Advocacy > Advocacy Perspectives

Patient Perspectives - commentary, proposals, and letters

Last update: 05/11/2016

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

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

New:   Lessons Learned in CLL  | Giving Tissue and Blood | "Consent" for unspecified future use?

 See also Perspectives and Advocacy Experiences

Why Research Advocacy?

To contribute and influence thought leaders and the design of clinical studies, research advocates need to be ardent students of the disease --  well-informed about regular practice and with emerging approaches to treating the disease. 

While it's possible for laypersons to achieve standing and be heard by investigators, it takes a good amount of time and study.  Presently there are no formal "career" pathways to follow.  We advocates learn from other advocates, and by doing it - pushed by our desire to advance progress against the disease.  We need also, like the best scientists, to know what we do not know.

Patients and caregivers are the primary stakeholders in clinical research as we must endure the disease and the inadequacies of existing therapies. As Chaya once quipped:  "We have the most skin in the game" (Not the drug sponsor or shareholders, not the researchers or the clinical investigators).

Patients 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.   We lose the most from siloed research that fails to add to the body of scientific knowledge, or change practice, or make future research more efficient.

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

	Anticipating how patients and referring physicians will judge the protocol as a therapeutic decision (accrual)
	Citing deficiencies in the informed consent document or process (ethics)
	The urgent need to standardize biospecimen capture, analysis, and reporting  (generalizability) The need to make future studies more efficient by validating surrogate markers for efficacy and safety.
	The significance of the study question or events that are measured (appropriate - non-ambiguous endpoints)
	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.  (generalizability)

I am a caregiver to my spouse; she is an twenty-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. 

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

"Consent" for unspecified future use?

The source of the discussion is my talk on giving blood and tissue http://bit.ly/1u9zv9h 

Specifically it’s on an ownership perspective, slide 9:
An advocate’s perspective on the “ownership” of patient-derived biospecimens

• That researchers and medical institutions are stewards of patient biospecimens (not owners)
• That the biospecimens that patient’s have taken risks to give will be maintained and protected for optimal research use.
• That requests for biospecimen transfer (e.g., tissue blocks) from one accredited institution to another should be granted when the patient gives consent

Mine is not a particularly radical perspective but it appears to go against the default policies of many institutions (based on personal experiences and recent investigator comments). Bioethicists have long cited the inadequacies of consent for unspecified future use - it's just not possible for it to be truly informed because we cannot anticipate future uses. Further, the devastated patient receiving a cancer diagnosis is not absorbing or considering all of the implications of a surgical consent.

Most commonly giving consent for unspecified future use is optional and the consent document is boilerplate.

Institutional policies and consents seem remnants of a time when the utility of patient samples was limited to in-house laboratory studies. The choice was between discarding it as waste material or using it in a lab to train future scientists (which is a great use of it).

Today, the information in our cells (DNA) can potentially tell researchers about our predispositions to disease ... not just for ourselves but our families. Sometimes the findings – if inappropriately linked to our clinical information (perhaps still unlikely but increasingly possible) can be stigmatizing - for example, our familial risk for alcoholism, drug addition, dementia can be revealed with correlative research on our cells.

Correlative science by definition requires also annotation that includes our clinical history in order to be useful - to be correlated with something ... including our demographics (race, age, sex, ... ) so it's important that future use of annotated samples be de-identified (coded) to protect our confidentiality and stored on IT systems with strong security measures in place. Was this described in the consent you signed prior to surgery? Probably you do not even remember. Probably it was boilerplate and not specific to the systems of the institution you happened to go to for surgery (by convenience, not choice).

So advocates of patients might ask:

* Are the institution's methods for protecting your privacy adequate?

* Do they de-identify the sample and clinical data adequately (coding it) -- and who is the keeper of the key to that code?

* Do some institutions sell the clinically annotated samples to a commercial third party?
What are their policies about the use of it? Do these align with our beliefs?

So I'm not a fan of unspecified future use even if the risks are probably very small at this time. What are the indirect risks or adverse impacts? How often do our samples expire due to inadequate storage methods (rot on a shelf)? ... that could have been used to learn something of values if done somewhere else.

With standards and new analysis tools our tissue and blood are more likely to lead to insights about the disease. This information will increasingly guide therapeutic decisions ... including trial participation. Noting that our tumor samples cannot always be resected (safely) a second time in every patient.

So I'm inviting continued discussion on the need to reorient medical institutions - to focus use of our "gifts" of blood and tissue (and related consent) on disease-specific study and that consent should be on a per-study basis if used otherwise. For example, If the extra blood and tissue will be used for example to help train lab technicians ... then consent for that in the surgery consent document. (Using unidentifiable biospecimens for training … the boilerplate consent text should be fine).

The justification and need to involve patients more fully in consent has arrived .. and will only increase in the coming years. Medical centers doing biospecimen-based research might inform about the limits of that research (exploratory, laboratory only, etc) or adopt standards for captures, storage, analysis and protection of our associated clinical records (as keepers of our personal information and clinical records, and DNA). The institutions that take the lead may well attract more patients – helping to offset the financial costs.

In keeping with the oft-cited goals of personalized medicine as the root objective and justification for such research ... I am advocating (again) for making available a portion of appropriately stored extra tissue to guide participation in trials based on markers of risk and response that can be identified today with validated technologies. NCI MATCH seems an exciting example of the information in our tissue guiding promising research and giving hope to patients out of standard options: Good science and good medicine.


Karl Schwartz
Research Advocate, Lymphoma
 

Lessons Learned in CLL: the importance of cooperative biomarker-based research

Re: Dr Sharman's Blog 2014:
Ibrutinib in 17P deleted CLL http://bit.ly/UAnA7R 

Here we see an exemplary example of a biomarker that spares patients from ineffective therapy! If you have CLL with the 17p deletion (a specific mutation) then chemo will not work for you. Better yet, patients with this mutation respond great to a much less toxic targeted drug.

So as Dr. Sharman, notes - folks with 17p CLL do not have to try, suffer, and fail to benefit from chemo to use ibrutinib ... big news indeed!  How did researchers find this out?

According to an expert I consulted, the validation of the 17p biomarker took thousands of patients and cooperative research by investigators world-wide. It also helped that it's relatively easy to get tumor samples for CLL - from the blood.

Finally, the commercial sponsors took advantage of the cooperative group finding and demonstrated relatively easily that ibrutinib addresses an unmet need in this high risk group.

So what drives progress is good science - validated biomarkers that improve and guide (individualize) practice. Such progress REQUIRES patient participation in trials and cooperative research with biospecimens. There is NO other way. To make additional progress against lymphoma ... patients must also take part!
 

Giving Tissue and Blood - an advocate's perspective PDF 

* Slides PDF

Meeting the information needs of patients, and advocating for excellence in clinical science ... can work hand-in-hand.

Received positive feedback on this at Vail (Methods course in clinical research) ... most importantly from the faculty in the discussion group who recommended it be distributed widely.

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:

	To better monitor and improve patient safety (e.g., test for need to reduce dose when indicators drop suddenly)
	To proactively identify patients in trouble (e.g., are in danger of dropping out for safety / financial / social / physical / emotional reasons)
	To compare populations across studies in a another way (e.g., QOL scores were comparable) …  and
	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

Advocacy perspective on Phase I trials

Advocacy perspective: Ownership of Drugs Comes with Unique Responsibilities  

  
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 .

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.  

Patient Advocacy Background and Experiences: 

A link to my advocacy CV

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

Advocate Perspectives - old and new:

	On Ownership of an Investigational Drug  PAL
	On Pathways to Progress - 2014
	On Biomarkers - Draft: perspectives and resources  PAL
	On reasons for drug shortages, proposed solutions
	On Rising Healthcare Costs ... Threatening Access to Quality Cancer Care  PAL
	On Testing Upfront therapy for indolent lymphoma
	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
	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
	On recipe for progress
	On the basic elements for progress
	On the format of Reporting Abstracts Abstract-perspective.PDF
	On Finding & Evaluating Online Medical & Support Information  Slides: http://lymphomation.org/find-eval-final.PDF  Teleconference presentation for Nurses and Social workers: Sponsored by Lance Armstrong Foundation, Leukemia and Lymphoma Society, July 2009
	On Giving Tissue and Blood - an advocate's perspective PDF
	On Interest, attitudes, and participation in clinical trials among lymphoma patients with online access.    JCO  (fixed) Our study published: ASCO 2009:
	Letter to FDA on Transparency initiative PDF
	On Vaccines and Autism link: It's easy to confuse correlation with causation - Tony L. Hines
	On Accelerated Approvals
	Lymphomation Blog  (under maintenance)
	On Progression Free Survival: Does it predict better survival in Follicular Lymphoma? PDF
	On FDA transparency PDF
	On Radioimmunotherapy reimbursement policy  2009-CMS-letter.PDF
	On Drug Reviews, Vaccine misinformation, Level of Evidence PAL
	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: Detailed Statistics for NHL http://bit.ly/SEER-NHL Detailed Statistics for Hodgkins http://bit.ly/SEER-Hodkgins
	On Abigail Petition - Compassionate Use Proposal
	Letter to researcher: Dr. Rosenberg
	On AACR Molecular  Targets and Cancer Therapeutics 2005
	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:

	Guidance: Strategies for Finding and Evaluating Medical Information   As presented at Gilda's Club Delaware Valley, April 2006
	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? ...
	10 Rules for Redesign of Our Health Care System - IOM ~ Crossing the Quality Chasm

URGENCY & UNITY

	PAL's Mission
	Commentary on AACR Molecular  Targets and Cancer Therapeutics 2005
	Why we need the National Biospecimen Network
	Recipe for Progress Against Lymphoma
	OFF - Oneness, Fairness, Focus Rationale for a united effort
	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.

	Patient attitudes towards trials: Report from our Lymphoma Patient Survey regarding  interest and participation in clinical trials  PDF
	Perspective: Adaptive Design Conference, July 2006, Washington DC  Harmonizing Research Goals with Meeting the Clinical Needs of the Participants  (slides with narrative) PDF
	Perspective: Harmonizing Research Goals with Meeting the Clinical Needs  of the Participants - Apr 2006 - PDF  Presentation at Favrille Investigators Conference
	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.
	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
	"The patient is waiting" - patient perspectives on  aspects of toxicity and the need for innovation - PAL an appeal for NBN in a brochure format PDF
	Question:  Radiofrequency Ablation for lymphoma?  PAL
	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?
	Advocacy?  Radiofrequency Ablation for lymphoma? PAL
	What Makes A Study Desirable - Known Obstacles to Accrual -  Patient Perspectives on Clinical Trial Design 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
	WHEN? Expedite Gene Profiling - Routinely snap freeze lymphoid tissue at biopsy
	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.
	Perspective: The Need for Content and Structure Standards for Published abstracts
	Perspective: Changing the Treatment Paradigm for indolent NHL: treat early with novel agents?
	Perspective Patient Access to Emerging Therapies  for Incurable Cancers

Perspective: Bexxar Approval Petition Letter to the FDA  Update: The ODAC has since recommended the approval of Bexxar and FDA has approved it.

	Perspective:  What can we do to responsibly accelerate drug evaluations
	Perspective: Accelerated Approval for Low Toxic Therapies - Draft proposal to investigators & FDA
	Perspective: The Progress Review Group plan -  The PRG plan and why it needs to be carried out
	Perspective: Letter to Mark McClellan, MD, PhD Commissioner, Food and Drug Administration  Commentary on Abigail Petition - Compassionate Use Proposal
	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?

Resources for Research Advocates

Resources compiled

FUNDING AND INSURANCE COVERAGE

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

CT SCANS

	Question: Are patients with indolent cancers receiving too many CT scans?  Background information
	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