Is Real-World Evidence a Complement to Randomized Clinical Trials?

[hansjd]

Interesting article from Cancer Therapy Advisor (10 Jan 2019) on the complementary value of RWE (Real-world Evidence) to RCT (Randomised Clinical Trials) for those who believe in the value of both.

cancertherapyadvisor.com/ge...

[pjoshea13]

I pay attention to real world results (which never seem to be better than those of the clinical trial). Perhaps some of the patients would never have met the selection criteria? Perhaps the real world mix of patients was different? Perhaps there are more comorbidies in the real world. etc.

No doubt the purists disregard such studies

[NPfisherman]

I agree with pjoshea13 (Patrick). The real world evidence provides additional input and can provide additional options for those with an MO or RO who is open minded. The fact that metformin was shown to be beneficial for OS to metastatic prostate cancer patients with DM is now leading to the clinical trial to test this on non-diabetic patients. SABR-COMET, which was done using various cancers is leading to stereotactic radiation trials on oligometastatic prostate cancer patients. I was lucky to get stereotactic radiation based on an appeal using SABR-COMET by my RO.

Clearly, there is value to both, and when one is desperate to survive, then one will review all their options. People are bravely betting their lives on this forum. When I hear anecdotal stories, or review other literature here, then I read, weigh my options, and decide. Like them, I am a betting man.

Best of luck to all....

Fish

[Tall_Allen]

That article is fostering ignorance, which I am too often chagrined to see on this site and the internet. I see otherwise intelligent people hunt for observational studies that confirm their pre-existing biases. To put an observational study ahead of a randomized clinical trial (assuming they are both well done) defies every principle of scientific research since the beginning of the scientific revolution in the 16th century. When one has BOTH and they conflict, one throws out the observational study. When all one has is an observational study, it behooves us to understand the sources of bias. We err on the side of caution - if there is even one observational study indicating harm, we should walk away from that treatment. That's why Phase 2 clinical trials are used to rule something OUT but not to rule something IN. ALL observational studies notoriously suffer from SELECTION BIAS. Their purpose is to generate hypotheses for more rigorous testing.

The best way to get around the problem of how patients are treated in community practice is to include include such sites in a multi-institutional clinical trial. This is expensive. Lacking that, one can say that the results apply only to patients treated at top institutions. This is another reason that patients should seek out the best institution they have access to.

[tallguy2 in reply to Tall_Allen]

Well stated, thank you.

[PhilipSZacarias in reply to Tall_Allen]

I understand and mostly agree with your position, but I have a couple of points to make. The treatments offered by hospitals and clinics must be based on clinical trials as well as consensus in the therapeutic communities who then implement the protocols (e.g., ADT + docetaxel). When a patient, who has been recently diagnosed with metastatic PCa, reads the literature and multiple studies point to potentially useful adjuvants (diindolylmethane) or therapies (e.g., cytoreduction or RT of the prostate) which are not presently available, then the patient has to make a decision based on the best available information. The patient cannot wait for the clinical trails to be completed, because his disease is progressive and time is obviously limited. The patient has to gamble, hedge his bets. As for myself, I received SBRT to the prostate in 2017 which appears to be supported by trials and I have dropped adjuvants which upon a more in depth review show that a therapeutic dosage cannot be achieved (e.g., CBD). I expect to drop more as the reviews progress. I should mention that I carefully track my PSA and correlate changes in any part of the regimen (diet, exercise, drugs, adjuvants, etc.) that I follow with changes in PSA trend, which seems to work for me - I have managed to stabilize my PSA at 0.1 ng/l, but for how long I do not know. I believe in evidence based medicine, but sometimes we cannot wait. Regards, Phil

[Tall_Allen in reply to PhilipSZacarias]

I agree with you that decision-making under uncertainty comes with the territory. You may be interested in the following article. Bradford-Hill provided a checklist for evaluating studies that may not be within the highest level of evidence:

pcnrv.blogspot.com/2018/08/...

Let's take a closer look at one of the examples you raised: cytoreduction. Many database studies suggested their might be a benefit to treating the prostate in men with metastases:

onlinelibrary.wiley.com/doi...

ascopubs.org/doi/abs/10.120...

journals.plos.org/plosone/a...

europeanurology.com/article...

sciencedirect.com/science/a...

sciencedirect.com/science/a...

Looks like a preponderance of evidence all in one direction, right? However, when two randomized clinical trials (STAMPEDE and HORRAD) were done, there was NO benefit found, except when there were very few metastases.

pcnrv.blogspot.com/2018/09/...

What's going on? The problem is selection bias. In all the retrospective studies, the men who got the cytoreductive treatment were the ones who their doctors believed were most apt to benefit from it. Possibly because they had fewer metastases, possibly because their health status was better and they had fewer comorbidities, possibly their doctors had an intuition based on unmeasured variables. Even the best statistical correction techniques cannot compensate for systematic errors like that and missed variables. The best we can do when we don't have Level 1 evidence is look very closely at the strengths and limitations of each study (peer-reviewed articles always include such analyses).

[dentaltwin in reply to Tall_Allen]

Absolutely. I am very uncomfortable with the current push for right-to-try. It just seems too ripe with potential for exploiting the desperate.

[Tall_Allen in reply to dentaltwin]

There has only been one case so far:

raps.org/news-and-articles/...

[PhilipSZacarias in reply to Tall_Allen]

Thank you again for the helpful links. The first choice is always to review the results of clinical trials, which sometimes are not consistent with respect to results (then you to evaluate the studies for quality...not always easy when access to experts is limited). In the absence of clinical trials, then decisions are based on the best available information at a given time and not be taken lightly. One's position should change as new information from clinical trials becomes available. I will be the first to admit that I have to fight the tendency to "believe" instead of looking at only the facts. Cheers, Phil

[j-o-h-n]

Keep it Real, don’t take life so seriously, it isn’t permanent.

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 01/15/2019 5:02 PM EST