understand the experimental nature of the treatment, and that they may receive a placebo. If informed consent is not enforced rigorously, it can allow room for vulnerable patients to be unfairly exploited.

However, it is not always so simple. There is a lot of inherent uncertainty regarding experimental treatment as the chances of benefits and risks and what they may entail are not understood. Can a patient be determined to have given informed consent if the outcomes are not known or understood by the informer? In the case of children, the age from which they can legally provide informed consent will vary by country. There are also practical considerations. How do those administering the trials consistently and effectively ensure all participants are adequately informed about what they are signing up for? 

It has been reported that participants in clinical cancer trials do not always fully understand the implications of the treatment they are receiving and that efforts to improve patient understanding before participation should be made.^1,2,3

Vulnerability of patients

Cancer patients are often in a vulnerable state of mind, especially in the case of a terminal diagnosis. For some, this can have a major influence on the decisions they make. Patients may accept the offer of experimental treatment without fully accounting for the risks or likelihood of efficacy. 

This poses ethical concerns as to whether patients are in a position to be exploited to further the progress of clinical trials. Everyone involved, from researchers to healthcare providers, has a moral duty to protect patients, meaning ensuring a clear understanding of the potential outcomes is the foundation of the patient's voluntary participation. 

The Belmont report is a seminal document authored in the U.S.A. by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research. It compels researchers to prioritise patient protection and respect and to approach clinical trials purely from a position of patient beneficence.⁴ This means constantly being aware of the risk-benefit ratio of their studies and how it might change and effectively communicating this to patients. 

Many experimental treatments carry risks such as adverse side effects and the eventuality that they may not have a significant therapeutic effect. Patients must understand this so as not to generate undue false hope. 

Access to experimental treatments

Who has access to experimental treatment is another area of concern. Patients typically have to meet strict criteria to be eligible. In some cases, they may have to have specific resources available to them to take part, e.g. a car to travel. This can generate or exacerbate health disparities between different groups on a global and community level. 

Subject selection should be based purely on scientific objectives, not the vulnerabilities or privileges of the patients, and the primary determining factor for the selection of study sites should be the distribution of risks and benefits.⁵

Unfortunately, the practicalities of achieving equity in access to experimental treatment are complex and challenging. Trials may take place in centres that are unreachable to many patients. Strict eligibility requirements necessitate the exclusion of patients for various reasons such as age, sex, comorbidities, or previous treatment. 

Many support expanded access or compassionate use, whereby patients are given access to experimental treatment outside of clinical trials to address these issues. However, this should only be done when there is no viable alternative.⁶

The importance of clinical trials

Clinical trials are the primary pathway through which medical treatments and therapies are tested and validated. They are crucial in providing scientific evidence that advances medical progress and develops treatments for improved patient benefit. How these trials are executed is enveloped by complex ethical issues. The potential benefits to be gained by researchers must outweigh the risks to participants, especially when treatment is experimental and unproven.

The randomised controlled trial (RCT) is considered the gold standard of clinical research, in that it produces data with the most validity regarding the efficacy and safety of new treatments. However, RCTs pose ethical concerns, especially in trials where patients are randomised into placebo treatment. With potentially terminal diseases like cancer, it is a serious ethical issue not to provide possibly effective treatment to patients purely for scientific rigour. 

This is why participation in placebo and treatment groups must be truly randomised. Some ethicists argue that this fact makes the use of placebos unethical in this circumstance, and alternative trial designs should be sought. Placebo trials must only be used when there are no other viable treatment options, other than the treatment being tested in the study, which of course its efficacy is unknown. To give a patient a placebo for the sake of a clinical trial when a viable alternative treatment is available is a major breach of medical ethics.⁷

Balancing individual and collective interests

There is a theoretical balance to be struck between protecting and prioritising the immediate needs of individual patients and the long-term goals of clinical trials to benefit the wider population. The problems associated with finding this balance can be exacerbated by compassionate use or expanded access programs in which patients seek to gain access to experimental treatments outside of a clinical trial setting.

Compassionate use programs provide patients, with grave or life-threatening diseases, with access to an experimental medical treatment before it has been approved by regulatory authorities. While these programs offer essential options for patients for whom no alternative exists, they also raise ethical issues. Critics see compassionate use as undercutting the clinical trial process, siphoning off potential participants and thereby slowing down research progress, delaying approval of new treatments for the population at large.⁸

Ethical implications of accelerated approval

It is important to consider accelerated approval in individual cases thoroughly, although its benefits are obvious in that they can provide potentially effective medicine to severe cases quickly, the ethics of accelerated approval are complex.

Often, the data supporting accelerated approval is based on surrogate endpoints, that is, a quantifiable measurement, such as tumour shrinkage, that doesn’t portray the full picture, such as improved quality of life or survival rates. This can make it easy for medical professionals and patients to be misled about the benefit-risk ratio of a treatment option, which has massive implications for the concept of informed consent.

Accelerated approval can also lead to new treatments being brought to market before their long-term safety and efficacy are truly known. This puts patients at risk and questions the responsibility of regulatory agencies and pharmaceutical companies in evaluating the efficacy and risk-benefits of treatment before approving their availability to the public.⁹

Conclusion

The ethics of experimental cancer treatment are broad and there is no one-size-fits-all approach, ethics must be considered on a case-by-case basis, dependent on the needs of the patients and the potential benefits the completion of a clinical trial can bring to the wider population. 

The principles of informed consent, patient protection beneficence, and equity in access to experimental treatment are some of the core principles in maintaining the ethics of experimental cancer treatment clinical trials. Simultaneously, the need for medical progress is essential and must be balanced with patient rights, and not prioritised at their expense.