Variations in patient-reported outcome (PRO) collection and reporting in novel FDA approved anticancer therapies.

e18202 Background: Patient-reported outcomes (PROs) are increasingly valued as a key tool in patient-focused treatment decisions. However, a lack of standardization leads to significant variability in PRO collection and reporting in ground-breaking clinical trials of novel agents. We sought to characterize the mechanisms of assessment and variability by which PROs are reported for newly approved anti-cancer therapies. Methods: We reviewed the U.S. Food and Drug Administration (FDA) approvals between 2011 and 2017 for anti-cancer new molecular entities (NMEs) and new biologic approvals (BLAs). For each therapy, the pivotal clinical trial leading to FDA approval was identified using the national clinical trial (NCT) number and assessed for inclusion of PROs. A separate PubMed search was conducted to evaluate for PRO publication distinct from the original trial based on national clinical trial registry number. Results: From 2011 to 2017, the FDA approved 66 NMEs/BLAs based on 74 clinical trials for cancer treatment. Of the 74 clinical trial publications, 21 (28%) of the trials published PRO data in their original clinical publication, 18 (24%) published a separate PRO analysis, and 35 (47%) did not publish PRO data in either format. Among the 32 clinical trials (43%) that listed PROs as pre-specified outcomes, 72% published PROs (23/32). The separate PRO analyses (N = 18) were published considerably later following FDA approval (mean 605 days) than the original clinical trials (mean 20 days, N = 74, P < 0.001). Conclusions: As cancer treatment options expand, therapy decisions become increasingly nuanced. PROs assist decision-making by providing detailed information on important aspects of quality of life and tolerability. Our research has identified a significant lag in the publication of companion studies of PRO data associated with pivotal clinical trials, representing a meaningful gap in information critical to patients and oncologists in the process of making informed decisions.

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Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms21207575 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7575 ◽

Cited By ~ 1

Author(s):

Shruti S. Sawant ◽

Suyash M. Patil ◽

Vivek Gupta ◽

Nitesh K. Kunda

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Treatment Options ◽

Current Treatment ◽

Genetically Engineered ◽

Cancer Therapies ◽

Anti Cancer ◽

Tumor Environment ◽

Systemic Side Effects ◽

Hypoxic Tumor

Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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The Psoriasis Symptom Inventory: An Effective Patient-reported Outcome Measure of Psoriasis Severity

The Journal of Rheumatology ◽

10.3899/jrheum.150127 ◽

2015 ◽

Vol 42 (6) ◽

pp. 1034-1036 ◽

Cited By ~ 6

Author(s):

Philip J. Mease

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Clinical Practice ◽

Severity Index ◽

Patient Reported Outcome ◽

Measurement Instruments ◽

Symptom Inventory ◽

Clinical Registries ◽

Patient Reported ◽

Psoriasis Severity

There is a need for simple, practical, and reliable measurement instruments for use in clinical trials, registries, and clinical practice to assess psoriasis severity and the change in symptoms with treatment. The Psoriasis Area and Severity Index (PASI) is the standard measure of psoriasis used in clinical trials, but it is rarely used in clinical practice and it is not readily used in clinical registries because of its complexity. The Physician Static Global Assessment score is a simpler measure also used in clinical trials and less frequently in registries and practice, but like the PASI, it requires some degree of experience to score. The Psoriasis Symptom Inventory (PSI) was developed as a simple measure to enable patients to self-score psoriasis severity. It has been demonstrated to be reliable and discriminative, and it correlated with the PASI score in a psoriasis clinical trial. It also was recently validated to assess psoriasis in a psoriatic arthritis (PsA) clinical trial. The PSI may be a useful and practical measure of psoriasis severity in psoriasis and PsA clinical trials, registries, and in clinical practice.

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Advance of Novel Coronavirus Registration Clinical Trial

10.1101/2020.03.16.20034934 ◽

2020 ◽

Author(s):

Gao Song ◽

Meng Qun Cheng ◽

Xian Wen Wei

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Treatment Options ◽

Descriptive Analysis ◽

Clinical Trial Registry ◽

Chi Square ◽

Plasma Therapy ◽

Study Duration ◽

Design Characteristics ◽

Novel Coronavirus

AbstractBackgroundTo analyze the characteristics and heterogeneity of clinical trials of Novel Coronavirus(COVID-19) registered in the China Clinical Trial Registry (ChiCTR), and provide data bases and information references for clinical treatmentMethodsStatistics of COVID-19 clinical trials registered with ChiCTR as of February 24, 2020 were collected. Descriptive analysis of registration characteristics. The chi-square test is used to compare statistical differences between different study types, intervention methods, study stage, and Primary sponsor.Results232 COVID-19 studies registered at the ChiCTR were collected. The overall number of COVID-19 registrations was increased. Hubei Province, China has the largest number of registrations. There were significant differences between the number of participants(P=0.000), study duration(P=0.008), study assignment(P=0.000), and blind method(P=0.000) for different study types. Significant differences could be seen in the dimensions of multicenter study(P=0.022), of participants numbe(P=0.000), study duration(P=0.000) and study assignment(P=0.001) for the four intervention methods. There were significant differences in study assignment(P=0.043) between the early and late studies. CMT drugs with high research frequency are chloroquine, lopinavir / ritonavir, and I-IFN; BI was Cell therapy, plasma therapy, Thymosin, and M/P-AB.ConclusionsDifferent study design characteristics have led to significant differences in some aspects of the COVID-19 clinical trial. Timely summary analysis can provide more treatment options and evidence for clinical practice.

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Feasibility of integrating the Outcomes4Me smartphone navigation application into the care of breast cancer patients (FIONA).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.1570 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 1570-1570

Author(s):

Steven J. Isakoff ◽

Maya Said ◽

Agnes H. Kwak ◽

Eva Glieberman ◽

Amanda Stroiney ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Clinical Trials ◽

Pilot Study ◽

Patient Engagement ◽

Medical Center ◽

Treatment Options ◽

Academic Medical Center ◽

Patient Reported ◽

Clinical Trial Information

1570 Background: Patients diagnosed with breast cancer (BC) face complex decisions about their care and many studies have shown that improved patient engagement results in increased satisfaction and better outcomes. Patient engagement includes education, treatment option selection, symptom tracking and reporting, and clinical trial opportunities. We conducted a pilot study to determine the feasibility of introducing the Outcomes4Me patient engagement app into the standard of care experience of BC patients. Methods: This was a pilot study (NCT04262518) conducted at an academic medical center. Eligible patients had any subtype of stage 1-4 BC and were on any type of chemo-, hormonal-, targeted-, or radiation-therapy for BC during the study period. Participants downloaded the app on their smartphone and their app usage was evaluated. Surveys were administered at baseline and end of study. Clinicians caring for patients using the app were surveyed at the end of the study. The primary endpoint was feasibility, defined as at least 40% of patients engaging with the app at least 3 times over the 12-week study period. Additional endpoints included usability, satisfaction, correlation of patient reported data with the EHR, clinical trial matching, and patient experience. Results: Between June 2020 and December 2020, 107 patients enrolled; results are reported for 90 patients with complete data as of 1/24/21. Baseline demographics: median age 53 (range: 27-77); 90% White, 4% Black, 3% Asian; 66% had hormone positive/HER2-, 20% HER2+, and 13% triple negative BC; 31% had stage 4 disease. At study entry, 93% had never used an app to help with their disease or treatment options. Over the 12 week study period, 58% of patients engaged with the app at least 3 times, meeting the primary feasibility endpoint. Patients engaged with the app on average 5.5 days (range: 0-40) with 20% engaging on more than 10 days during the study. The mean System Usability Score was 71 (median = 76) and was similar across age groups. The 5 app features deemed most (‘somewhat’ or ‘very’) helpful were: background about their BC (76%), information about treatment options (74%), newsfeed about their BC (70%), symptom tracking (65%), and clinical trial information (65%). 53% said that the app helped them keep track of symptoms and 33% said they are more likely to explore or enroll in a clinical trial after using the app. Conclusions: Integration of the Outcomes4Me app into the care management of BC patients is feasible with acceptable usability. Our results suggest that use of a patient smartphone app may be helpful for many aspects of patient education and engagement for patients with BC. The results also suggest that this type of intervention can help patients better track their symptoms and make them aware of clinical trials, potentially facilitating the management of side effects and accelerating clinical trials recruitment. Clinical trial information: NCT04262518.

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Patient-reported outcome instruments in clinical trials of systemic sclerosis

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198319886496 ◽

2019 ◽

Vol 5 (2) ◽

pp. 90-102 ◽

Cited By ~ 3

Author(s):

John D Pauling ◽

Joana Caetano ◽

Corrado Campochiaro ◽

Giacomo De Luca ◽

Ana Maria Gheorghiu ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Systemic Sclerosis ◽

Patient Reported Outcome ◽

Future Research ◽

Valuable Insight ◽

Surrogate Outcome ◽

American College Of Rheumatology ◽

Patient Reported ◽

And Performance

Patient-reported outcome instruments provide valuable insight into disease-related morbidity known only to the patient and complement more objective outcome tools in the clinical trial setting. They are of particular importance in systemic sclerosis owing to the challenges around defining disease activity, the episodic nature of many disease-specific manifestations and the paucity of validated objective surrogate outcome measures for use in clinical trials. Early clinical trials of systemic sclerosis often incorporated legacy patient-reported outcome instruments, but the last 20 years has witnessed the emergence of several scleroderma-specific instruments that are now being routinely used alongside other outcomes in systemic sclerosis clinical trials. More recently, the value of patient-reported outcomes has been highlighted by their prominence in the American College of Rheumatology Combined Response Index for Systemic Sclerosis that has been utilized as the primary endpoint of recent clinical trials of early diffuse systemic sclerosis. This review considers the role and performance of the various patient-reported outcome instruments utilized in systemic sclerosis clinical trials, the current positioning of patient-reported outcome instruments within clinical trial endpoint models across the range of systemic sclerosis disease manifestations and, where applicable, we shall highlight areas for future research.

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Lessons Learned from Conducting Internet-Based Randomized Clinical Trials During a Global Pandemic

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa602 ◽

2020 ◽

Author(s):

Matthew F Pullen ◽

Katelyn A Pastick ◽

Darlisha A Williams ◽

Alanna A Nascene ◽

Ananta S Bangdiwala ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Clinical Trial Design ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Lessons Learned ◽

Online Data ◽

Global Pandemic ◽

Patient Reported

Abstract As the SARS-CoV-2 pandemic evolved, it was apparent that well designed and rapidly conducted randomized clinical trials were urgently needed. However, traditional clinical trial design presented several challenges. Notably, disease prevalence initially varied by time and region, and the pockets of outbreaks evolved geographically over time. Coupled with an occupational hazard from in-person study visits, timely recruitment would prove difficult in a traditional in-person clinical trial. Thus, our team opted to launch nationwide internet-based clinical trials using patient-reported outcome measures. In total, 2795 participants were recruited using traditional and social media, with screening and enrollment performed via an online data capture system. Follow-up surveys and survey reminders were similarly managed through this online system with manual participant outreach in the event of missing data. Here, we present a narrative of our experience running internet-based clinical trials and provide recommendations for the design of future clinical trials during a world pandemic.

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Adapting preference-based utility measures to capture the impact of cancer treatment-related symptoms

The European Journal of Health Economics ◽

10.1007/s10198-021-01337-6 ◽

2021 ◽

Author(s):

Koonal K. Shah ◽

Bryan Bennett ◽

Andrew Lenny ◽

Louise Longworth ◽

John E. Brazier ◽

...

Keyword(s):

Cancer Treatment ◽

De Novo ◽

Patient Reported Outcome ◽

Cancer Therapies ◽

The Core ◽

Transient Nature ◽

Patient Reported ◽

Value Sets ◽

The Impact ◽

Utility Measures

AbstractIt is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation.

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Looking Ahead: Visual and Anatomical Endpoints in Future Trials of Diabetic Macular Ischemia

Ophthalmologica ◽

10.1159/000515406 ◽

2021 ◽

Author(s):

Chui Ming Gemmy Cheung ◽

Elizabeth Pearce ◽

Beau Fenner ◽

Piyali Sen ◽

Victor Chong ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Foveal Avascular Zone ◽

Consensus Definition ◽

Clinical Trial Endpoints ◽

Patient Reported ◽

Trial Endpoints ◽

Macular Ischemia

Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

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Clinical trial design for cutaneous neurofibromas

Neurology ◽

10.1212/wnl.0000000000005790 ◽

2018 ◽

Vol 91 (2 Supplement 1) ◽

pp. S31-S37 ◽

Cited By ~ 5

Author(s):

Ashley Cannon ◽

Kurt Jarnagin ◽

Bruce Korf ◽

Brigitte C. Widemann ◽

Denise Casey ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Trial Design ◽

Skin Diseases ◽

Clinical Trial Design ◽

Patient Reported Outcome ◽

Clinical Development ◽

Patient Reported ◽

Intervention Patient ◽

Cutaneous Neurofibromas

ObjectiveSeveral clinical trials targeting cutaneous neurofibromas (cNF) have been conducted; however, none has resulted in meaningful changes to care. The Clinical Trial Design and Development subgroup's goals were to (1) define key considerations in the design of clinical trials for cNF, (2) summarize existing data in relation to these considerations, and (3) provide consensus recommendations about key elements of trial design to accelerate the clinical development of therapies for cNF.MethodsThe subgroup, with experts from genetics, dermatology, neurology, oncology, and basic science, spanning academia, government research, and regulatory programs, and industry, reviewed published and unpublished data on clinical trials for cNF and other diseases in the skin. Discussions of these data resulted in formulation of a list of priority issues to address in order to develop efficient and effective clinical trials for cNF.ResultsThe subgroup identified 2 natural history studies of cNF, 4 priority outcome measures, and 6 patient-reported outcome tools for potential use in efficacy trials of cNF. Time to initiate intervention, patient eligibility, mechanism of action, route of administration, safety monitoring, and regulatory agency interactions were identified as key factors to consider when designing clinical trials for cNF.ConclusionsAlignment on endpoints and methods for the measurement and quantification of cNF represent a priority for therapeutic development for cNF. Advances in technological methods and outcome tools utilized in other skin diseases may be applicable to cNF studies. Patient age is an important factor guiding trial design and clinical development path.

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Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS

Trials ◽

10.1186/s13063-021-05113-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhuoran Kuang ◽

◽

Xiaoyan Li ◽

Jianxiong Cai ◽

Yaolong Chen ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Secondary Outcome ◽

Specific Information ◽

Clinical Trial Registry ◽

Data Set ◽

Diagnosis Criteria

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

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