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Advocacy > Advocacy Perspectives

Patient Perspectives - commentary, proposals, and letters

Last update: 04/14/2014

TOPICS
What is the purpose of Research Advocacy?  | Perspectives on Trial Design 
 
Guidance for Patients and Caregivers | Urgency & UnityGuidance for the NCI, the Industry, and the FDA
Research Funding and Insurance
 | Perspectives - old and new  | Advocacy Tools and Background

New: 

Perspective on Quality of Life and Other Patient Reported Outcomes in Clinical Trials
Perspective on Industry versus Publicly-funded Research
Cuts in NCTN?

 See also
Perspectives and Advocacy Experiences

What is the Purpose of Research Advocacy?

Patients are the primary stakeholders in clinical research as it is the patient that must endure the disease and the inadequacies of existing therapies.  (Not the shareholders, the researchers, or the clinical investigators.)

We are the ones recruited for testing of the investigational therapies, which have unknown benefits and risks and which, in some cases, will ultimately be utilized by many of us.  It is we who lose the most when clinical trials do not meet enrollment goals and fail to answer the study question ... a common and tragic occurrence. 

Since we live with the disease and must choose between therapeutic options, we can offer insights that will not necessarily be recognized by medical professional such as:

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Unethical trial designs

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How patients and treating physicians will judge the protocol as a therapeutic decision

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Possible deficiencies in the informed consent document

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The significance of the study question or events that are measured to estimate clinical benefit

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Concerns with the enrollment criteria that may become unnecessary obstacles to enrollment or that may call into question how well the study findings will apply to the population with the disease. 

I wish to participate as an advocate because I feel that my motivations, experiences, and training make me uniquely qualified to provide the patient perspective in a positive way.

I am a caregiver to my spouse; she is an eighteen-year survivor of lymphoma. Together we have experienced the uncertainties of treatment decisions, the disappointments and successes - and have considered and participated in multiple clinical trials and therefore have first-hand experience with the clinical trial consent process. 

I also serve the lymphoma patient community on a daily basis, moderating support forums and updating our non-profit website resource in response to patient questions, which includes substantial information on clinical trials. 

My experience includes providing support and the review of studies for a broad range of lymphomas: low and high risk, indolent and aggressive, including types that are managed conservatively or that can have a rapid fatal clinical course if not cured. 

Perspective on the Use of Quality of Life (QOL) and other
Patient-Reported Outcomes (PRO) in Clinical Trials

There are two potential uses for Patient-reported Outcomes (PROs) in clinical trials and in regular practice. 

1) The first is to monitor the patients for significant changes in their overall status that would not otherwise be captured. 

2) The second is to measure and compare patient reported outcomes as endpoints in a clinical trial --  as a way to measure the effects of treatment that otherwise would not be accounted for by laboratory tests or scans.   

The terms PRO and QOL are sometimes used interchangeably and this seems to be a source of confusion and is perhaps contributing to the slow adoption of these measures of clinical outcomes.  

PROs might be thought of as way to capture information that is specific to a common symptom of the disease, or to an anticipated side effect of the study drug.

QOL instruments can also capture the patient's experience of pain or fatigue, but can provide valuable information about the whole patient (global changes) - such as changes to the patient's sense of well-being. 

An easy-to-use and score, standardized QOL instrument should be incorporated into all trials:

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To better monitor and improve patient safety
(e.g., test for need to reduce dose when indicators drop suddenly)

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To proactively identify patients in trouble
(e.g., are in danger of dropping out for safety / financial / social / physical / emotional reasons)

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To compare populations across studies in a another way
(e.g., QOL scores were comparable) …  and

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To inform about outcome that are important to patients, which are measured poorly in other ways
(e.g., pain, fatigue).    

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
 

Perspectives on Clinical Trial Design

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

   
Perspective on industry- versus publicly-funded trials (DRAFT)

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 invite comments and suggestions from visitors.

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!
 

Patient Advocacy Background and Experiences: 

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A link to my advocacy CV
bullet Summary for Karl Schwartz

President and co-founder, Patients Against Lymphoma
Patient representative:
Alliance Cooperative Group, Lymphoma Committee
FDA Advisory Committee
NCI
-Progress Review Group
-Biospecimen Best Practice Workshops
-Steering Committee - Lymphoma
-Centralized Institutional Review Board
Patient Advocate Faculty ASCO/AACR Workshop:
Methods in Clinical Cancer Research
Stand Up to Cancer, Joint Scientific Advisory Committee


Advocate Perspectives - old and new:

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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

Web version: Trial design - proposing the PCT as an alternative to the RCT

On Good Science and Good Medicine
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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
 Slides: http://www.lymphomation.org/find-eval-final.PDF 

Teleconference presentation for Nurses and Social workers:
Sponsored by Lance Armstrong Foundation,
Leukemia and Lymphoma Society, July 2009
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On Interest, attitudes, and participation in clinical trials among lymphoma patients with online access.    JCO  (fixed)

Our
study published: ASCO 2009: 
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Letter to FDA on Transparency initiative PDF
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On Vaccines and Autism link:
It's easy to confuse correlation with causation - Tony L. Hines
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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 

The SEER website has improved, but the utility of the statistics for non-Hodgkin's lymphomas continue to suffer because subtypes of the disease are not yet provided.

UPDATE FROM SEER:
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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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On Abigail Petition - Compassionate Use Proposal
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Letter to researcher: Dr. Rosenberg
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On AACR Molecular  Targets and Cancer Therapeutics 2005
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On Biobank Best Practices
Patient Perspectives on the issue of transfer of  tissue for clinical use – particularly for use in translational clinical research - PDF 

"we may not have fully considered that requests for transfer of tissue for clinical use could many times be in harmony with the ultimate objective of achieving “personalized medicine,” and the oft-stated principle of  “partnering with patients”  – particularly when used to determine eligibility for clinical trials."

 

GUIDANCE: For Patients and Caregivers:

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Guidance: Strategies for Finding and Evaluating Medical Information
 
As presented at Gilda's Club Delaware Valley, April 2006
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Guidance: How to evaluate medical claims and data
 
Is this strong or weak information? Who is saying it?  It is reproducible?  Is it free of bias? ...
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10 Rules for Redesign of Our Health Care System - IOM ~ Crossing the Quality Chasm

 

URGENCY & UNITY

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PAL's Mission
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Commentary on AACR Molecular  Targets and Cancer Therapeutics 2005
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Why we need the National Biospecimen Network
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Recipe for Progress Against Lymphoma
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OFF - Oneness, Fairness, Focus Rationale for a united effort
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Our Fight is Similar - fighting cancer and terrorism - Patient perspectives

 

GUIDANCE: For the NCI, the Industry, and the FDA

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 
interest and participation in clinical trials  PDF
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Perspective: Adaptive Design Conference, July 2006, Washington DC 

Harmonizing Research Goals with Meeting the Clinical Needs of the Participants 
(slides with narrative) PDF
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Perspective: Harmonizing Research Goals with Meeting the Clinical Needs 
of the Participants - Apr 2006 - PDF 

Presentation at Favrille Investigators Conference
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Study Proposal:  Combine molecular profiling research with evaluating first-line use of patient-specific idiotype cancer vaccines - studyprop.pdf

Update: No longer feasible given the disappointing outcomes from vaccine phase III trials.
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Perspective:  Advocating for Coordinated Immunotherapy Research 

Eliminating Suffering and Death Due to Cancer by 2015: The Future of Cancer Research - 
Let's not forget Immunotherapy! - A letter to Dr. Von Eschenbach
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"The patient is waiting" - patient perspectives on  aspects of toxicity and the need for innovation - PAL
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an appeal for NBN in a brochure format PDF
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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 - 
Patient Perspectives on Clinical Trial Design
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TRIAL DESIGN: Patients Against Lymphoma Presentation 
Cancer Vaccine Conference, Boston - April 2003

Harmonizing Research and Treatment Goals Web version 
Color PDF or B&W PDF PDF versions  PDF-Help
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WHEN? Expedite Gene Profiling - Routinely snap freeze lymphoid tissue at biopsy
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WHEN? Rationale for the National Biospecimen Network NBN

There's an urgent need for new approaches and tools to accelerate clinical research, such as the National Biospecimen Network.  One reason that even well-controlled studies fail to provide definitive answers, it seems, is they are often unable to account for underlying biological differences in the tumors and patients.
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Perspective: The Need for Content and Structure Standards for Published abstracts
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Perspective: Changing the Treatment Paradigm for indolent NHL: treat early with novel agents?
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Perspective Patient Access to Emerging Therapies  for Incurable Cancers 
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Perspective: Bexxar Approval Petition Letter to the FDA 

Update: The ODAC has since recommended the approval of Bexxar and FDA has approved it.
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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 

Commentary on Abigail Petition - Compassionate Use Proposal
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Perspectives:  Letter to CMS on proposed rate cuts for radioimmunotherapies Also:
Patient-driven | What's at Stake | We're not asking for charity |
Your Help is Needed | Will Washington Sentence Lymphoma Patients to Death? 

FUNDING AND INSURANCE COVERAGE

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State Coverage for Health Care Costs for Clinical Trials? 
How Does Your State Measure Up?

CT SCANS

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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.

 

Resources & Research News

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A User’s Manual For The IOM’s ‘Quality Chasm’ Report - IOM
 
"the Quality Chasm report has attracted much less public attention than "To Err Is Human" did, but for the serious student of health care quality and the serious leader of needed change, it signals the possible dawning of a new and persistent sense that the U.S. health care system’s performance in many dimensions, not just safety, is unacceptably far from what it should be."
 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.