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To better monitor and improve patient safety |
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To proactively identify patients in trouble |
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To compare populations across studies in a another way |
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To inform about outcome that are important to patients, which are measured poorly in other ways |
QOL and PRO endpoints can be informative even for small single arm studies, because the survey is started prior to treatment and the patient is therefore his or her own control.
That we are asking the patient about their experience shows that we care about them and are committed to following them carefully to identify needs and changes in their well being.
QOL endpoints may be particularly important to capture when the duration of treatment is long (e.g., many months or indefinitely until relapse) ... as a way to understand the impact of the treatment (including financial toxicities) on the patient's life.
As an endpoint there is the challenge of accounting for the placebo effect (our expectations influencing how we feel and what we report) and the influence of response to treatment (the tumor is visibly shrinking or growing) on how we feel.
In the future we might also use a standardized QOL tool as we would any laboratory test to monitor the patient for changes in perceptions about symptoms and side effects that can only be self-reported and as a way of monitoring for changes to overall quality of life - to guide in the care of the patient, such as for the need for emotional, social, or financial assistance.
See also Quality of Life
The need to make progress against cancers is urgent and is dependent on the conduct and completion of well-designed clinical trials. There is NO other way forward!
Clinical trials must have the potential to answer relevant clinical questions, while providing also a strong therapeutic rational for participation. By this I mean that study protocol (both if in a randomized allocation design) must have a potential to provide clinical benefit roughly equivalent or superior to available standard therapies, or the best supportive care.
Failing to meet the first requirement there is no purpose in doing the study. Failing to meet the second we have a high probability that the study will not complete enrollment, which means that some patients will have been exposed to risks for no benefit to society. Further, the conduct of poorly designed trials dilutes the pool of available participants, making it more challenging for better-designed studies to complete enrollment.
I have a traditional views about clinical trial design. I fully endorse the importance of randomized controls in many cases, and sufficient sample size in order to objectively assess efficacy and risks; and in the selection of eligible participants by criteria that reflect the population the therapy is ultimately intended to serve.
I am keenly interested in the discovery and validation of biomarkers that may be used as surrogates for clinical benefit to accelerate the assessment of future therapeutics that may help to individualize therapeutic decisions - helping patients to avoid unproductive toxicities, which can decrease the range of effective therapies that may be used later by the same patient.
I believe that the rationale for participation needs to be considered early and throughout the design process. Developing the rationale for a clinical study as a therapeutic decision requires insights and knowledge of best practice and the natural history of the disease in the various clinical settings. While this challenging task is best carried out by experts in the field, it must be communicated in an intelligible way to the would-be participants in order to be judged a reasonable alternative to standard therapies and to achieve a high level of informed consent.
Finally, while I have received training in the review of clinical trials from the FDA patient representatives program and from independent work, I am aware that as a layperson I will have gaps in my knowledge and therefore I will endeavor to provide input mainly from the perspective of the patient – who has the disease and is considering participation. Advocates must be good students of the disease, how it is treated, and also emerging investigational options.
Trial design - proposing the PCT as an alternative to the RCT
Karl Schwartz
Patients (all of us eventually) depend on industry AND publicly-sponsored trials
to reduce the burden of disease. It is NOT an either-or proposition
as some politically-oriented folks would have us think.
There's considerable overlap (cooperation) between industry - and taxpayer-funded clinical research as each will involve testing of commercially owned drugs - approved and investigational.
Patients depend on the industry-sponsored trials to test new drug products or new uses of approved drugs. Only the industry has the resources and ownership rights needed to provide manufacturing and distribution systems. This role is critical to ensure all patients have access to the drugs that demonstrate efficacy and win FDA approval. The testing of new drugs carries a very high financial risk (for investors) as many such trials fail to win marketing approval - an evaluation process that requires substantial time and sums of money. The financial risks are mitigated by patent law - allowing the company to have exclusive rights and to charge what the market will bear - allowing the companies to realize very high profits if they succeed. These benefits are provided to the company by public consensus (arguably and ideally) in order to encourage the development of better treatments ...in order to serve the public good. Without financial incentives and ownership rights drug development would not be done and patients would continue to die from medical conditions that have the potential to be treated effectively, such as demonstrated for HIV and many types of lymphoma.
The primary mission of any drug company is to maximize profits; so there will be an inclination to focus on trials that enhance that goal, and avoid sponsoring studies (or providing the study drugs) if the study outcome puts their for-profit mission at risk. The objective of maximizing profits is not a sin, it is simply a fact of life - the company's reason for being.There is so much of critical importance to patients to learn about how to use approved drugs. Much of this is not typically of interest to industry sponsors, such as how to identify the best dose and administration schedule of an antibody drug (RESORT), or how to identify up front which patents will benefit from the drug and who will experience only unproductive toxicity.
Further, the scientific insights and data gathered in publicly-funded studies is more likely to be shared and published - such as tests that may predict response to an approved treatment. Commercial entities may also be reluctant to sponsor trials (or provide the study drug) that compare their product to a competitor's in pick the winner trials - or to study treatments for uncommon medical conditions that have a low profit potential.Commercial drug products are not invented in a vacuum - the idea evolves or emerges from the larger body of scientific knowledge - including discoveries of treatment targets made by publicly-funded basic science. Commercial groups certainly play a role in scientific discovery, but the body of science is most accurately described as a public resource. Its validity and strength depends on peer review, on standards for scientific methods, on reporting to scientific journals, on regulatory review, and also very often on patient participation in clinical trials!
Virtually all publicly-funded therapeutic trials will require cooperation from the commercial sponsor - because they legally own the drug (developed or purchased it) and their study drug is not yet approved. (So like we learned in the schoolyard, the kid who owns the ball has veto power about the rules of the game.) So it's important to patients that we can efficiently identify shared goals and develop guidelines on the types of studies that are most appropriate for public funding. Here we will propose a list of attributes and .
We can think of cooperative group research as science … motivated to advance the common good, funded by the common man (taxpayers); and industry-research as that which is done for the purpose of generating a profit, funded by shareholders from any part of the globe.
Study type / attribute |
Funding |
Comment |
Study drug tested for common disease for purpose of winning market approval (registration trials) | Industry | The study will get done anyway; public will not share in the financial benefit. Public could benefit from correlative science and assays but only if published and shared. |
Study drug tested is part of induction and maintenance (not compared to another study drug) | Industry | A win-win situation for the company no matter which arm is superior; it will get done anyway; larger public will not share in the financial benefit. Public could benefit from correlative science and assays but only if published and shared. |
Study drug tested for orphan conditions or new subset of a disease based on biology of the disease | Public |
low market / profit potential |
Compare approved protocols already used in clinical practice when either is considered reasonable | Public | little industry incentive to compare effectiveness if they are profiting |
Pick the winner of multiple study drugs by different commercial sponsors to combine with approved agents | Public | little industry incentive to provide study drug unless there is no other clear path to testing it. |
Study involves evaluating a novel test having the potential to accelerate the evaluation other interventions | Public | potential to advance science and run other trials more efficiently |
Study drug tested in combination with approved protocol without compelling science about mechanism of action (synergy) or selecting patients | Industry | exploratory; unlikely to advance the science |
Study of promising new or existing compound with no interested or available commercial owner | Public | |
... more to come | ||
Notes from Publicly Funded Clinical Trials and the Future of Cancer Care Richard L. Schilsky, M.D. Professor and Chief Section of Hematology-Oncology University of Chicago Deputy Director, Comprehensive Cancer Center Optimize Treatment (drug registration) Create New Knowledge (expand market share) Improve Public Health (create shareholder value) Compare the effectiveness of various treatment options Combine/compare drugs developed by different sponsors Develop therapies for rare diseases Address optimal dosing Test multi-modality therapies such as radiation therapy in combination with drugs Identify patient and tumor subsets most likely to benefit from interventions Study screening and prevention strategies Focus on survivorship and quality of life Publish negative results Assess cost and cost-effectiveness Provide “gold standard” databases for registry studies Comparing Efficacy Compare Treatments from Different Sponsors “Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers and policy makers to make informed decisions that will improve healthcare at both the individual and population levels." Survival Comparing Laparoscopic-assisted Colectomy with Open Colectomy Rare Disease Treatments Optimize Dosing Combine Treatment Modalities Identify Patient Subsets Testing protocols in patient subsets: CALGB 9343: Impact of Breast RT in Older Women Receiving Tamoxifen Tackle practical problems: Most people who are diagnosed with cancer are elderly Most people who are on clinical trials of anti-cancer therapy are not elderly The risks and benefits of anti-cancer therapies in the elderly is uncertain Who Benefits from Adjuvant treatments Survival Comparing Laparoscopic-assisted Colectomy with Open Colectomy Publish Negative Results Assess Cost Effectiveness (for equivalent treatments) Provide Gold Standard Databases DFS According to Data Source SEER-Medicare Analysis of RT Use in Older Women Following Publication of C9343 Translational Science Infrastructure correlative science infrastructure Exploratory (Correlative) Biomarker Studies BRAF Mutation is Prognostic in Stage III Colon Cancer: CALGB 89803 Biomarker-Drug Co-Development PKC 412/FLT3 Mutation Analysis Co-Development CALGB 10603 Marker Validation Studies Cooperative groups have the capacity to conduct many types of biomarker studies, including formal validation trials Summary Publicly funded clinical trials are essential to: directly compare drug treatments; develop combined modality treatments; study chemoprevention and rare diseases; identify patient subsets; study health outcomes, cost and cost-effectiveness Creation of the National Clinical Trials Network National Clinical Trials Network (NCTN) provides essential infrastructure for publically funded trials in treatment, control, screening, diagnosis, and prevention NCTN provides a unified clinical and translational infrastructure for the extramural cancer community: investigators, patients, advocates, and industry NCTN efficiently functions to answer critical questions not well supported in a commercial environment NCTN will eventually replace the program we have known as the cooperative groups Risks of Replacing the Cooperative Groups Loss of institutional allegiance and cost sharing Fewer publically funded trials Loss of young investigator mentoring Loss of competition to drive innovation The NCTN becomes a research infrastructure but not a research engine Time will tell whether the NCTN is able to set new standards of care for cancer patients The future of cancer care depends on a robust, publically funded clinical trials system! |
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A link to my advocacy CV |
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Summary background for Karl Schwartz President and co-founder, Patients Against Lymphoma Patient representative: Alliance Cooperative Group, Lymphoma Committee (2012-2015) FDA Advisory Committee (2002- present) NCI Progress Review Group (~2002) NCI Biospecimen Best Practice Workshops (~2004) NCI Steering Committee - Lymphoma 2003- 2006 ASCO/AACR Workshop: Methods in Clinical Cancer Research - Patient Advocate Faculty NCI Centralized Institutional Review Board (at present) AACR / Stand Up to Cancer, Joint Scientific Advisory Committee ASCO - HIV Working Group Friends of Cancer Research Modernizing Eligibility Criteria Project for Modernizing Eligibility Criteria in Cancer Studies |
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On Ownership of an Investigational Drug PAL |
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On Pathways to Progress - 2014 |
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On Biomarkers - Draft: perspectives and resources PAL |
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On reasons for drug shortages, proposed solutions |
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On Rising Healthcare Costs ... Threatening Access to Quality Cancer Care PAL |
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On Testing Upfront therapy for indolent lymphoma |
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Proposing the Patient-selected Control Trial (PCT) PCT-Published-to-Lymphomation.pdf
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On Progression Free Survival: Is it the Right Endpoint for Judging the Clinical Benefit of Maintenance Rituxan following First Therapy for Indolent Lymphoma? One Advocate's perspective |
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On recipe for progress |
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On the basic elements for progress |
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On the format of Reporting Abstracts Abstract-perspective.PDF |
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On Finding & Evaluating Online Medical & Support Information
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On Giving Tissue and Blood - an advocate's perspective PDF |
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On Interest, attitudes, and participation in clinical trials among lymphoma patients with online access. JCO (fixed)
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Letter to FDA on Transparency initiative PDF |
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On Vaccines and Autism link:
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On Accelerated Approvals |
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Lymphomation Blog (under maintenance) |
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On Progression Free Survival: Does it predict better survival in Follicular Lymphoma? PDF |
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On FDA transparency PDF |
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On Radioimmunotherapy reimbursement policy 2009-CMS-letter.PDF |
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On Drug Reviews, Vaccine misinformation, Level of Evidence PAL |
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On statistics for lymphoma subtypes (letter to SEER) PAL seerltr.pdf
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Detailed Statistics for NHL http://bit.ly/SEER-NHL |
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Detailed Statistics for Hodgkins http://bit.ly/SEER-Hodkgins
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Guidance: Strategies for Finding and Evaluating Medical Information
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Guidance: How to evaluate medical claims and data
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10 Rules for Redesign of Our Health Care System - IOM ~ Crossing the Quality Chasm |
To help accelerate the development and evaluation of investigational therapies for lymphomas.
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Patient attitudes towards trials: Report from our Lymphoma Patient Survey regarding
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Perspective: Adaptive Design Conference, July 2006, Washington DC
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Perspective: Harmonizing Research Goals with Meeting the Clinical Needs
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Study Proposal: Combine molecular profiling research with evaluating first-line use of patient-specific idiotype cancer vaccines - studyprop.pdf
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Perspective: Advocating for Coordinated Immunotherapy Research
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"The patient is waiting" - patient perspectives on aspects of toxicity and the need for innovation - PAL
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Question: Radiofrequency Ablation for lymphoma? PAL |
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Clinical trial design and participation - We consult with Patients, the FDA, Drug Sponsors, the NCI, investigators, and community physicians. Our goal is to increase participation in order to accelerate progress against the disease. How else? |
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Advocacy? Radiofrequency Ablation for lymphoma? PAL |
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What Makes A Study Desirable - Known Obstacles to Accrual -
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TRIAL DESIGN: Patients Against Lymphoma Presentation
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Perspective: Bexxar Approval Petition Letter to the FDA
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Perspective: What can we do to responsibly accelerate drug evaluations |
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Perspective: Accelerated Approval for Low Toxic Therapies - Draft proposal to investigators & FDA |
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Perspective: The Progress Review Group plan - The PRG plan and why it needs to be carried out |
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Perspective: Letter to Mark McClellan, MD, PhD Commissioner, Food and Drug Administration
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Perspectives: Letter to CMS on proposed rate cuts for radioimmunotherapies Also:
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Resources compiled |
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State Coverage for Health Care Costs for Clinical Trials?
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Question: Are patients with indolent cancers receiving too many CT scans? Background information |
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The long-term risks associated with (repeated) CTs Appeals to the use of non-radioactive scans - Antonio M.C. Reis, M.D. and Maria de Lurdes F.V. Queimado, M.D., Ph.D. |
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A User’s Manual For The IOM’s ‘Quality Chasm’ Report - IOM
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