Oncologists' reflections on patient rights and access to compassionate use drugs: A qualitative interview study from an academic cancer center.

The U.S. Food and Drug Administration (FDA) allows patients with serious illnesses to access investigational drugs for "compassionate use" outside of clinical trials through expanded access (EA) Programs. The federal Right-to-Try Act created an additional pathway for non-trial access to experimental drugs without institutional review board or FDA approval. This removal of oversight amplifies the responsibility of physicians, but little is known about the role of practicing physicians in non-trial access to investigational drugs. We undertook semi-structured interviews to capture the experiences and opinions of 21 oncologists all with previous EA experience at a major cancer center. We found five main themes. Participants with greater EA experience reported less difficulty accessing drugs through the myriad of administrative processes and drug company reluctance to provide investigational products while newcomers reported administrative hurdles. Oncologists outlined several rationales patients offered when seeking investigational drugs, including those with stronger health literacy and a good scientific rationale versus others who remained skeptical of conventional medicine. Participants reported that most patients had realistic expectations while some had unrealistic optimism. Given the diverse reasons patients sought investigational drugs, four factors-scientific rationale, risk-benefit ratio, functional status of the patient, and patient motivation-influenced oncologists' decisions to request compassionate use drugs. Physicians struggled with a "right-to-try" framing of patient access to experimental drugs, noting instead their own responsibility to protect patients' best interest in the uncertain and risky process of off-protocol access. This study highlights the willingness of oncologists at a major cancer center to pursue non-trial access to experimental treatments for patients while also shedding light on the factors they use when considering such treatment. Our data reveal discrepancies between physicians' sense of patients' expectations and their own internal sense of professional obligation to shepherd a safe process for patients at a vulnerable point in their care.

A Yet Unrealized Promise: Structured Advance Care Planning Elements in the Electronic Health Record.

Background: Electronic health records (EHRs) may help enable reliable, rapid data management for many uses, such as facilitating communication of advance care planning (ACP). However, issues with validity and accuracy of EHRs hinder the use of ACP information for practical applications. Design: We present a cross-sectional pilot study of 433 older adults with cancer from three large health care systems, participating in an ongoing multisite pragmatic trial (4UH3AG060626-02). We compared data extracted from dedicated structured EHR fields for ACP to a chart review of corresponding ACP documentation contained in the medical chart. Results: Structured ACP data existed for 43.2% of patients and varied by site (25.7% -48.9%). Of the identified structured ACP data elements, 59.2% of recorded elements were correct, 23.7% were incorrect, and 17.1% were duplicates with heterogeneity across sites. Conclusion: Structured ACP data in EHRs were frequently incorrect. This represents a problem for patients and their families, as well as quality improvement and research efforts. Clinical Trials Registration: NCT03609177.

Conversations on Cancer Chemotherapy Cessation in Patients With Advanced Cancer: Qualitative Findings From a Multi-Institutional Study.

PURPOSE: As many as 20% of oncology patients receive chemotherapy in the last 14 days of their lives. This study characterized conversations between patients and cancer clinicians on chemotherapy cessation in the setting of advanced cancer. METHODS: This 3-site study captured real-time, audio-recorded interviews between oncology clinicians and patients with cancer during actual clinic visits. Audio-recordings were reviewed for discussion of chemotherapy cessation and were analyzed qualitatively. RESULTS: Among 525 recordings, 14 focused on stopping chemotherapy; 14 patients participated with 11 different clinicians. Two types of nonmutually exclusive conversation elements emerged: direct and specific elements that described an absence of effective therapeutic options and indirect elements. An example of a direct element is as follows: "…You know this is…always really tough…But I-I think that you may need more help…I think we're close to stopping chemotherapy…And hospice is really helpful to have in place…" In contrast, the second conversation element was more convoluted: "…transplant is not an option and surgery is not an option…The options…are taking a pill…It doesn't shrink the tumor…It may help you live a little longer. But I'm worried if [you] had the pill, it's still a therapy and it still has side effects. I [am] worried if I give it to you now, that you're so weak, it will make you worse." No relationship seemed apparent between conversation elements and chemotherapy cessation. CONCLUSIONS: Conversations on chemotherapy cessation are complex; multiple factors appear to drive the decision to stop.

"I Think It's Been Met With a Shrug:" Oncologists' Views Toward and Experiences With Right-to-Try.

BACKGROUND: The federal Right-to-Try (RTT) Act created an alternate regulatory pathway for preapproval access to investigational drugs. A few studies have examined the experiences of physicians with the Food and Drug Administration's Expanded Access Programs, but to our knowledge, no study has yet to examine their attitudes and experiences toward RTT. METHODS: This study explored the views of 21 oncologists at a major cancer center with 3 main sites across the United States using semi-structured interviews and qualitative analysis. Participants were selected to have experience with Expanded Access Programs. RESULTS: Most oncologists had limited familiarity with RTT, and several reported confusion about the legislation, including whether patients have a right to investigational drugs and an obligation for companies to provide them. Although oncologists were interested in decreased regulatory burdens, 3 areas of concern were articulated: lack of safety and oversight, unclear structure and no provision for data collection, and potential heightening of patient expectations. Only 4 oncologists had experience discussing RTT, and none formally attempted to obtain the drug through this mechanism. Participants questioned the practicality of RTT legislation and suggested alternative ways to improve access. CONCLUSIONS: The study provides foundational empirical data underlying challenging ambiguities by experienced oncologists familiar with off-trial use of investigational therapeutics and reaffirms the role of physicians and regulatory bodies in mitigating the risks of investigational drugs. Our findings highlight the need for medical centers to inform oncologists about RTT and other preapproval pathways so that they are able to address questions from patients interested in nontrial investigational drugs.

Incidence of Hypocapnia, Hypercapnia, and Acidosis and the Associated Risk of Adverse Events in Preterm Neonates.

BACKGROUND: Permissive hypercapnia is a lung-protection strategy. We sought to review our current clinical practice for the range of permissive hypercapnia and identify the relationship between PaCO2 and pH and adverse outcomes. METHODS: A secondary analysis of a delayed cord-clamping clinical trial was performed on all arterial blood gas tests in the first 72 h in infants < 32 weeks gestational age. All arterial blood gas values were categorized into a clinical range to determine the percent likelihood of occurring in the total sample. The univariate and multivariate relationships of severe adverse events and the time-weighted PaCO2 , fluctuation of PaCO2 , maximal and minimal PaCO2 , base excess, and pH were assessed. RESULTS: 147 infants with birthweight of 1,206 ± 395 g and gestational age of 28 ± 2 weeks were included. Of the 1,316 total samples, < 2% had hypocapnia (PaCO2 <30 mm Hg), 47% were normocapnic (PaCO2 35-45 mm Hg), 26.5% had mild hypercapnia (PaCO2 45-55 mm Hg), 13% had moderate hypercapnia (PaCO2 55-65 mm Hg), and 6.5% had severe hypercapnia (PaCO2 ≥ 65 mm Hg). There were no adverse events associated with hypocapnia. Subjects with death/severe intraventricular hemorrhage had a higher mean PaCO2 of 52.3 versus 44.7 (odds ratio [OR] 1.16, 95% CI 1.04-1.29, P = .006), higher variability of PaCO2 with a standard deviation of 12.6 versus 7.8 (OR 1.15, 95% CI 1.03-1.27, P = .01), and a lower minimum pH of 7.03 versus 7.23 (OR 0, 95% CI 0-0.06, P = .003). There was no significant difference in any variables in subjects who developed other adverse events. CONCLUSION: The routine targeting of higher than normal PaCO2 goals may lead to a low incidence of hypocapnia and associated adverse events. Hypercapnia is common, and moderate hypercapnia may increase the risk of neurologic injury and provide little pulmonary benefit.