OA: Does clinical trial participation improve outcomes in patients with ovarian cancer? | ESMO Open

 Definition of tertiary care

:  highly specialized medical care usually over an extended period of time that involves advanced and complex procedures and treatments performed by medical specialists in state-of-the-art facilities                 ```````````````````````````````````````````
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Results

Sixty patients with ovarian carcinoma were evaluated; 30 were treated on trial and were matched with 30 patients who had received the same chemotherapy (carboplatin and paclitaxel or carboplatin alone) off trial. Patient baseline characteristics are shown in table 1.

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Table 1

Characteristics of patients with ovarian cancer

Key questions

What is already known about this subject?

• Trial effect describes the phenomenon whereby patients receiving standard of care (SOC) as part of a clinical trial have superior survival compared to those on SOC off trial.
• Systematic reviews to date do not support trial effect but were performed before many SOC regimens were adopted.

What does this study add?

• It is the first cohort study performed in the era of modern therapy for patients with ovarian carcinoma.
• It does not support the phenomenon of trial effect in a tertiary centre.
• It highlights the need for more research into the differences (if any) of core components of care that patients receiving SOC treatment on clinical trials receive compared to those off trial.

How might this impact on clinical practice?

• Once defined, the core components or principles of care could be applied in all settings to promote the highest SOC for all patients regardless of centre of care.
• At the current time, participation in a trial even if a SOC arm is offered is still considered beneficial.

Introduction

Participation in clinical trials is often promoted as the best treatment option for patients with cancer. While some clinical trials have the potential to offer more effective treatments than standard of care (SOC)—BRAF inhibitors and checkpoint inhibitor antibodies in metastatic melanoma being prominent examples1–4—most randomised clinical trials (RCTs) do not produce positive outcomes. In a systematic review of 253 RCTs, two-thirds of clinical trials failed to meet their primary endpoints.5 Furthermore, in large phase III trials where SOC is used as a control arm, up to half of enrolled patients will not experience any additional therapeutic benefit. It is important to ask, therefore, whether receiving SOC on trial results in improved outcomes for these patients.

‘Trial effect’ describes the phenomenon of improved health outcomes in patients treated with SOC on trial compared to those receiving SOC outside of a clinical trial setting. A number of variables have been posited as contributors to this so-called effect but it is unclear whether these are attributable to the treatment setting (which tends to be tertiary centres with greater expertise and resources than hospitals that are not research-intensive) or explainable by other psychologically-mediated factors such as patients' or clinicians' increased expectations of success. The trial effect may, moreover, simply be an illusion created by selection bias, as stringent eligibility criteria that exclude less fit patients may mean trial participants are already likely to fare better than their counterparts receiving SOC outside of the research context.

If health outcomes are superior in patients receiving SOC on trial, then the push to enrol patients into trials may be justified even if some patients will be disappointed when they are deemed ineligible to participate. From an ethical perspective, a better understanding of trial effect is essential because it challenges a concern of those involved in the research ethics review process. Since Appelbaum et al6 first introduced the concept of the therapeutic misconception in 1982, clinician-researchers have been urged to avoid descriptions of their trials that may conflate research and therapeutic aims; however, despite decades of work on the language of informed consent, the distinction is quickly blurred when participants are desperate for cures and researchers are eager to confer benefits on them.

There is a paucity of evidence in the literature on ‘trial effect’......

If outcomes are better in tertiary centres of excellence with active research environments, it is necessary to ask, what are the essential components of these centres that need to be introduced to peripheral sites or is this indeed possible or cost effective? Patients may like the convenience of treatment closer to home but they should be made aware that they may not receive the best care if local facilities are limited in specialist expertise.

Our study supports patient enrolment in clinical trials. The benefits of trial participation extend beyond their effects on individual trial entrants. There is a potential for providing best practice to all patients with cancer.