case reports dismissed with a single word: anecdotal. But why?

[Guest guest]

Greetings,

As laypersons we might expect that evidence of benefit from an intervention

is not difficult to come by - that an individual outcome is proof enough:

did this and is still without evidence of lymphoma. PERIOD.

Such accounts are dismissed by scientists with a single word: anecdotal.

But why?

I think the explanation requires some background starting with an

appreciation of the variable natural history lymphoma (treated and

untreated) -- even within the same subtypes (follicular, MALT, DLBCL, etc).

For example, ALL of the following approaches have led to

Much-Better-Than-Expected Outcome in some cases of indolent lymphoma:

Observation alone (spontaneous remissions),

Rituxan mono-therapy,

Fludarabine or F with other drugs

Chlorambucil only, or with Rituxan

CHOP-R, CVP alone, CVP with Rituxan,

Bexxar, Zevalin (RIT)

And some of these cases look like cures - with no evidence of disease 7, 10

or more years -even before Rituxan.

Standard drug therapies for lymphoma are sometimes called " backbone "

protocols - interventions that proven to be better than no treatment when

treatment is needed, . on which we want to build on and improve.

The fundamental problem with any case report (aside from a determination of

its accuracy) being we can't clone ourselves and therefore we can't be sure

that we would have done worse with some other approach.

Further, the more variable the natural history of the medical condition, the

less " faith " we can have in individual results - and the indolent lymphomas

are notoriously unpredictable - ranging from near-benign in its clinical

behavior, to very manageable, to rapidly fatal - thankfully, the latter

clinical course is a minority.

Because there are cases where all of the backbone protocol alone has led to

results suggesting a cure, we can't be sure if having added vaccines, or

RIT, Rituxan maintenance, or . led to a better-than-expected outcome in any

individual case.

Did have a lymphoma with an uncommon biology, highly sensitive to the

chosen backbone therapy? ... Was the outcome influenced by some other

unknown factor? Most importantly - and getting at the bottom-line purpose

of clinical research: Do the results of a case, or even a single-arm study

with an investigator-selected population, predict outcomes in others?

This is not to suggest that anecdotal reports cannot help to inform what to

study. But only to explain that in most cases only the evidence from a

Randomized Controlled Trial can be considered " practice changing, " - leading

to genuine progress - to better and safer therapies -- providing a

reliable new backbone on which to build.

Finally to an article that describes RCTs:

=Fundamentals of Clinical Research - Randomized Controlled Trials

http://bit.ly/f384qx

Snips:

" the act of randomizing patients to receive or not receive the intervention

ensures that, on average, all other possible causes are equal between the

two groups. Thus, any significant differences between groups in the outcome

event can be attributed to the intervention and not to some other

unidentified factor. "

" The size of the expected effect of the intervention is the main determinant

of the sample size necessary to conduct a successful randomized controlled

trial. Obtaining statistically significant differences between two samples

is easy if large differences are expected. However, the smaller the expected

effect of the intervention, the larger the sample size needed to be able to

conclude, with enough power, that the differences are unlikely to be due to

chance. "