Clinical Trials >  Fostering the Informed and Routine
Consideration of Clinical Trials

Patients as active partners in clinical research

Last update: 08/30/2010

TOPICS
The terrible impact of low enrollment on clinical research  | 
7 Circumstances to Consider Trials | Questions for Your Doctor about Trials | Find Trials |
Projects | Proposals | Poverty of Riches | 
Related Articles

Topic Search:  ASCO | PubMed 

What Matters:  the completion of well-designed studies that provide meaningful answers, which informs clinical practice - making treatment safer and more effective.

Our goal is to foster the informed and routine consideration of clinical trials so that we can accelerate progress against lymphomas and CLL.

Update: Oncologist survey: 
Obstacles to enrolling patients in clinical trials 
 

ACT: Please Bring Survey to Your Next Consult   Raw data PDF Most commonly cited obstacles so far (n=51) Chart PDF Most significant obstacles Chart PDF

See also:

	Clinical Trials Search Tools
	Treatment Decision Schema: PDF

Action is needed There is an increasing number of investigational agents for lymphomas and a limited patient pool, approximately 5% of available patients.  Thus, increasing the rate participation in clinical research is as vital to progress as raising money for research - if not more so - particularly for lymphomas. Doctors and patients require enhanced tools to more readily locate studies appropriate to patient's clinical circumstances and treatment goals.   New policy is needed to make patient participation or consideration of trials more routine, particularly in these clinical circumstances We may need to provide financial incentives for community physicians to refer patients to appropriate clinical trials. Patient need to be aware of clinical trials and start the conversation about trials with their treating physicians and independent experts.  Doctor, for my diagnosis and clinical circumstance: What is the standard of care? And what clinical trials are appropriate? Investigators must provide the rationale for clinical trials protocols as a treatment decision, describing the potential to meet the clinical needs of the participants, which should be at least equivalent in potential to the standard of care. Investigators must provide real-world eligibility for trial enrollment, to improve enrollment and so that results predict outcomes in the real world. Investigators and the NCI must streamline the referral process / improve the resources (ClinicalTrials.gov) to locate studies based on clinical circumstances. We must provide patients with information about the standard of care and types of clinical studies, which can also be appropriate as therapy. We must advocate for insurance providers to pay for medical expenses related to study participation. We  must provide assistance for travel and lodging, a known obstacle to clinical trial participation.

YOUR ACTION IS needed! Distribute our clinical trials referral survey to your oncologist Open and print the survey PDF and bring to your next consult. Doctor, When time allows (and if you haven’t already done so), please complete and mail this very short survey? The patient community wants to help identify the reasons for low clinical trial enrollment, and also encourage the routine discussion of clinical trials that may be appropriate to our clinical circumstances. == If your doctor agrees, we ask that you apply the stamp at that time - to seal the deal, so to speak. See results  so far Chart

7 Reasons to Consider Clinical Trials: 
... based on your clinical circumstances

See also Questions that Can Be Only Answered by Clinical Trials PDF
 Feel free to print and distribute.

There are many clinical circumstances where a clinical trial can be at least as appropriate as standard care, and patients deserve to consider and have full access to such options. Achieving this goal can be vital for these individuals and is certainly required to make additional progress against lymphomas.

1. When standard therapies are not yet curative, and I desire or need to consider investigational protocols that have curative potential.

2. For an aggressive lymphoma when the relapse rate is high and I wish to improve my chance to cure the lymphoma, perhaps with consolidation* or maintenance* approaches.  
   
   * Consolidation meaning additional therapy shortly after the main treatment.  Maintenance meaning additional regularly scheduled therapy over a long period of time.

3. My need is for a therapy that has lower expected toxicities compared to standard treatments, which may not be appropriate for me because I'm elderly, have secondary conditions, or am in poor health.

4. I have indolent lymphoma and do not require therapy, but the need to treat soon is anticipated*

   *Anticipated? ... by increasing fatigue, or other symptoms ... or evidence of progression without symptoms (increasing nodes, decreasing counts).  
   
   If so, you might say ...

   Doctor: I’d like to consider investigational protocols of a type (targeted, immunotherapy) that have lower expected risk, which may regress or slow progression, which are also unlikely to "burn bridges" ... unlikely to preclude benefiting from standard therapies later on. 

   Note: Even excessive worry about progression could be sufficient reason to treat if the the worry is impairing your quality of life and you meet the criteria to treat.  See GELF guidelines on reasons to treat
    

5. I have disease that is resistant to standard protocols (refractory). I need to consider investigational protocols of agents with unique mechanisms of action - might be active when standard therapies were not.

6. I need to consider investigational protocols that are both novel (new mechanisms of action) and aggressive, which include allogeneic stem cell transplantation, due to having high-risk disease or bone marrow failure.

7. I have been offered two or three reasonable standard treatment, and have been informed that doctors do not yet know which protocol is superior (there is no standard of care).  
   
   ... I have no expectation about which protocol is best, so would like to participate in a controlled comparative study that can help discover which is best on average, or better still: which protocol is best for which patient based on biomarkers that predict response in future. (I wish to help advance the standard of care.)

How to get this vital conversation started?

Open and print the survey PDF and bring to your next consult.

In a nutshell:  no cure yet | high relapse rate for a aggressive lymphoma |
standard therapy is too toxic for me | sometimes while in watch and wait | 
I have refractory or high-risk disease | there's no standard of care

Questions to Ask Your Doctor or Nurse

Is there a study that's right for me (at this center or nearby)?

If so:

	What is the purpose of the study?
	How might I benefit from participating?
	What are the risks from participating?
	What were the results of other studies of this treatment?
	What other treatments could I receive if I don't take part in the study?
	How do the risks and potential benefits of the study compare with these?

If I join the study:

	How am I protected from possible adverse events?
	What tests are in the study, and how often are they given?
	Will I continue to see my current doctor?
	How will participating effect daily activities? Will I still be able to work or go to school?
	Will I have to be in the hospital?   How many days?
	What are the possible risks or side effects for me?
	Will my insurance cover procedures and tests?
	Will there be extra costs because of the study?
	How will I be checked after the study, and how often?
	How long will the study last and how long will I be tested?
	Will I be made aware of the results?

Evidence of Poor Enrollment Rates -
and the terrible impact on clinical progress

One in Five Cancer Clinical Trials Is Published:  A Terrible Symptom—What's the Diagnosis? http://theoncologist.alphamedpress.org/cgi/content/full/13/9/923   "half of the unpublished trials have failed to accrue and reach endpoints;  Nearly 60% of trials opened for 5 years had fewer than five patients enrolled at each site, and, for >20% of studies, not a single subject had been accrued. of all NCI phase I, II, and III trials opened and closed between 2000 and 2007,  only 50%–60% achieved minimal stated accrual goals.  So, while perhaps only one in five cancer clinical trials is ever published,  of those unpublished, a significant percentage probably died for lack of accrual.

Related Reports

	A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program http://bit.ly/a2rUEh "Clinical trials that test the safety and therapeutic benefit of promising treatments are essential in translating new knowledge into tangible benefits for patients with cancer. Four overarching goals should guide improvement efforts:   Improving the speed and efficiency of the design, launch, and conduct of clinical trials Making optimal use of scientific innovations Improving selection, prioritization, support, and completion of clinical trials Fostering expanded participation of both patients and physicians IOM Report: A National Cancer Clinical Trials System for the 21st Century Reinvigorating the NCI Cooperative Group Program  http://bit.ly/cOu3Xc
	Faltering Cancer Trials  nytimes.com  April 2010 The nation’s most important system for judging the clinical effectiveness of cancer treatments is approaching “a state of crisis.” That is the disturbing verdict of experts assembled by the National Academy of Sciences to review the performance of clinical trials sponsored by the National Cancer Institute.
	Progress and Deficiencies in Clinical Trial Reporting http://bit.ly/a9ffVv  "... the practice of publishing only some results, but not others,3,4 undermines our collective ability to make rational decisions about medical care.  ... Ethical clinical research should contribute to generalizable knowledge and improve human health. The dedication of patients who take the risks to participate in clinical research is dishonored when their data remain secret. "

Active and Completed Projects

To identify obstacles to participating in clinical trials, and find remedies: 

Interests, Attitudes, and Participation in Clinical Trials Among Lymphoma Patients With Online Access   Patient Survey on attitudes and participation in trials Web-based  (closed) Poster exhibit PDF  (accepted L&M Conference)   Narrative of Poster Exhibit  PDF   ASCO 2009  abstract | JCO

Discussion: Patient issues and perceptions regarding randomization, study risk, eligibility, and tests  and procedures suggest an opportunity to improve enrollment in clinical trials by focusing on these aspects of study design, specifically, attending to the rationale of the protocol as a treatment decision – having the potential to optimally meet the clinical needs and treatment goals of the participants, in addition to answering important clinical questions.
 

	To identify obstacles to the routine consideration of clinical trials:   Confidential CLINICAL TRIAL SURVEY For Oncologists Treating Lymphoma / CLL Patients PDF     ACTION: Patients: Please print the survey and bring to your next consult!   Raw data (preliminary n = 51)
	To make ClinicalTrials.gov searchable by clinical circumstances and goals:   Our proposal to NIH ClinicalTrials.gov group PDF This proposal has been received by NIH and forwarded to the PDQ group. A teleconference has been offered to discuss.
	To help patients and treating physicians to appreciate the vital role of clinical trials: Questions that Can Be Only Answered by Clinical Trials PDF

Related Perspectives

	Free brochure on this project for printing and distribution:   The Urgent Need to Increase Participation in Clinical Trials PDF
	Presentation on participation issues to industry and investigators:  Harmonizing Research Goals with Meeting the Clinical Needs  and Treatment Goals of the Participants PDF
	Questions that Can Be Only Answered by Clinical Trials PDF

A "poverty of riches"

There's an abundance of rationally designed promising new agents, which need to be tested as single agents, but also with existing protocols.  However, the pool of patients considering clinical trials remains very low, therefore studies failing to reach enrollment goals are increasing as the number of promising agents increase. 

It's as if you have a small pond with 100 fish, and a growing number of fisherman (once 10, now 20) testing new lures. Each contestant making it more difficult to know which if any is truly effective, useful, or best for which type of fish.

A marker for this was the prevalence of N=6, N=10, N=20 in presented clinical data. Such small populations, while customary in early phase studies, contributing to missed signals of benefit and risk. Low enrollment and delays in enrollment causing sponsors to reconsider if the investment is worth while - could ever lead to marketing approval. 

Conclusion: We urgently need to increase the pool of patients considering clinical trials by providing new tools and clinical practice policies.   For example:  (1) ClinicalTrials.gov must become searchable by clinical circumstance, so that physicians and patients can efficiently find studies that are reasonable to consider. (2)  Treating physicians must routinely consider clinical trials in various clinical circumstances, described above.

Overcoming obstacles to participation in clinical trials:

	Our proposal to Enhance ClinicalTrials.gov - make searchable by clinical circumstances  PDF
	Brochure: The Urgent Need to Increase Participation in Clinical Trials PDF
	Narrative from our survey on patient attitudes and interests Poster Exhibit  PDF
	Questions that Can Be Only Answered by Clinical Trials PDF
	Harmonize research objectives with meeting clinical needs and treatment goals    If patients fail to sign on in adequate numbers, the assessment of the therapy will not be made, no matter how well the study is designed from the point of view of regulators and drug sponsors.   Biospecimen-based studies are needed to address patient and disease heterogeneity.  Accounting for patient and disease variables could reduce risk (real and perceived) of study participation, making participation in a trial more attractive to patients than standard medicine.

Action: Encourage sponsors to consult informed patients, such as scientists with the disease, when designing clinical trials.

Action: Visualize the study protocol from the patient’s point of view – with an appreciation that patients have one life to experiment with.

	Does the protocol compare favorably to other options in this setting?
	Does it unnecessarily include tests that patients fear, such as bone marrow biopsies?
	Do the side effects preclude the use of treatments that may be needed later?
	Does the protocol include quality of life endpoints?
	Is there genuine uncertainty about which treatment arm in a randomized trial is best?
	Can you disclose outcome data as it develops, to foster trust?
	Are predictive tests used to identify who is likely to benefit, such as gene profiling? *

“Given the number of articles that describe the correlative and predictive usefulness of array-based molecular classifications, especially in leukemias, these outcomes no longer elicit surprise. But perhaps they should — not only because of their clinical usefulness, as outlined in the editorial by Grimwade and Haferlach (pages 1676–1678), but also because of the rapid pace at which expression genomics is changing the conduct of clinical research.”
 
NEJM ~ Vol. 350:1595-1597, April 15, 2004 No 16
 
Also see Patient perspectives on clinical trial design

Make it easier for doctors and patients to locate trials appropriate to the patients clinical setting and treatment goals ...  See Narrative of Poster exhibit for details:  PDF

Provide financial support for travel, lodging, and associated tests.   When patients participate in clinical trials they provide a service to society and deserve our support, perhaps even compensation.   These individuals are heroes. Action: Advocate for government assistance, especially for the uninsured, so that the financial limitations of individual patients do not impede progress or access to appropriate investigational therapies.   See Coverage of Health Care Costs for Clinical Trials - How does your state measure up?   Action: Educate patients about resources that can help patient to overcome these obstacles,  such as Travel for Treatment

 

Carry out the blueprint for the National Biospecimen Network  in order to conduct more efficient and humane drug development and evaluations: Standardized collection of biospecimens;  Find novel targets using microarrays; Refine diagnosis and identify high- and low-risk disease; Find clinically useful biomarkers by identifying correlations between gene expression profiles and responders;  Select the appropriate patients for targeted-phase studies. The result is that smaller studies will be needed to achieve statistically significant results, providing relief from the competition for patients.  Fewer patients will be subjected to the toxicity of drugs that cannot help them.  The new favorable circumstances – replacing trial and error – will cause increased interest in trials and cancer research among patients, investigators, and commercial entities... See background on National Biospecimen Network

Encourage “trial talk” between the patients and treating physicians  Action: Help patients and physicians to locate appropriate studies by:    using the lymphoma-specific queries of ClinicalTrials.gov on our website;  advocating for patient-friendly descriptions of clinical trial protocols and links to related data;  encouraging sponsors to list studies in ClinicalTrials.gov as mandated by FDA.  NOTE: We consult with patients and experts to identify notable clinical trials for lymphoma,  and invite drug sponsors to inquire about adding protocols to our list.    See Clinical Trials of Interest for Lymphoma.   Action: Provide community physicians with incentives for referring patients to clinical trials.  Action: Involve community physicians in the administration of clinical trial protocols. Action: Educate patients about the true risks of the disease, the potential of investigational treatments, and the limitations of standard therapies.  See, for example  About Lymphoma Action: Encourage patients to consult lymphoma experts to get objective opinions about investigational therapies. See Doctors page.  Action: Advise patients to have the experts they consult contact their treating physicians in order to reach a consensus on what treatment protocol is best for them. Action: Help patients to review consent forms, contact investigators, and complete applications.  Action: Inform patients on how to better evaluate medical claims and data.

Create innovative trial designs with the potential to make a positive difference in patients' lives  The time to get creative is early in the course of the disease, when the patient has better immune competence, less tumor burden, and has had fewer exposures to toxic therapies.  Action: Develop front-line protocols, combining aggressive approaches in combination and/or in sequences with biological and immune-based therapies, that provide the potential for curing or extending survival in difficult to treat lymphomas.  Action: Develop front-line protocols for indolent lymphomas that combine or sequence low toxic target biotherapies and immune-based therapies with the goal of managing the disease with minimal toxicity.    NOTE: Without publicity, a frontline idiotype vaccine study completed accrual in two weeks.   Action: Develop protocols that induce active immunity against tumor antigens, and that may overcome ways that tumors escape or suppress immunity.  Action: Reduce reliance on quick response agents when the responses are not durable and the side effects, such as myelosuppression, contribute to complications and limit future options. Action: Develop protocols for refractory end-stage disease that can extend survival while improving quality of life.

Related Resources & News

Topic Search: Clinical Equipoise (genuine uncertainty in randomized studies)

	The Urgent Need to Increase Participation in Clinical Trials PDF
	Cancer Trial Participants Rarely Told of Results Medscape (free login req.) "That may be changing, however, as patient advocates and some clinical researchers assert that offering results recognizes patients as partners in the research process, according to Dr. Partridge."
	Clinical Trials of Interest for Lymphoma
	Coverage of Health Care Costs for Clinical Trials - How does your state measure up?
	Consult with outside experts
	Evaluating Medical Claims and Data
	Finding lymphoma clinical trials, made easier
	National Biospecimen Network
	Patient perspectives on clinical trial design
	Review the article: Experimental Therapy, End-of-Life Care Can Coexist Tue May 21, 7:12 PM ET HealthScoutNews
	Travel for Treatment Lymphomation.org
	Obstacles to the accrual of patients to clinical trials in the community setting. Winn RJ. Semin Oncol. 1994 Aug;21(4 Suppl 7):112-7.
	Understanding the attitudes of the elderly towards enrolment into cancer clinical trials  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1382233/?tool=pmcentrez   "The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials.  ... Cancer is a disease of the elderly with 60 % of cancers occurring in those over the age of 65 years [1]. As our population ages it will become increasingly critical to optimise treatment in older patients to ensure both good quality of life for this group and the best allocation of medical resources."
	Barriers in phase I cancer clinical trials referrals and enrollment: five-year experience at the Princess Margaret Hospital  ncbi.nlm.nih.gov