Eminence or evidence? The ethics of using untested treatments

Loane Skene does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations

beyond their academic appointment.

The Conversation UK receives funding from these organisations

TRANSPARENCY AND MEDICINE – A series examining issues from ethics to the evidence in evidence-based medicine, the influence of medical journals to the role of Big Pharma in our present and

future health.

Today, Loane Skene considers circumstances in which it may be appropriate for a relatively untested treatment to be offered to patients.

There are times when a new therapy seems superior to existing treatments. But is it ethical to offer people a new treatment that some clinicians believe from treating their patients is

effective (“eminence-based” treatment), but which hasn’t been subject to properly designed clinical trials (“evidence-based” treatment)?

One example of such a treatment is charged particle therapy (CPT), which uses protons or light ions, such as carbon, to treat cancerous tumours instead of conventional X-ray therapy. CPT is

about 2.4 times more expensive and it hasn’t been subject to randomized clinical trials.

Generally, we expect such trials to take place before an alternative treatment is used to treat patients. But some experts in the field believe there’s sufficient evidence from physics and

reported cases to show that CPT has advantages over conventional X-ray treatment.

CPT can be confined more closely to the region to be treated, for instance, whereas conventional techniques are much broader and bring with them the risk of affecting healthy tissue as well

as the tumour.

Some doctors have been offering the treatment to their patients and more than 70,000 people have now been treated worldwide with CPT, mainly for eye tumours.

These issues were considered at a recent, cross-disciplinary, international workshop hosted by the Oxford Martin School.

The workshop was described as a world first because of its focus on the ethical process for introducing a specific alternative treatment in the face of scientific uncertainty.

A resulting report is yet to be published but the following are some of the principles for proceeding ethically with new treatments. They are based on my impression of discussions at the

workshop and not the report itself:

It’s ethical to enrol patients in a randomized clinical trial if there’s some uncertainty or reasonable doubt about whether one treatment or another is better. This is the principle of

equipoise that justifies medical research.

In deciding whether there’s reasonable doubt about the efficacy of a treatment, a comprehensive range of stakeholders from various disciplines should be consulted, including those with

different views.

A thorough review of current practice, open to the public, should be undertaken, including a review of the available evidence and the quality of that evidence.

Even if this process establishes a “reasoned” disagreement in the community of scientific experts, or finds a lack of evidence about the better alternative (making a randomized clinical

trial ethically justifiable) that doesn’t mean it’s always ethically necessary or desirable to conduct such a trial.

There may be sufficient reason to offer the alternative treatment if there’s evidence from data sharing – reports from researchers and clinicians worldwide on the use of an alternative

therapy for their patients.

To be statistically sound, all patients treated with this therapy would need to be recorded, perhaps overseen by an independent organization, including any negative results and side-effects,

using standardized protocols and data collection.

Even if clinical trials are ethically justified, individual clinicians are not ethically required to enrol their patients in a trial. Exercising clinical judgment, they may disagree with

other experts, have limited facilities to use the new therapy, or believe their patients aren’t suitable for the new treatment.

Patient or community representatives, who can understand the risks for patients, should be consulted about whether particular research and clinical treatment should proceed.

Research ethics committees should be responsible for protecting participants from undue risks. They would do this by ensuring risks are minimized by sound study design and are reasonable in

view of the knowledge to be gained.

Patients are entitled to decide for themselves whether to participate in a clinical trial, weighing up quality of life and survival, and taking risks to help the community, guided by their

own clinician on the accepted principles of informed consent.

Some experts strongly believe CPT has great potential and can ethically be used before clinical trials have been conducted.

Other clinicians say there’s limited evidence about the efficacy and safety of CPT and studies to date have been mainly retrospective with small numbers.

tissues may be affected differently by different types of radiation;

it’s difficult to ensure the particles in CPT are delivered to the precise target; and,

if there’s an error, consequences may be serious for the patient, such as paralysis and double incontinence when treating a tumour near the spine.

This disagreement among the community of experts justifies clinical trials being undertaken. Research ethics committees would then assess the potential risks for patients before approving

the trials.

Clinicians would decide whether to enrol particular patients. And patients would decide whether to participate if offered the opportunity.

But CPT could ethically continue to be offered to patients without clinical trials if clinicians are willing to do this, subject to ethical oversight and patient consent. In Australia, the

approval of the Therapeutic Goods Administration would presumably also be required.

There is some evidence that CPT is effective and more information will be collected as more treatments are offered. The number of machines and centres offering CPT is increasing

exponentially, doubling every eight years, so it is increasingly being funded and used.

If there is a reasoned disagreement between experts about new treatment, a clinical trial is justified but treatment can ethically be given in the interim if there is other evidence of its

efficacy from case reports and data sharing.

This is the fourth part of Transparency and Medicine. You can read other instalments by clicking the links below:

Part One: Power and duty: is the social contract in medicine still relevant?

Part Two: Big debts in small packages – the dangers of pens and post-it notes

Part Three: Show and tell: conflicts of interest undeclared for clinical guidelines

Part Five: Don’t show me the money: the dangers of non-financial conflicts

Part Six: Ghosts in the machine: better definition of author may stem bias

Part Seven: Clearing the air: why more retractions are good for science

Part Eight: Pharma’s influence over published clinical evidence

Part Nine: Insight into how pharma manipulates research evidence: a case study

Part Ten: Why data from published trials should be made public

Part Eleven: Open disclosure: why doctors should be honest about errors

Part Twelve: Reaching full and open disclosure for universities, medical schools and doctors

Part Thirteen: Ethics of accepting suppliers’ gifts in the business v medical world

Part Fourteen: Conflicts of interest in guideline development: the NHMRC responds

Part Fifteen: Consumer input in Medicines Australia’s code of conduct review