open access: Why Do Phase III Clinical Trials in Oncology Fail so Often?

Why Do Phase III Clinical Trials in Oncology Fail so Often?

 "Achieving success in the development of a cancer drug continues to be challenging. Given the increasing costs (1) and the small number of drugs that gain regulatory approval (2), it is crucial to understand these failures. In this issue of the Journal, Gan et al. (3) reviewed 235 recently published phase III randomized clinical trials (RCTs). They report that 62% of the trials did not achieve results with statistical significance. Trying to explain the high failure rate, they note the actual magnitude of benefit achieved in a clinical trial (designated B) is nearly always less than what was predicted at the time the trial was designed (designated δ) and conclude, “investigators consistently make overly-optimistic assumptions regarding treatment benefits when designing RCTs.”

But really should we be surprised that phase III trials, the venue for detecting “small” differences, so often disappoint? Almost by definition, phase III studies are designed to detect small differences (4,5). The problem is that small has given way to “marginal” as outcomes have fallen below our already modest expectations. And who or what is to blame? Are investigators really overly optimistic regarding experimental therapies and, as the authors suggest, responsible for the large number of negative studies? Although we agree that optimism regarding clinical benefit may lead to an underpowered trial, we disagree that optimistic investigators are those we should blame. We would ask, how do Gan et al. (3) define optimism? Where do they place the line between an optimistic and a realistic expectation?.........

Hope with More: In Their Own (Ovarian Cancer) Words

reposted from September 11th: 

Hope with More: ‘In Their Own (Ovarian Cancer) Words’©

September 11th, 2009
Author: Sandi Pniauskas


Still today, less than 20% of ovarian cancers are diagnosed in early stages, primarily one of luck or happenstance. Ever-present are the realities that ovarian cancer is a disease most often en-shrined in significant suffering. This is our past and this is our current reality.

Reflecting on our women’s most intimate and unpublished thoughts, feelings and opinions tells, ‘In Their Own (Ovarian Cancer) Words’, what still has not and is not being heard. This is not the ‘cute’ side of ovarian cancer, although there are moments. Each day brings a kaleidoscope of emotions. With each passing day, the struggles of the fine line between Hope, Reality, Wishes, Expectations and Dreams remain.

We speak as one without boundaries and indeed in many respects ovarian cancer IS the silent killer. Against our will and with significant sacrifices, this ovarian cancer invariably defeats the body and the spirit. I challenge you to listen, as we have, so silently, for so long. A decade of intimate involvement with ovarian cancer women, their caregivers and communities, has most often elicited truisms that stand out. There is Trust between Survivors & Caregivers and secondly, there does not exist, in our world, an ‘ordinary’ ovarian cancer woman.

Trust between ovarian cancer Women and Caregivers is: Hope with More.

Should we choose we might learn much based on these personal conversations. These few words represent a microscopic-sampling of millions of words and thoughts - all valued - all cherished – sometimes dismissed. Sometimes too difficult to b/hear. Sometimes with a huge sigh of relief and humour.

In our communities, many moments are spent living-with-ovarian cancer, often through the eyes of others. As a tribute to our ovarian cancer women, living-with or in-spirit, these are their words to you with that special privilege of Trust and my own personal admiration… in their own words. Some are stunning. All are real.

Age:
A: Ovarian cancer for xx-something ‘dummies’.
L: Older than whom?
I: How dare they write me off.
S: I have wished it was me, not her going thru this . Though I am younger and could be stronger, the truth is I am such a coward compared to her.

Angels & Hope & Friends:
B: I am alive today because of my guardian angel {an ovarian cancer survivor).
B: Spent all day in emergency because I was having a lot of trouble breathing. Good news no heart
attack, no stroke.
R: Please visit me today as I think this is it…. Please visit me today as I think this is it….(X many) … Look after yourself and when you have time, contact me at: 1 – 800 – HEAVEN ext R … Message to R: The line has been kind of busy ....
Y: Friendship therapy is something that has not been explored by the medical community, but it is important for cancer survivors. When I was on chemotherapy, I might just sleep over some days because during those days I was too sick to eat or get up. I was surprised I was enjoying not only the good companies, but also the food when other survivors came to visit me.
L: …will be shutting down the computer now...we’ll see each other completely on the other side.
C: I agree, let’s go, we can. (do this)
C: I think I will lean heavily on philosophy as I get closer to dying. It's that or religion. There's always food! Maybe I'll just eat my way through the fear of death!
S: I have to say that I am not being very gracious here and at the same time not feeling that I should
apologize either. It makes me feel that I am supposed to be wishing you the best when all I really am
wishing for is that you could stay.

CA125:
S: I was 3x years old when I was diagnosed…. I have never had a CA 125 done to my knowledge.
S: It doesn’t matter what the research on the CA125 says - it’s all we have.

Humor:
J: (Dr.) said if his wife was going for (treatment) this is who he would send her to. I hope he likes his wife!!!!
S: I should have read the bio first - psychiatry and 'suck it up' don't really go together.
S: Thanks for living so long! (woman with 150~ + chemo/multiple surgeries TO woman with no recurrence)
L: This disease may have taken my ovaries but has replaced them with a ‘set of balls’.


Husbands/Partners:
D: I watched, as the verdict was read, a tsunami-like wave pass right over my wife’s head, leaving her completely stunned.

Knowledge:
A: Ovarian cancer for xx-something ‘dummies’. (worth repeating)
S: In order to be taken seriously, we (patients) need to understand everything about ovarian cancer.
C: I decided that starvation is the easier death by far….
B: I once read that ovarian is the most complicated cancer, so I figure that I (and the rest of us) must be really special.

Impact:
B: “You need a surgeon and you need one now”. I left his office naively thinking that something would be done and that we could go back to trying to have children.
L: (upon my death) please thank everyone in our group...they are so special.
R: (favourite quote) "Since my house burned down I now have a better view of the rising moon."
F: I always wonder which (ovarian cancer friend’s) death will put me over the edge. I think I am close.

Value and Sense of Worthiness:
K: I feel I am nothing for what this disease is doing to my family (control)….I am not a nothing...I am really a somebody...somebody with ovarian cancer.
L: Let me tell you what is on my mind without cutting me off with "You are so negative!” It is not that I am being negative, these are the facts and I am being realistic.
D: (word games) I Am No Thing. I Am. Not a Thing, or a title, nor am I a summary of accomplishments. I am No Thing because I am not static, not uniform, not in a box, not a disease, not a political party. I am not a snapshot.
C: (published) “Devaluing a Survivor’s Challenge”

We are: PhD’s, healthcare support professionals, lawyers, bankers, physicians, teachers, social workers, computer specialists, nurses, realtors, bankers, e-patients...…Daughters, Sisters, Mothers, Grandmothers

*As matters of integrity, names have not been disclosed, albeit many have given their express permission to do so (past and present)