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Patients Against Lymphoma


Support >  Laboratory Correlates in Clinical Trials:

When is it Ethical to Require Biospecimen Samples?

Last update: 07/10/2014

When is it Ethical to Require Biospecimens
from the Participants in Clinical Trials?

Further below: Laboratory Correlates - considerations for researchers:

Requiring that patients provide biospecimens (tumor tissue, blood, urine, and so on) for entry into a clinical trial is a contentious area … some stakeholders arguing that it can sometimes be a form of coercion … as in: sorry, no tissue, no trial. 

In a treatment study, the rationale for the need to acquire additional tissue (such as by biopsy) should be presented clearly, because it may not be a minor or risk-free procedure. Further, the need for a biopsy should be stated up front before the patient travels to the center and it should be a core part of the research study if required. 

Patients should look for eligibility criteria in the study protocol such as:

"Measurable disease by CT scan, defined as at least 2 lesions that measure >1.5 cm in a single dimension (one of which is superficial and easily accessible for biopsy)."

"The consent form should clearly indicate whether the new biopsy is required to make the treatment decision in the trial itself, or whether it is only done to provide information leading to future decision making (benefiting the future, but not the patient him/herself), a more altruistic decision to make."  (Hans, advisor to PAL)

Mike writes: 

"The rationale behind the requirement drives the ethics of whether a biopsy should be taken.

Does the biopsy help to safeguard the patient’s health?

It should be made clear to the patient that NOT giving consent for additional uses of the tissue -- beyond the trial -- will not exclude you from participating. 

Or, it may be necessary to examine it to confirm the diagnosis or the grade of the disease – both of which may be critical in accepting the patient for the trial.

(Similarly a bone marrow biopsy is required to make sure that you are eligible for radioimmunotherapy in regular clinical practice.)

In a clinical trial, researchers often need to know more than if you responded – the actual mechanism by which the experimental treatment is working [can be important to making additional progress against the disease].

Considering the woefully small participation in clinical trials overall, it is to researchers benefit to reduce the number of barriers erected to potential participants, and to collect only the tissue that is necessary to protect the patient and to validate the study results." 

There are many dedicated people involved in the approval of trial protocols, such as the Institution Review Board, the FDA and in many cases a team of experts, which will often include patient advocates involved in the vetting of the protocol. 

So in most cases when biospecimen is required it will be based on sound research principles, needs, and also attention to patient safety. 

For example, tissue might be required when there's a need to make sure that you are eligible for the trial protocol, or for studies of targeted drugs when it can be important to make sure that the drug that you will receive is appropriate  -- that the target exists in the tumor, in order to avoid giving you a drug that is unlikely to be effective but sure to have side effects. 

NOTE:  The existence of the target in the tumor cells improves only the plausibility that the drug can have an effect on the tumor, but it in no way assures that you will benefit - that you will live longer or better because of it.  

Can tissue from a prior biopsy be used instead?  It depends on what kind of information is needed from the tissue and how that tissue was captured, fixed, and stored; and perhaps how long ago it was acquired – because the lymphoma cells can change over time.  It may also depend on the willingness of the center that stores the tissue to release it to another center.

We cannot make progress against lymphoma (the purpose of research) without examination of the genetics and underlying biology of the cells, which can be unique to each patient, which needs to be correlated with clinical outcomes to help one day personalize our care.  

Most patients will appreciate the importance of this aspect of clinical research when it is explained well.   After all, who better than patients understand how important it is to avoid unproductive therapies that will only harm us?

Laboratory Correlates - considerations for researchers:

There are practical and ethical consideration in the design of a study that include laboratory correlates.  Here's our checklist:

Requiring biospecimen seems appropriate for these reasons:


To determine eligibility in the trial
(such as the diagnosis, validated biomarkers for safety or efficacy,
or if the target of the drug exists in the tumor).


To understand the safety of a new drug
(such as to determine how long it stays in the blood and where it accumulates).


To assess the efficacy of a new drug
(such as to determine if the drug is active in the bone marrow)


To prospectively validate biomarkers that appear to predict harm or benefit from the study intervention,
 when this is a primary or secondary objective of the study.

Questions that can help researchers to decide if providing biospecimen should be required or optional include:


What is the risk of the procedure, and how does the risk compare to the risks of competing protocols?


How much discomfort or fear (or perception of risk) is associated with the procedure,
and how likely is this to work against enrollment in your trial?


How important are the laboratory findings to helping to address an urgent unmet need
for the indication being studied? 


How strong is the biological rationale for the proposed correlative study?


How likely are the laboratory findings in your study to influence clinical practice
or to make important new discoveries?


How large is your study - is it sufficiently powered to do meaningful correlative research?


For a small study, can the laboratory correlates be pooled with the findings from other trials?


Are you using standardized assays and procedures that makes it feasible to pool
your findings with other studies?

Many thanks for the informed comments of advisors on this topic, which we've copied directly into the text.

~ Karl (advocate's perspectives)

Additional reading:

Issues Surrounding Biospecimen Collection and Use in Clinical Trials
Allison R. Baer, RN, BSN, Mary Lou Smith, JD, MBA, Deborah Collyar, BS, and Jeffrey Peppercorn, MD, MPH http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900874/
CFR - Code of Federal Regulations Title 21 - Basic Elements of Consent http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.25
bullet An advocate's perspective on Giving-blood-and-tissue.pdf
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For all medical concerns,  you should always consult your doctor. 
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