SGO Ethics | The Treatment Dilemma: Choosing Between Standard of Care Versus Clinical Trials | Ursula Matulonis, MD & Anil K. Sood, MD
Anil Sood, MD
Dr. Sood: In a packed clinic recently, I sat with a patient who has platinum-sensitive relapsed ovarian cancer and discussed various treatment options with her. She had been on a PARP inhibitor for maintenance, but unfortunately developed recurrent disease. I knew that surgery was not an option because of the extent of disease. The standard of care answer would have been to recommend a platinum-based regimen. But, I also knew that there were clinical trials available that were testing new drugs with a PARP inhibitor, some of which were showing interesting results. After our discussion, she and her husband both looked up and said, “we trust you – what do you recommend?”
This was a very simple question, but I felt a sudden rush of questions running through my mind: What is the right thing to do and how should I reply? Will I be hurting this patient if I recommend the clinical trial? What if she goes on the trial and ends up with a complication? Since she had progression on a PARP inhibitor, is standard of care platinum-based regimen still likely to help her? For some reason the weight of these questions was bothersome enough that both Dr. Matulonis and I discussed this at length at a recent meeting and felt that this might be a good topic for discussion on this blog.
These are relatively common questions that we face. While there may not be “right” answers to these questions, they do bring up some fundamental topics to consider. As oncologists, we often face difficult decisions when it comes to offering treatment options to patients. Both standard of care and a clinical trial have their potential benefits and risks.
Ursula Matulonis, MD
Dr. Matulonis: I agree, Anil. As oncologists, we make these decisions with our patients every day, and it’s understandable that they want our opinion regarding the appropriateness of a clinical trial since we understand the biology of their cancer, what the cancer’s clinical course is predicted to be, and sometimes the possible activity of the clinical drug or drugs. But, many times, we don’t have a sense of the anti-cancer activity of the drug or drugs in a clinical trial, especially a first-in-human trial or an early phase II study. There are times when the study fits the patient, her clinical situation, and her cancer biology: a biomarker predicting a response is present and perhaps the next standard of care options may have lowered expectations clinically and/or are particularly toxic. But, in your patient’s case, standard of care has a very reasonable chance of efficacy, and the addition of a new drug could cause harm. However, participating in the study may result in a longer remission. That is the hard part for the patient who has to ultimately make the final decision.
Dr. Sood: At the core of medical ethics is the principle of patient autonomy, which asserts that patients should have the right to make informed decisions about their healthcare. That should include providing the patient with full information about the benefits, risks, uncertainties, and potential outcomes of each path. However, clinical trials often come with uncertainty, as they test unproven treatments that may not yet have demonstrated efficacy. In contrast, the standard of care is a more predictable option, backed by evidence and practice. As oncologists, we must ensure that the patient understands these nuances clearly and is fully aware of the risks of both options without feeling pressure toward one option. At a personal level, these can be very difficult decisions, and the patients and families may look to the oncologist for guidance in their decision making. It is the physician’s duty to act in the patient’s best interest. Recommending the standard of care is a relatively safe and reliable option. Recommending the standard of care is often seen as an ethical default. But, does that standard still hold in the era of maintenance therapy? In contrast, clinical trials may offer the possibility of access to cutting-edge treatments that could provide greater benefits, but the outcomes are uncertain.
Dr. Matulonis: These types of decisions are sometimes challenging to make, but I agree that our duty and job is to always act in the best interests of our patients. The NIH has a strategy on its website originally formulated for pediatric patients that can be used to guide care for our adult patients to ensure that we are educating and explaining clinical trials as best as we can.1,2
The strategy is focused on communication techniques, and the high-level aspects of this strategy include the following: having the clinical trial discussion in a private location, and not, for example, in the middle of the infusion room where there is lack of privacy and also distractions. The patient should have people around her who will empower her and make the environment as emotionally supportive as possible. We should provide a pen and paper to the patient or a patient-designated attendee to write down facts and/or questions, explain the clinical trial as simply and understandably as possible, draw figures explaining the study and/or the mechanisms of action if necessary, allow the patient to ask as many questions she has, and do not push for the study but be balanced in the discussion. Additionally, honesty and directness are the best ways to answer patients if they ask you if you recommend a specific study or would you recommend a certain study if there is a choice, and these are really common requests. The efficacy and toxicities of study drugs are quite often not known, and these are the reasons why the trial is being done. Sometimes, trials will mandate many visits and blood draws, common for phase I studies, and these requests may or may not represent hardship for some patients. More than one meeting is necessary to discuss the study as well as risks and benefits and explain the treatment in the study. We also need to stress to the patient that trial participation is voluntary, and that she has the right to withdraw from the study at any point. The oncologist also needs to disclose any conflicts of interest they have and be prepared to answer the question from your patient if you would personally enroll in the trial or you would recommend the trial to one of your family members.
Dr. Sood: Ursula, this is good advice provided by the NIH. The principle of non-maleficence, or “do no harm,” also weighs heavily in this decision. Enrolling a patient in a clinical trial could expose them to potential harm, whether from side effects, unknown risks, or ineffective treatments. For a patient with a severe or terminal condition, a clinical trial might offer hope, but it also presents ethical questions if the trial fails to provide an improved outcome or worsens her quality of life. Physicians must also be cautious of any conflicts of interest, as they might be influenced by financial incentives, institutional pressures, or their own research interests when recommending clinical trials. Ensuring that patients are not being enrolled in trials for reasons other than their best interest is an important ethical obligation.
The ethical choice between recommending the standard of care and a clinical trial for a cancer patient is complex. Ethical decision-making in this context requires physicians to prioritize patient autonomy, provide clear and balanced information, and weigh the potential benefits and harms of each option. Ultimately, the patient’s values, preferences, and goals must guide the decision. The physician’s role is to act as an advisor and advocate, ensuring that the patient’s choice is informed, free from coercion, and aligned with their best interest.
Dr. Matulonis: Anil, I completely agree. Honesty here is so important, but also understanding the patient’s cancer and biology, what side effects should be avoided, and ultimately what the patient wants to do. We need to communicate to patients their treatment options which will sometimes include a study and sometimes not. If I don’t think a trial is the best option, I will tell them that. For example, if their cancer is actively growing and is predicted to be symptomatic very soon or is symptomatic, I will prioritize trials where clinical responses have been observed or where a predictive biomarker exists suggesting anti-cancer activity for this patient. Symptomatic or imminently symptomatic patients need the treatment to lead to an anti-cancer response quickly, regardless of whether the treatment is off study or on a clinical trial. The American Society of Clinical Oncology (ASCO) published a guideline in 2017 on patient-clinician communication which provides guidance on communicating with patients and provided some recommendations about clinical trials. The ASCO guideline recommended a particular sequence when discussing options: start with standard of care options and then move to a discussion of clinical trials. The ASCO guidelines also state that oncologists should make patients aware of all treatment options, including clinical trials and what the intent of the trial is, i.e. curative or palliative.
Dr. Matulonis: Anil, this has been a really great and important discussion.
Dr. Sood: Ursula, I agree–thanks for a very insightful discussion.
References:
1) NIH.gov
2) Eder M, Yamokoski A, Wittmann P, Kodish E. Improving informed consent: Suggestions from parents of children with leukemia. Pediatrics 2007;119;e849-e859.
3) Yap T, Yamokoski A, Noll R, Drotar D, Zyzanski S, Kodish E, A physician-directed intervention: Teaching and measuring better informed consent. Academic Med. Vol. 84, No 84, Aug. 2009.
4) Gillian T, Coyle N, Frankel RM et al. Patient-Clinician Communication: American Society of Clinical Oncology Consensus Guideline, Journal of Clinical Oncology 35: 3618-32, 2017.
Ursula Matulonis, MD is a medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts.
Anil K. Sood, MD is a gynecologic oncologist at MD Anderson Cancer Center in Houston, Texas.