--- title: "PROs for Early Phase Oncology Dose Selection: Full Research" description: "Dropout rates of 15-30% in AOM trials threaten regulatory submissions. Evidence-based strategies to improve participant retention in anti-obesity trials." type: article version: 1 version_id: "ec9709bb-35f0-4dac-ab2b-12dfb90faa82" generated_at: "2026-06-19T14:13:51.086Z" author: "at least" date_published: "2026-06-19T11:51:29.000Z" date_modified: "2026-06-19T12:16:39.637Z" language: en reading_time: "13 min" word_count: 2479 keywords: ["PROs for Early Phase Oncology Dose Selection", "Full Research", "Key Points"] url: "https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection" --- # PROs for Early Phase Oncology Dose Selection: Full Research > Dropout rates of 15-30% in AOM trials threaten regulatory submissions. Evidence-based strategies to improve participant retention in anti-obesity trials. ## Key Takeaways - Key Points - AUTHOR BIO - Explore Our Content [Back to Resource Hub](https://signanthealth.com/resources) Article # PROs for Early Phase Oncology Dose Selection: Full Research [Signant Health](https://signanthealth.com/resources/author/signant-health) Jun 19, 2026 [ ](http://www.facebook.com/share.php?u=https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection&utm_medium=social&utm_source=facebook)[ ](http://www.linkedin.com/shareArticle?mini=true&url=https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection&utm_medium=social&utm_source=linkedin)[ ](https://twitter.com/intent/tweet?original_referer=https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection&utm_medium=social&utm_source=twitter&url=https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection&utm_medium=social&utm_source=twitter&source=tweetbutton&text=)[ ](mailto:?subject=Check%20out%20https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection&utm_medium=social&utm_source=email%20&body=Check%20out%20https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection&utm_medium=social&utm_source=email) [Article](https://signanthealth.com/resources/tag/article) Physicians systematically underreport treatment-related adverse events compared to participant self-reports, and that gap directly compromises dose selection decisions in early-phase oncology trials.   This peer-reviewed viewpoint, published in JMIR Cancer (Byrom, Everhart et al., 2025), co-authored across Signant Health, Sanofi, Orion Pharma, and University College London, sets out the clinical rationale, instrument selection framework, and electronic implementation strategy for structured participant-reported outcome assessment from first-in-human studies onward.  ## Key Points  - All 50 adverse events reported by at least 10% of participants in a published phase 1 study were consistently underreported by physicians using the CTCAE, with 9 events identified at least 50 times less frequently by clinicians than by participants themselves. - The FDA's August 2024 final guidance on optimizing dosage for oncological treatments requires characterization of dose-response relationships across efficacy and tolerability, not identification of maximum tolerated dose alone. - An organ system hierarchy approach to PRO-CTCAE administration, combined with free-text capture for unlisted symptoms, enables comprehensive adverse event coverage from first-in-human studies without pre-selecting items that may miss novel targeted therapy toxicities. - The full proposed weekly assessment package, including PRO-CTCAE organ system navigation, FACT GP5 or EORTC Q168 overall impact item, and EORTC QLQ-C30 physical and role function subscales, is estimated at under five minutes per week using smartphone ePRO administration with branching logic. - Electronic PRO collection via smartphone reduces missing data through automated reminders, eliminates data queries through branching logic, and enables at-home completion, removing clinic visit burden for participants managing serious illness. - The paper, published open access in JMIR Cancer (doi: 10.2196/64611), contains the complete statistical guidance, missing data considerations, instrument selection rationale, and implementation framework for sponsors building PRO strategy into early phase oncology programs.  **Why It Matters Now: Maximum Tolerated Dose Is No Longer a Sufficient Endpoint**  For a participant enrolled in an early-phase oncology trial, treatment participation is not a neutral act. They are managing a serious illness, attending visits, tolerating side effects, and in many cases accepting toxicity because the alternative is worse. When the dose they are receiving is higher than necessary to achieve efficacy, because the dose selection process did not capture their full symptom experience, the cost of that gap is borne by them directly.  The evidence that physicians miss this picture is not new, but it is consistent. Veitch and colleagues ([Journal of the National Cancer Institute, 2021](https://academic.oup.com/jnci/article/113/8/943/6146407)) found that all 50 adverse events reported by at least 10% of participants undergoing cancer treatment were underreported by physicians using the CTCAE.   A separate multi-center European study of 1,933 oncology participants (Laugsand et al., Health and Quality of Life Outcomes, 2010) found clinicians consistently underscored the severity of pain, fatigue, weakness, anorexia, and depression. When those gaps compound across a dose-escalation program, the recommended dose that emerges may not be the optimal one.  The FDA's August 2024 final guidance on optimizing dosage for oncological treatments formalizes the regulatory response to this problem. Twenty-six percent of FDA-approved kinase inhibitors between 2001 and 2015 required post-marketing commitments to study alternative doses, a figure that reflects the limitations of maximum tolerated dose approaches for targeted therapies with wide therapeutic indices. For sponsors designing early-phase programs today, that expectation is the starting point, not an aspiration.  **What the Paper Contains: Instrument Selection, Implementation, and the Electronic Case**  The barriers to PRO adoption in early-phase oncology trials are documented and legitimate. PROM selection guidance for early phase settings has been limited. Statistical power in small cohorts constrains interpretation. Adding questionnaire burden to participants already managing serious illness and frequent clinical visits requires justification that has not always been available.  This paper, co-authored by Bill Byrom and Anthony Everhart of Signant Health alongside Paul Cordero of Sanofi, Chris Garratt of Orion Pharma, and Tim Meyer of University College London, addresses each barrier directly and with specificity. The organ system hierarchy approach to PRO-CTCAE administration is described with reference to the branching logic that keeps weekly completion times under five minutes, drawing on published median per-item completion data of 6 to 14 seconds (Kalpadakis-Smith et al., Value in Health, 2023). The case for electronic over paper collection is argued on the grounds of missing data reduction, query elimination, and the practical infeasibility of complex branching logic in paper format. Missing data handling, sensitivity analyses, and the statistical interpretation of PRO tolerability data in small early phase cohorts are addressed with the nuance that a published peer-reviewed paper allows and that a summary document cannot replicate.  For sponsors and CROs at the protocol design stage for an early-phase oncology program, this paper provides the complete instrument selection and implementation rationale. The four-page summary available separately introduces the core argument for teams earlier in the evaluation process. > "It is necessary to build a PROM assessment strategy for early phase trials that combines elements of well-established scales to assess safety and tolerability in a package that is practical and not burdensome, yielding vital data to support decision-making as the trial progresses." - *Bill Byrom, PhD, Vice President, Product Intelligence and Positioning, Signant Health; JMIR Cancer, 2025*   > > * * * ### How does the paper address missing data in early phase PRO collection? The paper acknowledges that missing data handling is a critical consideration in early phase settings where researchers may use less formal interpretive approaches. It recommends sensitivity evaluations to assess the impact of missing data under different assumptions. Electronic PRO collection via smartphone mitigates missing data through automated reminders and remote monitoring and eliminates ambiguous entries through branching logic validation at the point of completion. ### Do informant interviews improve data quality in schizophrenia trials? Yes. Participants with schizophrenia frequently have poor insight, cognitive impairment, and guardedness that limits self-report accuracy. Informant interviews provide context that external reviewers need to validate PANSS ratings accurately. Recording both the participant and informant interview allows external raters to conduct complete evaluations, reducing variance and the time spent reconciling discrepancies between site and central ratings. ### How does blinded data analytics improve signal detection in schizophrenia trials? Blinded data analytics identify site-level rating patterns predictive of increased placebo response before they compromise study outcomes. Published peer-reviewed research co-authored by David Daniel, MD, demonstrates that erratic ratings predict placebo response in both negative symptom and acute schizophrenia trials, and that prospective identification of sites with erratic patterns, followed by remediation or exclusion from enrolment, improves drug-placebo separation at the study level. ## AUTHOR BIO  Name: Bill Byrom Title and Credentials: PhD, Vice President of Product Intelligence and Positioning at Signant Health  Bio: Bill Byrom, PhD, is Vice President of Product Intelligence and Positioning at Signant Health, specializing in ePRO methodology, PRO instrument development, and clinical outcome assessment strategy across oncology, CNS, and rare disease trials.   Co-authors on the paper are Anthony Everhart, MD (Signant Health), Paul Cordero, PhD (Sanofi), Chris Garratt, MBChB (Orion Pharma), and Tim Meyer, MBBS, PhD (University College London).   The paper was peer-reviewed by Arnold Degboe and Jay Tanna and edited by Naomi Cahill.  [READ THE FULL PAPER](https://signanthealth.com/hubfs/Marketing%20Assets/Articles/Article%20-%20Leveraging%20PROMs%20-%20JMIR%20-%20Byrom%20Everhart%20-%202025.pdf) Designing PRO strategy for an early-phase oncology program aligned with Project Optimus? [Speak to Bill Byrom, PhD](/contact-sales), or Anthony Everhart, MD, about instrument selection, ePRO implementation, and tolerability assessment for dose-finding trials.  ## Explore Our Content [ ](https://signanthealth.com/resources/why-do-schizophrenia-trials-fail-to-separate-drug-from-placebo) Video ### [Why Do Schizophrenia Trials Fail to Separate Drug from Placebo?](https://signanthealth.com/resources/why-do-schizophrenia-trials-fail-to-separate-drug-from-placebo) [ ](https://signanthealth.com/resources/can-a-10-item-panss-work-as-well-in-pediatric-trials) Article ### [Can a 10-Item PANSS Work as Well in Pediatric Trials?](https://signanthealth.com/resources/can-a-10-item-panss-work-as-well-in-pediatric-trials) [ ](https://signanthealth.com/resources/what-ecoa-data-does-a-vaccine-trial-actually-need-to-capture) Video ### [What eCOA Data Does a Vaccine Trial Actually Need to Capture?](https://signanthealth.com/resources/what-ecoa-data-does-a-vaccine-trial-actually-need-to-capture) ### Get notified on new marketing insights Here mention the benefits of subscribing --- ## Frequently Asked Questions ### How does the paper address missing data in early phase PRO collection? The paper acknowledges that missing data handling is a critical consideration in early phase settings where researchers may use less formal interpretive approaches. It recommends sensitivity evaluations to assess the impact of missing data under different assumptions. Electronic PRO collection via smartphone mitigates missing data through automated reminders and remote monitoring and eliminates ambiguous entries through branching logic validation at the point of completion. The paper acknowledges that missing data handling is a critical consideration in early phase settings where researchers may use less formal interpretive approaches. It recommends sensitivity evaluations to assess the impact of missing data under different assumptions. Electronic PRO collection via smartphone mitigates missing data through automated reminders and remote monitoring and eliminates ambiguous entries through branching logic validation at the point of completion. Do informant interviews improve data quality in schizophrenia trials? Yes. Participants with schizophrenia frequently have poor insight, cognitive impairment, and guardedness that limits self-report accuracy. Informant interviews provide context that external reviewers need to validate PANSS ratings accurately. Recording both the participant and informant interview allows external raters to conduct complete evaluations, reducing variance and the time spent reconciling discrepancies between site and central ratings. ### Do informant interviews improve data quality in schizophrenia trials? Yes. Participants with schizophrenia frequently have poor insight, cognitive impairment, and guardedness that limits self-report accuracy. Informant interviews provide context that external reviewers need to validate PANSS ratings accurately. Recording both the participant and informant interview allows external raters to conduct complete evaluations, reducing variance and the time spent reconciling discrepancies between site and central ratings. Yes. Participants with schizophrenia frequently have poor insight, cognitive impairment, and guardedness that limits self-report accuracy. Informant interviews provide context that external reviewers need to validate PANSS ratings accurately. Recording both the participant and informant interview allows external raters to conduct complete evaluations, reducing variance and the time spent reconciling discrepancies between site and central ratings. How does blinded data analytics improve signal detection in schizophrenia trials? Blinded data analytics identify site-level rating patterns predictive of increased placebo response before they compromise study outcomes. Published peer-reviewed research co-authored by David Daniel, MD, demonstrates that erratic ratings predict placebo response in both negative symptom and acute schizophrenia trials, and that prospective identification of sites with erratic patterns, followed by remediation or exclusion from enrolment, improves drug-placebo separation at the study level. ### How does blinded data analytics improve signal detection in schizophrenia trials? Blinded data analytics identify site-level rating patterns predictive of increased placebo response before they compromise study outcomes. Published peer-reviewed research co-authored by David Daniel, MD, demonstrates that erratic ratings predict placebo response in both negative symptom and acute schizophrenia trials, and that prospective identification of sites with erratic patterns, followed by remediation or exclusion from enrolment, improves drug-placebo separation at the study level. Blinded data analytics identify site-level rating patterns predictive of increased placebo response before they compromise study outcomes. Published peer-reviewed research co-authored by David Daniel, MD, demonstrates that erratic ratings predict placebo response in both negative symptom and acute schizophrenia trials, and that prospective identification of sites with erratic patterns, followed by remediation or exclusion from enrolment, improves drug-placebo separation at the study level. --- ## About This Content **Source:** [PROs for Early Phase Oncology Dose Selection: Full Research](https://signanthealth.com/resources/pros-for-early-phase-oncology-dose-selection) **Author:** at least **Published:** June 19, 2026 *This content is provided for informational purposes. Please visit the original source for the most up-to-date information.*