TOPICS
The terrible impact of low enrollment on clinical
research
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When to Consider Trials? |
Projects | Proposals
| Poverty of Riches |
Related Articles | ACT: Please
Bring Survey to Your Next Consult PDF
Topic
Search: ASCO
| PubMed
 Our
goal is to make the consideration of clinical trials
more
routine
so
we might accelerate progress
against lymphomas and CLL.
Encouraging
patients and treating physicians to
become active partners in research!
Update:
Oncologist survey:
Obstacles to enrolling patients in
clinical trials
Additional progress is urgently
needed
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There is an increasing number of investigational agents for lymphomas
and a limited patient pool, approximately 5% of available patients.
.. Thus, our participation in clinical research
is as
vital to progress as raising money for research.
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Doctors and patients require enhanced
tools to more readily locate studies appropriate to patient's clinical circumstances and treatment goals.
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New policy is needed
to make patient participation or consideration of trials
more routine, particularly in
these clinical circumstances
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Provide
financial incentives for community physicians to refer patients
to appropriate clinical trials. |
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Patient
to be aware of trials and to discuss trials with their
treating physicians and independent experts.
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Provide
the rationale for clinical trials protocols as a treatment
decision, describing the potential to meet the clinical needs or treatment goals
of the participants. |
| Provide
real-world
eligibility for trial enrollment. |
| Streamline
the referral process / provide resources for treating physicians. |
| Educate
patients about study types and provide assistance for travel and
lodging |
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YOUR ACTION needed!
Distribute
Clinical
Trials Referral Survey to your Oncologist
Open and print the survey PDF and
bring to your next consult.
See results
so far Chart |
When to Consider Clinical Trials:
based on clinical circumstances
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
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When standard therapies are not yet
curative, and I want or urgently need to consider protocols that
have curative potential.
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| 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.
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My need is for a therapy that has lower
expected toxicities than standard treatments, which may not be
appropriate for me because I'm elderly, have secondary conditions,
or am in poor health.
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I have indolent lymphoma and do not require
therapy, but the need to treat soon is anticipated.
... 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:" preclude benefiting from standard therapies later on.
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I have disease that is resistant to
standard protocols (refractory). I urgently need to consider
study protocols of agents with unique mechanisms of action - might
be active when standard therapies were not.
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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.
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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.)
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Evidence of Poor Enrollment
Rates - and impact on clinical progress
|
 | "half of the unpublished
trials have failed to accrue and reach
endpoints;
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| 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.
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| of all NCI phase I, II, and III
trials opened and closed between 2000 and
2007,
only 50%–60% achieved minimal stated accrual
goals.
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| 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.
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Active and Completed Projects
To identify
obstacles to participating in clinical trials, and find remedies:
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Interests, Attitudes, and Participation in Clinical Trials Among
Lymphoma Patients With Online Access
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Patient
Survey on attitudes and participation in trials Web-based (closed)
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Poster
exhibit PDF (accepted L&M
Conference)
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Narrative
of Poster Exhibit PDF
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ASCO 2009
abstract |
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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.
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To identify obstacles to the
routine consideration of clinical trials:
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Confidential CLINICAL TRIAL SURVEY
For Oncologists Treating Lymphoma / CLL Patients PDF
ACTION: Patients: Please print the survey and bring to your next consult!
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Raw
data (preliminary n = 51)
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| To
make ClinicalTrials.gov searchable by clinical circumstances and
goals:
| Our
proposal to NIH ClinicalTrials.gov group PDF
Update:
This proposal has been received by NIH and forwarded to the
PDQ group.
A teleconference has been offered to discuss.
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Related Perspectives
| Free brochure on this project for printing and
distribution:
New The Urgent
Need to Increase Participation in Clinical Trials PDF
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Presentation on participation
issues to industry and
investigators:
Harmonizing Research
Goals with Meeting the Clinical Needs
and Treatment Goals of the Participants PDF
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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
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| Brochure: The Urgent
Need to Increase Participation in Clinical Trials PDF
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| Narrative from our survey on patient
attitudes and interests Poster Exhibit PDF
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| 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.
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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.
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Does the protocol compare favorably to other options in this setting? |
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Does it unnecessarily include tests that patients fear, such as bone marrow biopsies? |
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Do the side effects preclude the use of treatments that may be needed later? |
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Does the protocol include quality of life endpoints? |
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Is there genuine uncertainty about which treatment arm
in a randomized trial is best? |
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Can you disclose outcome data as it develops, to foster trust? |
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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
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Carry out the blueprint for the National Biospecimen Network
in order to conduct more efficient and humane drug development and evaluations:
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Standardized collection of
biospecimens; |
| Find novel targets using
microarrays; |
| Refine diagnosis and identify high- and low-risk
disease; |
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Find clinically useful biomarkers by identifying correlations between gene expression profiles and
responders; |
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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
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Encourage “trial talk” between the patients and treating
physicians
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Action:
Help patients and physicians to locate appropriate studies
by:
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using the lymphoma-specific queries of ClinicalTrials.gov on our
website; |
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advocating for
patient-friendly descriptions of clinical trial protocols
and links to related data; |
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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.
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Action: Provide community physicians with incentives for referring patients to clinical trials. |
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Action: Involve community physicians in the administration of clinical trial protocols. |
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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 |
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Action: Encourage patients to consult lymphoma experts to get objective opinions
about investigational therapies. See Doctors
page.
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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. |
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Action: Help patients to
review consent forms, contact investigators, and complete applications. |
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Action: Inform patients on how to better evaluate medical claims and data.
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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.
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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. |
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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.
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Action: Develop protocols that induce active immunity against tumor antigens, and that may overcome ways that tumors escape or suppress immunity. |
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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. |
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Action: Develop protocols for refractory end-stage disease that can extend survival while improving quality of life.
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Related Resources & News
| The Urgent Need to Increase Participation
in Clinical Trials PDF
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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."
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| Review the article: Experimental Therapy, End-of-Life Care Can Coexist
Tue May 21, 7:12 PM ET HealthScoutNews
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| 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."
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| Barriers in phase I cancer clinical
trials referrals and enrollment: five-year experience at the
Princess Margaret Hospital ncbi.nlm.nih.gov
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Topic
Search: Clinical Equipoise (genuine uncertainty in randomized
studies)