Clinical Questions with comments

[Guest guest]

Greetings,

One of our major goals is to help patients understand the critical role of

clinical trials in making PROGRESS AGAINST LYMPHOMAS / CLL and to provide also

general guidance on when we may reasonably consider clinical trials.

Please note that not all studies will have a control group and that a placebo

control (i.e., a sugar pill) is never used in oncology trials - the control will

be a standard of care.

=SOME CLINICAL QUESTIONS THAT CAN ONLY BE ANSWERED BY TRIALS:

A. Is this new drug effective when other agents are not?

Comment: Answering this question doesn't require a randomized study if the

refractory status of the patients is well documented. Easiest path to marketing

approval - accelerated / conditional approval.

B. Is protocol A better than protocol B for this type of lymphoma as first

therapy?

Comment: This question is vital to advancing the standard of care – making

evidence based treatment decisions. It can take a long time to accrue patients

and for data to mature. First treatment could be the best opportunity to cure

lymphomas or induce the most durable remissions which suggest a survival

benefit.

C. Is protocol A better than protocol B for this type of lymphoma at first

relapse?

Comment: Also vital to advancing the standard of care, improving survival and

helping to make evidence-based treatment decisions.

D. Is this protocol curative, and if so does the curative potential outweigh the

risks?

Comment: Takes a very long time for data to mature - up to 12 years for indolent

lymphomas. Historical controls may be sufficient, but studies need to be large

or replicated by independent groups. Patient selection bias is a problem in

single arm studies - such as picking younger patients with lower risk disease.

E. Does this protocol manage the condition better than observation? . does it

improve survival or quality of life?

Comment: With the emergence of many targeted therapies we have increased

potential to manage lymphoma by treating only as needed, or regularly with less

toxic doses when the protocol has less expected toxicity. Probably requires a

control group and random selection to objectively measure benefits and risks,

particularly if not all patients benefit, or benefits and adverse effects are

modest.

F. Does adding a new agent (concurrently or sequentially) to an effective

protocol improve outcomes without substantially increasing risks?

Example: the addition of Rituxan to CVP and CHOP. Related to other items above -

requires randomized studies and signficant follow up. A way to potentially

advance the standard of care by adding one agent and comparing with the standard

of care.

G. Can we remove an agent from a curative protocol to decrease toxicity without

compromising it's efficacy?

Comment: We see this question being asked in Hodgkins lymphoma, which has a very

high cure rate.

H. Can use of this agent or protocol to delay the need for cytotoxic therapy

without burning bridges?

Comment: We see this being studied for Rituxan as first therapy for indolent

lymphoma.

I. Who is the new or approved agent/ protocol for? Who will benefit from it, and

who will only suffer unproductive side effects (should do something else)?

Comment: Progress seem too slow on this front. Arguably, we do not need another

active drug nearly as much as how to predict who a drug is for. Who is doing

biomarker research? Does it require tissue? How can patients participate?

=BACKGROUND:

* How do you reliably measure benefits and risks?

Response rate?

Duration of response?

Toxicities and risks secondary to toxicity, such as risk of infection?

Impact on subsequent therapies?

Survival benefit?

An improvement in Survival is the most reliable endpoint or measure of clinical

benefit, because it accounts for known and unknown factors, but it is not a

practical measure for the indolent lymphomas because of the long survival and

opportunities we patients will have to try other treatments, which confound

assessment of any one.

* A drug or protocol is said to provide clinical benefit for a specific

condition when the treatment improves quality of life or survival, relative to

the natural course of the disease.

Because survival can be difficult to measure and compare in the indolent

lymphomas, progression free survival is a commonly used surrogate, thought to

reasonably predict survival benefit, but its significance depends on the

magnitude (months? Years?) and also possible offsetting toxicities.

By law, the sponsor must provide clear and convincing evidence that a new drug

provides clinical benefit. The evidence from clinical data requires independent

data monitoring and most commonly a controlled and blinded study administered in

multiple centers.

Another major goal of clinical trials is to help guide treatment decisions and

advance the standard of care, such as new uses of already approved treatments..

Treatment in regular clinical practice, case accounts, cannot inform or advance

clinical science in any meaningful way.

All the best,

~ Karl

Patients Against Lymphoma

Patients Helping Patients

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