Be careful about the studies you see ... - Advanced Prostate...

Advanced Prostate Cancer

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Be careful about the studies you see posted on this site

Tall_Allen profile image
91 Replies

The wonderful thing about this site is we are free to post anything we want within the bounds of civility. But that is also a danger - many people post studies without regard to truth. Truth is judged by the scientific process.

Two studies this week illustrate why patients should never use retrospective observational studies on drugs to make treatment decisions: metformin and cholera vaccine.

Metformin

I won't say yet that metformin has been conclusively proven to have no effect in prostate cancer (we await definitive results of the STAMPEDE trial). But I will say that all the upper level evidence is so far against it. And there is a proven increase in serious side effects from using it. Again, here's our best quality evidence so far:

prostatecancer.news/2019/11...

Cholera Vaccine

As for cholera vaccine, here is what was posted by George71, Nalakrats, LearnAll, etc. on this site 3 years ago:

healthunlocked.com/advanced....

healthunlocked.com/advanced...

healthunlocked.com/advanced...

Here was my response at the time:

"Association is NOT causation. There were 89,142 men in the Swedish registry, but only 841 (1%) men who received the vaccine to prevent cholera. The first suspicion is "selection bias" - in what ways were the men who got the vaccine DIFFERENT from most men? I suspect there were more health care workers who are more attentive to catching diseases (including prostate cancer) early, more educated, and may have gotten a wide range of other therapies (e.g., chloroquine, an anti-malarial, has some effect on PC cells in lab studies). These suspicions are borne out in Table 2. Cholera vaccine users were:

- Younger

- Diagnosed earlier

- More educated

- Higher income

- Diagnosed at an earlier stage

- Less likely to have comorbidities (diabetes, heart disease, COPD, hypertension)

Even with statistical adjustment (which assumes significant overlap), the biases are way too large and unmeasured confounding variables (like PSA testing, chloroquine use, lifestyle, diet, smoking, health care workers) too important to draw any useful conclusions."

Today the Swedish researchers wrote:

"Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding."

sciencedirect.com/science/a...

This is not to toot my own horn, but I spent 20 years on the job studying research methods and statistics. It is not easy. Why one study is only useful for hypothesis generation and another constitutes proof is not at all obvious. And cancer patients are desperate for anything that will help. This is just to say, be careful and check everything you put into your body with your oncologist.

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Tall_Allen
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91 Replies
BobbyMac07 profile image
BobbyMac07

Thank you for educating us!

rayben profile image
rayben

Thank you for all your posts.

Spyder54 profile image
Spyder54

I also felt your vibe on the Intermittent ADT, as no one seems to have the same protocol. I too await the Stampede Trial on Metformin, and 5 year results on Arm H of Stampede. I thought the 81% OS at 3 years was better than most Arms. You see, many of us are listening to you Allen

ocman profile image
ocman

Allen, thanks for taking the time to help clarify things, it's greatly appreciated!

monte1111 profile image
monte1111

I am also a very close listener. And I give you my heart felt thanks for what you do. If my oncologist knew everything I put into my body, she would fall down onto the floor and start flopping.

j-o-h-n profile image
j-o-h-n in reply to monte1111

I think you meant if you take off your mask.....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/26/2022 6:27 PM DST

Boywonder56 profile image
Boywonder56 in reply to j-o-h-n

Looks like you did j.o.h.n.......

j-o-h-n profile image
j-o-h-n in reply to Boywonder56

Most people tell me to put it back on (what a mean group).....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/26/2022 8:05 PM DST

monte1111 profile image
monte1111 in reply to j-o-h-n

Is that you j-o-h-n? I never knew I liked gourds so much. I haven't seen my doctor in at least a year, even by Zoom, I don't think she would even recognize me. The mortality rate goes down every time doctors go on strike. More people go to heaven when pastors go on strike. Etc, etc. Let's just hope that Tall_Allen doesn't go on strike.

j-o-h-n profile image
j-o-h-n in reply to monte1111

Thanks for the hint......(back to the gourd)...Tall Allen on strike? No way.. with all that money he makes selling his books with a free package of weed?

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/26/2022 8:10 PM DST

Fiddler2004 profile image
Fiddler2004

We hope and pray each day that science may someday find its way to a cure for our disease be it through mRNA, Off-Label drugs, genomics, artificial intelligence, an as yet unknown substance in the rain forests , who knows? Still we hope and pray each day.

We read, research, dig deep, keep journals, looking for something others may have missed, ah but alas, the variables are too great, our minds stay nimble as our bodies weep, still the hope and faith we keep.

Day after day, month after month, year after year, until we realize we are the lucky ones, grateful to still be here sharing each day with each other, family, friends, and loved ones.

Thankful for you Tall Allen, and others like you here on this forum, that have been willing to share your research and experiences with us, helping to make our journey’s all the more hopeful and fulfilling.

The hope and faith we keep.

Someday!

KocoPr profile image
KocoPr

Thanks Allen , im still learning and won’t stop.

CWT53 profile image
CWT53

Thank you Tall Allen for sharing your expertise.

CAMPSOUPS profile image
CAMPSOUPS

As always my big thanks to you TA for your dedication to us.I'm thankful too that the medical care I receive from my Dr.'s is also based on science based evidence. I can't imagine being diagnosed with full blown PC and the Dr. suggesting I travel to Canada and get a Cholera vaccination.

The internet hasn't helped in terms of feeding desperation for a hope for more than what is proven.

With my dx and volume of disease it has become frustrating at times to come here to the forum looking for real treatment information and trials only to find the posts and threads clogging the forum with confounding studies and irrelevant approaches that are shots in the dark.

I can imagine some thinking they are helping by "uncovering studies and sharing" and feel they are helping. I find these study posts to be placebo's for prevention,the active surveillance men, or the men with a chance for cure wanting to do everything possible to insure it. And again I say placebo's not treatment.

In my life before full blown PC some of these studies would have possibly been entertaining reads and something to ponder but now frustrating here where now I am not looking for an entertaining science study. Things are serious now. Time is not on my side. I need proven treatment.

Tall_Allen profile image
Tall_Allen in reply to CAMPSOUPS

I am reading a wonderful book now that moved me to post this thread. It is by Jonathan Rauch " the Constitution of Knowledge: a Defense of Truth ." Although he is mostly concerned with "fake news," much of what he says is applicable to science as well.

He says that the constitution of knowledge is constructed with peer review and replication, specialization, governing institutions (scientific societies and professional bodies), and voting (citations and confirmations). This is constituted in medical science by peer-reviewed publication, replicated prospective clinical experiments, agreed upon levels of evidence, altimetric attention scores, professional citations and GRADE bestowed by professional societies.

While anyone can express a hypothesis, patients should insist on facts before making treatment decisions.

CAMPSOUPS profile image
CAMPSOUPS in reply to Tall_Allen

The erosion of the constitution of knowledge certainly fits what has occurred with both "news" and science in the present day.

Schwah profile image
Schwah

Interestingly this study found the same huge impact from cholera vaccine as the study it supposedly debunks. As I read it, the only evidence that the cholera vaccine didn’t actually reduce deaths was that other vaccines also reduced deaths. To me, this could also mean that certain vaccines somehow rev up the immune system to fight cancer.

Schwah

Tall_Allen profile image
Tall_Allen in reply to Schwah

We know that observational studies are plagued by selection bias. To the study's authors, that explanation fully explains the association observed. They blame their observation on "healthy traveler bias" as I proposed 3 years ago. One doesn't have to jump through hoops to find a reason.

Your conclusion is not supported by the evidence. One of the characteristics of the kind of pseudoscience you are espousing here is that no evidence is good enough:

prostatecancer.news/2021/07...

I'm sorry you were hoodwinked. You are not alone. It's time to move on.

Schwah profile image
Schwah in reply to Tall_Allen

I say with the upmost respect as I know your knowledge in this area far exceeds mine. I was not hoodwinked as I did not state any conclusion. What I said was, “To me, this could also mean that certain vaccines somehow rev up the immune system to fight cancer.”

Isn’t that hypotheses also a possibility? And as you always say (and I agree) isn’t the only way to know which hypothesis is correct is a double blind phase 3 study?

Schwah

Tall_Allen profile image
Tall_Allen in reply to Schwah

I meant you were hoodwinked into pursuing cholera vaccine 3 years ago:

healthunlocked.com/advanced...

There is a principle called "Occam's Razor" in science. It means that the simplest (most parsimonious) explanation is usually the right one. Your hypothesis that all vaccines are protective is possible, but unlikely. As you, of all people, are well aware, prostate cancer is immunogenically "cold." It is therefore, highly unlikely that people taking any number of vaccines are protected against prostate cancer too. You would have to explain why we, the most vaccinated generation in history, still got prostate cancer at the rate of 1 in 7. This is what I mean by "jump through hoops".

A very simple explanation, common to all observational studies, is selection bias.

Schwah profile image
Schwah in reply to Tall_Allen

Yea, gotta admit that’s a pretty good argument. At least I didn’t get cholera.

Schwah.

monte1111 profile image
monte1111 in reply to Schwah

I probably have cholera and don't even know it. Guess this means throw your Gillette away and grow a beard. There is an ongoing study of the hazards of wearing baseball caps.

Boywonder56 profile image
Boywonder56 in reply to Tall_Allen

Thats why i leave the hard thinking to you ta....i tried to read research on ductal hystology......and after reading so much my brain hurt...i knew about as much as i did when i started....its rare ....so rare in fact littlle is known at the time....but they sure spun alot of hard to pronounce words...et al.....to form the hypothessis......its a rare cribiform......but my guess the grant money .......is justified in the translation...thanks for keeping us centered....bw

LapisLazul41 profile image
LapisLazul41 in reply to Tall_Allen

The possibility that many vaccines given post diagnosis may be protective is not unlikely; possibly explained by the hypothesis that it generically revs up the immune system; as Schwah offered. ------- You say that prostate cancer is immunogenically "cold"; but curiously it is the only cancer that has a proven post diagnosis "therapeutic" vaccine: Provenge. Provenge is testament, at least for some patients, that the adaptive immune system is activated in a seemingly "cold" cancer. ------- As far as generic activation of the innate immune system, look no further than IL-2 and interferon for melanoma and before that BCG for bladder cancer. The effectiveness of these non-specific activations were key historic developments in making "immunotherapy" the emerging 4th pillar of cancer treatment. On another note just in the news, from an observational study, and thus, as you so correctly emphasized, just hypothesis generating, is the following:

" Flu vaccine could reduce the risk of Covid morbidity"

doi.org/10.1101/2022.05.09....

Mihai Netea, an infectious-disease specialist at Radboud University Medical Center in Nijmegen, the Netherlands states: The observation that influenza vaccines are linked to a reduction in not just SARS-CoV-2 infections, but also disease severity, strongly suggests that the protection is genuine.

Admittedly, this hot off the press release, May 10, 2022, is a pre-print and not peer reviewed yet.

Tall_Allen profile image
Tall_Allen in reply to LapisLazul41

Sadly, Provenge is the only immunotherapy that has ever been approved for prostate cancer. It is not just a vaccine - it takes autologous dendritic cells and enhances them outside of the body. For many reasons, which you can look up, prostate cancer is immunologically cold- the same immunotherapies that work so well for other cancers do not work at all for prostate cancer. Several vaccines have been tried and failed in prostate cancer:

ascopubs.org/doi/full/10.12...

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

ncbi.nlm.nih.gov/pmc/articl...

pubmed.ncbi.nlm.nih.gov/351...

Based on all the above, it is highly doubtful that cholera vaccine, which is not even targeted to prostate cancer antigens and has no dampening effect on Tregs or tumor infiltrating macrophages, would have any effect. But ever-hopeful trials continue.

LapisLazul41 profile image
LapisLazul41 in reply to Tall_Allen

llllll

Cateydid profile image
Cateydid

Thank you, TA.

CAMPSOUPS profile image
CAMPSOUPS

The "association" flaw seems so prevalent from my wife to many intelligent men and women here.It almost seems like an inescapable human psyche flaw that requires a lot of diligence to self recognize.

However if true that is not a free pass for the many (youtube, internet,book deals) who proffer treatment recommendations knowing the flaw exists both in the studies they submit and within the audience they speak to.

Tall_Allen profile image
Tall_Allen in reply to CAMPSOUPS

There is a term for this cognitive bias in latin: post hoc ergo propter hoc. It translates to: "after this therefore because of this." In Research 101 we are taught this cognitive fallacy. But being human, we seek patterns even if there are none. "Cause and Effect" is a lot harder to show than mere Association, and because this kind of thinking is hard, we often jump to this error. The philosopher Immanuel Kant in the 18th century espoused that "cause and effect" is the inescapable lens through which humans view the world and results in our perception of time and space.

CAMPSOUPS profile image
CAMPSOUPS in reply to Tall_Allen

Almost a separate reality.

Tommyemily profile image
Tommyemily

Absolute words of wisdom, however it is an unfortunate truism that desperate people will grasp at anything that gives them hope and thus fall prey to those who take advantage of their credulity.

Boywonder56 profile image
Boywonder56 in reply to Tommyemily

Searchin for a rainbow.......

billyboy3 profile image
billyboy3

You are so right TA. I spent a great deal of time and energy in attempting to limit or reduce the crap that too often appears but nothing has been done to at the least minimize this sad state of affairs. It has reduced the power and influence of our site as well as has allowed far too many to post anything. The saddest result is the negative impact that some posts have in influencing some men to try these adhoc useless treatments, ie looking for the magic pill that WE know does NOT exist!!!!

SO, hopefully before I drop, our admin group will see how harmful allowing these posts to be placed.

Lastly, thanks TA, you have done a great service to so many!!!

Tall_Allen profile image
Tall_Allen in reply to billyboy3

I don't presume to speak for Darryl, but I think that to legally protect Malecare, he cannot interfere. We are all just equally patients and our posts are just our opinions. But once Malecare starts endorsing one over another, they would be practicing medicine.

in reply to billyboy3

Problem is that the "admin group" you speak of may decide that a post they don't like/agree with should be spiked and not published. This post could contain information that later is proven correct.

After all, Galileo spent much of his life under house arrest for saying what is obvious now, that the planets orbit the sun. This would have been spiked under your rules, for non conformity.

So better to publish everything, and let the reader sort out the wheat from the chaff

jackcop profile image
jackcop in reply to billyboy3

I think it is the patient's (us) job to research the treatment plan and move appropriately. As Tall_Allen says: "Once Malecare starts endorsing one [post] over another, they would be practicing medicine." I know Darryl thinks about this concern and does little to "interfere" which, in my opinion, is the only thing he can do.

in reply to billyboy3

Perhaps you would want a SOC-only group and a SOC/research group.

I can learn everything I need about SOC from my MO and clinical trials. Personally, I am more interested in research. But I can understand someone's desire to only entertain FDA-approved therapies and not have confounding articles/studies thrown in the mix.

Tall_Allen profile image
Tall_Allen in reply to

Many patients on here are enrolled in clinical trials that are not SOC, but are still within reach of the scientific process. I think what you are talking about is a pseudoscience group, where members encourage others to be guinea pigs with no hope of acting within the scientific milieu (without random assignment, adequate power, and control groups there is no hope of doing medical science).

in reply to Tall_Allen

Your view of the scientific process is incredibly rigid and reminds me of some dark historical periods. Any divergence from what was considered the norm was stamped out.

Research is not "pseudoscience". Speaking of "pseudoscience" please tell me when I said "pseudoscience" or when I so much as hinted at cultlike activities where members encourage each other to be some type of human guinea pig?

Research does require thought and this is a challenge for people who like rote memorization and are confused when it comes to real scientific rigor and advancements.

Tall_Allen profile image
Tall_Allen in reply to

My "view" of science, as you call it, has been developed over the last 600 years (since the beginning of the Scientific Revolution). It involves hypothesis generation, testing of hypotheses using methods that everyone can agree upon, exposure to a scientific community and acceptance or rejection of results. Results build and accumulate. Science subsists because it has proved to be so flexible, not rigid as you think.

Anything outside of science that sounds "sciency" (but isn't) is pseudoscience. Here are the characteristics of pseudoscience:

prostatecancer.news/2021/07...

You are advocating research on patients ("guinea pigs") outside the norms of science or ethical responsibility. You are also saying that the methods for determining scientific truth are inadequate. I agree with your suggestion that those interested in creating such new truth claims should form their own forum.

in reply to Tall_Allen

Since you like history: eurradiolexp.springeropen.c... "everyone" doesn't include the ASA. Yes, true research requires original thought. Not comfortable for everyone (hint, hint).

Your approach is both rigid and incorrect.

I asked a question and then stated that I like to research. I am still at a loss to how you managed to decide that this means that I am an advocate for research on patients ("guinea pigs" in your terms). There is nothing wrong with asking for clarification.

Ok, now you may have the last word. I have learned that you will keep on spouting nonsense until eventually, you exhaust your opponent.

Tall_Allen profile image
Tall_Allen in reply to

That link doesn't work. But I am now reading "The Constitution of knowledge: A defense of truth" where Rauch goes through the history of how we as a society have come to judge what is true.

No need for your silly hints. I am very comfortable with hypotheses, right or wrong. It is only when people become convinced their hypotheses are true with inadequate evidence that I have a problem- or I should say when they do others harm by trying to convince them that potentially hypotheses are true (hint, hint).

" I am still at a loss to how you managed to decide that this means that I am an advocate for research on patients ("guinea pigs" in your terms). " You wrote: "I can learn everything I need about SOC from my MO and clinical trials. Personally, I am more interested in research." How does one patient do "research" unless he uses himself as a guinea pig, as you have written elsewhere you are doing?

jimreilly profile image
jimreilly

Thanks Tall Allen -- maybe a good way to stay healthy is to BE a healthy traveler, lol

Jimbo59 profile image
Jimbo59 in reply to jimreilly

Have done a LOT of travelling since my 2015 diagnosis.! Feeling pretty healthy too...

MarkBC profile image
MarkBC

Very wise words of advice. Thank you Tall Allen. I am so appreciative of all your posts. They have been so helpful to me during the past 4 years of dealing with this disease.

kapakahi profile image
kapakahi

Thanks, Tall Allen. Re: metformin: so that's why my SHBG level is so high and free T is so low! I had no idea. (I take metformin for pre-diabetes.)

As for the human fondness for pattern-seeking: the cloud that looks like George Washington isn't really George Washington.

compiler profile image
compiler

I have taken metformin for about 8 years as per Dr. Lam. I'll have to discuss this at length at my next appointment. Also, TA, you alluded to SE. For the past year I have had increasing lower intestinal gas. Usually drug SE develop fairly soon after starting a drug. Can SE commence even after a long period on a drug?

Mel

Tall_Allen profile image
Tall_Allen in reply to compiler

Idk - but it is certainly a known side effect of metformin.

in reply to compiler

Yes. As we aren't able to take the stresses that we could when we were younger. My PCP told me this many years ago.

Karmaji profile image
Karmaji

I agree with TA that random trial clinical studies give us a general sound basis.However, then journey of each human facing PC is different for same initial symptoms. Personally as a scientist I respect the knowledge based on verified studies .

We have to go for adaptive therapies and go for medical thinking which removes the cause of disease. Actually, medical treatment are oriented toward curing the disease whereas the causes remain hidden.

We the patient can take our health in our hands by having a mindset of removing the causes which is linked to our lifestyle.

Key is integration of medical know how, questioning it, diet therapy, exercise therapy, mind therapy and an integrative approach....an art of staying healthy.

Sure, when a house is on fire, we have to extinguish the fire but not destroy the house.

Lrv44221 profile image
Lrv44221 in reply to Karmaji

Well written. I too have science degrees, the last one being a board-certified nutritionist.I have always thought "kill the disturbance at the root". not just cover the symptoms.

although our physicians are helping, thank goodness, I feel we too, can assist.

we all have different needs but the ones I i believe help are:

Oxygen (walking, moving, dancing, swimming, etc.).,

Diet (no sugar)

Sleep and/or Rest

Nutrients. ( Vitamin D3, Beta Glucans) and others depending on your individual bodies need.

I love this site as it helps me so much and i hope I do not offend anyone with my comments,

Thank You, LRV

Tall_Allen profile image
Tall_Allen in reply to Lrv44221

I wish we knew the causes - they are probably myriad. I always exercised and ate healthy. Maybe good for my heart, but it didn't seem to affect cancer.

Karmaji profile image
Karmaji in reply to Tall_Allen

a mystery......I was looking at epigenetic aproach to cell mythylation....more global..

Tall_Allen profile image
Tall_Allen in reply to Karmaji

Sometimes methylation is beneficial, sometimes deleterious. If it were an easy problem, it would have be found many years ago.

Karmaji profile image
Karmaji in reply to Tall_Allen

Agreed. I was reading bookYounger You

by Dr Kara Fitzgerald

Found interesting where methylation

may be rightly handled thru adaptable diet

Lrv44221 profile image
Lrv44221 in reply to Tall_Allen

Same as my husband's cancer, so frustrating

cancerfox profile image
cancerfox in reply to Tall_Allen

This is a sore point with me. I also tried to always eat healthy as possible, exercise regularly, never smoked, very little alcohol use, no drugs, always used sunscreen, did all the things they tell us to do and boom!...prostate cancer anyway. Obviously cancer isn't always following the script we are promoting, and is just random or inevitable in a lot of cases as far as our current knowledge can ascertain. All the anti-cancer advice we get from food experts, fitness promoters, etc. may decrease the chances of getting cancer but doesn't prevent it. 🙁

in reply to cancerfox

I also ate well and exercised. The way I look at it is that doing the wrong things might have put me in the morgue from a heart attack. And if that didn't happen, perhaps my Gleason 9 would have been a 10. Perhaps my T3b/c would have been stage 4. Perhaps I would have had bone mets. Perhaps I would already be dead. Who knows?

I am where I am today and eating healthy and exercising regularly is what I do. Am I going to rely solely on diet and exercise to eradicate my cancer? No. But I enjoy them and I don't think that they would hurt and might possibly even be helpful.

cancerfox profile image
cancerfox in reply to

Or eating healthy and exercising may have actually supercharged the prostate cancer for all we know. I agree with you that a healthy lifestyle probably improves your odds against heart disease, diabetes, etc., but when it comes to cancer it's more like we are just playing Russian roulette.

in reply to cancerfox

Interesting. My MO told me the opposite. I used to work out a half-hour a day and she asked me to increase that number. I didn't ask her about diet. I never considered that healthy eating exacerbates cancer. I'll ask her next time I see her.

TylexGP profile image
TylexGP in reply to cancerfox

Reminds me of the Woody Allen Movie Sleeper. When they tell him Cigars and steak have been good for you.

I have spent a fair amount of my career in R&D and have seen improvements in cancer treatments (e.g. Immunotherapy), but not magic silver bullet. I personally don’t thing you will find one all you have to look at the complexity of cell to cell signaling and all the different and redundant pathways in just that micro environment to understand the complexity. Ideally we will eventually develop enough tools that we can take each individuals pca and develop a personalized and effective plan. We see glimpses of that now and hopefully it will continue. Sorry for the long post.

dhccpa profile image
dhccpa

I have no problem with what you say as written here in its totality.

larry_dammit profile image
larry_dammit

Thanks for keeping a sharp eye out for us, I always look at this stuff with caution, if it was true my Doctor and I would already be on top of it .

tallguy2 profile image
tallguy2

Thank you. Well-written and truthful.

EdBar profile image
EdBar

Studies and trials posted on this site are very interesting and informative and may lead to questions during doctors visits, but they also can be flawed and misleading. I’ve had that pointed out to me by Dr. Sartor on more than one occasion.In the end I go by what my doctors tell me. Metformin, for example was originally prescribed by Snuffy Myers for me years ago. Dr. Sartor, my PCa specialist after Snuffy retired reviews my meds every six months and never once questioned me taking it, in fact during my last visit he told me what he tells me all the time”keep doing what your doing” it’s working.

Ed

in reply to EdBar

As you know I have gone way out of the box. I sort of follow SOC therapies but change them for me and my life. My MO seems impressed with the results so far and the only questions she asks concern why I decided to do certain things. Kind of a learning experience that goes both ways. And she also says "keep doing what you're doing because it's working". Lately, some of her responses to my latest "adventures" almost remind me of the cheerleaders in High School: "keep on keeping on" and "go for it, Russ".

I like reading clinical trials and get some good info from them. But frequently I see a responder to a studied therapy yet the overall average doesn't meet statistical significance so the therapy is deemed a failure. Really bothersome if doesn't quite meet the arbitrary definition of 5% probability of random chance but trends to significance and is highly significant for some people. And not much thought about side effects and cost (risk/reward). Apparently, 5.01% is nonsense but 5.0% rules the day! How about 6%? Terrible!

We all like the comfort of nice cozy rules. And they can work... some of the time, and following them blindly enables us to avoid that dirty thing called thinking.

Bottom line, I study the studies and am not swayed by "significance" if there is little or no biological plausibility. And if I see a p-value of 0.06 (or even higher), I look into it; yes that means I need to think. Two things that are very much lacking in the simplistic p-value approach that many use are cost and side effects. Given two therapies, one with a p-value of 0.05 for CSS and horrible side effects and a huge financial cost and the other with a CSS p-value of 0.06, very few side effects and a tiny financial cost, am I to believe that I should knee-jerk go for the former? And then there is the effect size and subject variation. I won't even go into those.

I used to work for a medical company and did a couple of stints for space and defense companies. If failure of a mechanism resulted in possible or probable mortality we would reduce that p-value from 0.05 to 0.005 for quality screening purposes. If something would result in a possible user annoyance, the R&R metrics would become very open. Sometimes we'd even open them so wide that a bus could drive through them so that we could spend time where it mattered. On our medical staff, we had two full-time professional statisticians. Their opinion was that the p-value while important, was arbitrary and could only be used as a crude screen.

Fascinating how I see the mentioned confusion in many people. I even expect the possibility of some blow-back from confused individuals who want the tidiness of rules instead of the messiness of thought. The American Statistical Association (amstat.org/) explained it better than my lame attempts:

"According to Wasserstein et al. [6], the statement statistically significant has today become meaningless. In 1885, Edgeworth’s original intention for statistical significance was simply to have a tool to indicate when a result warrants further scrutiny; statistical significance was never meant to imply scientific importance, but that idea has been irretrievably lost [7]. Yet a century later, the confusion persists. Such doubts can lead to radical choices, such as the one taken by the Editors of Basic and Applied Social Psychology, who decided to ban p values in 2015 [8].

Wasserstein et al. [6] also say that “no p value can reveal the plausibility, presence, truth, or importance of an association or effect”. Therefore, a label of statistical significance does not mean or imply that an association or effect is highly probable, real, true, or important, nor “does a label of statistical nonsignificance lead to the association or effect being improbable, absent, false, or unimportant”. Furthermore, this false split into worthy and unworthy results leads to the selective reporting and publishing of results based on their statistical significance, the so-called publication bias. Similarly, Wasserstein et al. [6] also suggest to stop using confidence intervals (CIs) as another means of dichotomisation, based on whether a null value falls within the interval. However, despite these considerations, the ASA does not recommend to stop the p value calculation. The two sides of the debate may be conciliated. Just, when p values are used, they should be reported as continuous quantities, not claiming significance or non-significance. The ASA position may be summarised with the sentence “as statistical significance is used less, statistical thinking will be used more”."

Statistical significance: p value, 0.05 threshold, and applications to radiomics—reasons for a conservative approach | European Radiology Experimental | Full Text

eurradiolexp.springeropen.c...

middlejoel profile image
middlejoel

Adding to the confusion, I also take metformin, recommended and prescribed by Dr. Dorff.

wilcoxsaw profile image
wilcoxsaw in reply to middlejoel

As does Mark Scholz

Tall_Allen profile image
Tall_Allen in reply to middlejoel

Even doctors are not immune to bad science.

Cooolone profile image
Cooolone in reply to Tall_Allen

^^^THIS^^^

And Bias, especially when it's something they thought of, lol...

in reply to middlejoel

Yeah, I'm an ignorant rebel. I take metformin too.

Runner4000 profile image
Runner4000

Thanks for the thoughtful reminders, TA.

Wdoug profile image
Wdoug

Thanks for all your help and support throughout the last several years, I am one of the extremely fortunate APC patients who used the site as support through radiation and the 4+ years of ADT. Support was needed and appreciated through those years of continuous tiredness and the other side effects which became routine. Just had my recent blood test which was 0.04 PSA and they didn't even check the Testosterone which was below 10 for 4 1/2 years and 6 months ago was 300+/-. I'm now 78 instead of 71 and am so happy the radiation and Lupron were effective for me with no other alternatives required. Wish everyone had fortunate results I had, but You, as the site's watchdog, can continue to support and guide others.

Currumpaw profile image
Currumpaw

T_A,

Everyone has a favorite study. Within the study below it is found that Metformin increases telomere stability. The telomere --the blueprint for a new cell to replace a dying cell.

Metformin: A Potential Candidate for Targeting Aging Mechanisms

ncbi.nlm.nih.gov/pmc/articl...

Currumpaw

ADTMan profile image
ADTMan

To play devil's advocate, take the case of stomach ulcers. A researcher from Australia thought it was caused by a bacterial infection and the entire medical community said it was caused by excess acid. He went against the conventional wisdom and won the Nobel prize. (I wonder why I can't find Maalox around anymore).

Of course, the medical community eventually came around and the scientific method proved it. However, what if no one got around to doing the necessary trial/studies. Nevertheless, a one out of a thousand chance that an unproven therapy will work is no reason to pursue it.

Tall_Allen profile image
Tall_Allen in reply to ADTMan

That actually PROVES the point - good, well-done science is what creates advances.

ADTMan profile image
ADTMan in reply to Tall_Allen

Yes, absolutely. BUT, it took several years of insults and the huge resistance of the medical community to accept it. I guess the point is that acceptance of new ideas can take a long time. Obviously, there are other examples and yet to be discovered examples and that may be the problem with some people going outside the mainstream for unproven treatments. I'm with you - don't do it.

Tall_Allen profile image
Tall_Allen in reply to ADTMan

Mainstream opinion changes BECAUSE of science, not in spite of it.

ADTMan profile image
ADTMan in reply to Tall_Allen

Yes, of course. My point is it can take years to become mainstream and perhaps in some cases never occur. The stomach ulcer case is a bad example because the answer was so unassailable. No so with prostate cancer; hence, the need to follow the mainstream even more.

anonymoose2 profile image
anonymoose2

We old timers remember “When E.F. Hutton Talks, People Listen”And when TA talks on this site “We members Listen”

As always TA thank you for your wisdom and input!

Currumpaw profile image
Currumpaw in reply to anonymoose2

You might not want to use EF Hutton as a standard of excellence and ethics in the future.

From Wikipedia:

"Hutton retained Tom Curnin, a respected defense attorney who was inclined to fight the government. However, in February 1985, Curnin discovered a memo from a Hutton regional vice president for the Washington, D.C., area which stated that his offices drew on "bogus deposits". The memo—tantamount to a smoking gun—led Curnin to change tactics and begin negotiations for a plea agreement. In the spring of 1985, Curnin told Hutton's board that it faced two choices: plead guilty to a massive list of felonies or face a trial that would likely see three senior Hutton executives convicted and drive Hutton out of business. Curnin advised settling with the government to avoid years of bad publicity.[5]

On May 2, Hutton agreed to plead guilty to 2,000 counts of mail and wire fraud, as well as pay a $2 million fine plus $750,000 for the cost of the investigation. This is equivalent to approximately $4.2 million and $1.6 million, respectively, in 2020.[7] Hutton also agreed to pay $8 million in restitution—the estimated extra income earned from the fraud. This is equivalent to approximately $16.7 million in 2020.[7] In return, Curnin wrung two major concessions. First, no Hutton executives would be prosecuted (even though the government determined that 25 senior officers masterminded the scheme). Second, the Securities and Exchange Commission allowed Hutton to stay in business; offenses of this magnitude usually result in an individual or firm being permanently barred from the securities industry.[5][6]

An internal review conducted by former Attorney General Griffin Bell concluded that the scam occurred due to inadequate internal controls."

A dear friend of mine worked at a commodities brokerage in Boston in the late 70's and early 80's. She saw activity she did not want to be associated with, found another position and gave her notice about six months before the Feds walked through the doors. I certainly did miss her. She was, "simply irresistible". Careers create distance.

Currumpaw

anonymoose2 profile image
anonymoose2 in reply to Currumpaw

It was intended to be humorous As the commercials were intended to be at the time.

youtu.be/AetDSsgrWWk

Flydoggy profile image
Flydoggy

Solid advice, as always. Thanks

Lrv44221 profile image
Lrv44221

CAREFUL and CAUTIOSThank You for all your posts. I myself, tend to be a little "too eager" to follow what others have suggested., including my thoughts You are right, we need to be careful about things other than the treatment our oncologist has recommended

Gabby643 profile image
Gabby643

Thanks T A!

jackcop profile image
jackcop

Thanks, Tall_Allen.

j-o-h-n profile image
j-o-h-n

Includes Humor?

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/26/2022 8:16 PM DST

in reply to j-o-h-n

You need to run humor through a clinical trial. If the humorous p-value is less than 0.05 then submit the joke to the FDA. If it is eventually approved, you may post your humor.

j-o-h-n profile image
j-o-h-n in reply to

Thank you, I like your style...... Good Idea....FDA = Funny Dumb Ass humor predicktors...

God Bless our past and current military service personnel.

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 05/30/2022 7:43 PM DST

marc_andersun profile image
marc_andersun

Keep up the great work, TA! Your work saves me a lot of money, and keeps foolishness at bay.

Purple-Bike profile image
Purple-Bike

I believed the Swedish study had done such a good job of weeding out con-founders that I could neglect the advice I have gratefully learned from TA about the limitations of retrospective studies. But the new study TA and Patrick refer to indicates that there is indeed a real confounder to the Swedish study, that of the healthy traveler.

I agree with TA that this is a more likely explanation than the hypothesis put forth by Schwah, that of some but not all vaccines somehow revving up the immune system to battle (prostate) cancer. I wouldn´t rule out the latter entirely, though. I cannot vouch for their relevance maybe they are bs, but see e.g. this overview from 2021

infectagentscancer.biomedce... and

pennmedicine.org/news/news-...

The study shown by TA shows that vaccination for hepatitis A and B did not show any reduction in HR, and acknowledged that this was a point in favor of a real effect of the cholera vaccine.

In any case, I am looking forward to my next cholera vaccine, for its immense boost to my lymphocyte count, 80 % up when I took it, which surely is not mainly caused by con-founders 😊So I am also grateful to have learned about the Swedish study on this site, in connection with which I learned about the lymphocyte boost. If there is an anti-PCa effect, it would be great, although I realize the odds are considerably worse after understanding the new study.

Let´s keep on learning this site is just great!

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