Wednesday, January 29, 2020
Clinical Trials ~ Lies, Damn Lies and STATISTICS ~ and data we need for melanoma decisions and treatments...
We all need real live data, proven factual information, in order to make reasonable choices about our health, needed treatments, medication, safety information on the vehicles we drive, the restaurants at which we choose to eat, and ever so many other daily decisions - large and small! Data is important and should not be buried or fudged to attain outcomes preferred by invested parties. When you are diagnosed with a deadly disease, you need real, tangible information in order to make the best informed decisions you can regarding your care. I wrote this in 2012: Educated guesses and desperate decisions..... Being a rattie in a Phase 1 clinical trail of Nivolumab (Opdivo) from December 2010 - June of 2013 was an extreme learning experience to say the least! As a medical professional of many years, always accompanied by another, I am horrified to think of what folks without out such backgrounds deal with in that circumstance. As it was we were definitely swimming upstream during that process! And while I am certain access and participation in that clinical trial absolutely saved my life, the management of clinical trials runs the gamut from incredible science to completely ludicrous to intensely horrifying! Here are just a few of my rants regarding clinical trials over the years:
July 2013: Almost 50% of Results of Cancer Drug Trials NOT published!
March 2014: Should Melanoma Brain Met patients be allowed in clinical trials???
April 2014: Clinical Trials and Patient Rights...An oxymoron????
December 2014: Patient rights in a clinical trial. An oxymoron???? Redux...
January 2015: A beautiful lady, with eloquent, though heartbreaking words re: clinical trials....
January 2016: The Problem with Clinical Trials
August 2016: Medical studies in children go unpublished!!! Here we go AGAIN!!!
September 2016: New Rules to push for published trial results!
January 2017: The trial of trials!
June 2017: Outcomes for melanoma patients ~ clinical trials vs standard of care
April 2018: Odds and Ends ~ Melanoma in children and cancer trial access for people of color
Sadly, many of these reports touch on points that remain unresolved! Just last week, Medscape posted: Most Clinical Trials Still Don't Report Results by Deadline Despite the many lives at stake, the report notes: "Three years after a federal deadline was clarified, mandating that clinical trial sponsors report results to ClinicalTrials.gov within 1 year of the primary completion date, most researchers still miss the deadline, ... [To examine this issue, researchers] ... downloaded all registered trials due to report between March 2018 and September 2019 and found that of those 4209 trials, only 40.9% made the 1-year deadline; only 63.8% reported results at any time."
Horrifying, no?? And even when researchers report trial findings, what do those results really mean? Does 1 + 1 really = 2 mathematically??? Sometimes not!!! Back in March of last year, 800 scientists signed a group letter calling for an end to ridiculous statistical massaging of data. Here's a report on their thoughts from Nature: Scientists rise up against statistical significance The authors note: "For several generations, researchers have been warned that a statistically non-significant result does not ‘prove’ the null hypothesis (the hypothesis that there is no difference between groups or no effect of a treatment on some measured outcome). Nor do statistically significant results ‘prove’ some other hypothesis. Such misconceptions have famously warped the literature with overstated claims and, less famously, led to claims of conflicts between studies where none exists." Noting that in the end it was their hope, that - "Decisions to interpret or to publish results will not be based on statistical thresholds. [rather] People will spend less time with statistical software, and more time thinking."
And if the math and conclusions involved are reported AND meet "statistical" and "common sense" significance, does the issue or the drug examined even matter? I could write reams on the first. Studies that look at obvious issues and derive obvious conclusions, like: "Folks who consume more calories weigh more than those who don't!!!" or "Children whose parents spend more time with them do better in school and life!!" or "Peeps who eat their fiber POOP!" Real studies people. Wouldn't even kid you!!! Apart from that - are the treatment or drug options developed and studied even needed? Unfortunately, there are many instances when you could argue - NOT!!! This opinion piece from September 2019 in STAT, touches on that very point: Enough with the me-too drugs. New treatments should be worthy of the people who invest their lives in clinical trials
"...I believe are too many companies pushing mediocre and me-too drugs, also known as copycat drugs, into clinical development where they will likely fail. Clinical trials are more than a way to test new therapies. They offer very sick people hope and a chance for more time with their loved ones. Lately, the drug development process has turned into an exercise in me-tooism — at patients’ expense. It’s time to shift the focus back to those who matter most." With the author noting that in a panel discussion, the head of the FDA - "called for companies to reevaluate their current clinical trial processes. He rightfully criticized the industry’s repeated attempts at testing an approach in a disease indication after it has failed multiple times. [As an example, he pointed out] ... "checkpoint inhibitors (drugs that target PD-1 or PD-L1) for multiple myeloma. Three recent studies were conducted close together, and although they were well-controlled and well-managed with data safety review boards, multiple studies showing negative results were not needed... There is no question that replicating studies has value, but in this situation the industry was duplicating harm to patients, as all three studies showed decrements in overall survival. ... When people enroll in cancer clinical trials, they are placing their lives in our hands. Many have advanced disease and turn to a clinical trial for hope and possible healing. Yet as an industry, we are competing for these patients to test me-too drugs with significant toxicity, sometimes based on marginal preclinical data. ...patients are not a company’s resource. ... They are people who are hoping for a chance at recovery, or at least more time with their families with reasonable quality of life. We should treat patients who volunteer for clinical trials the way we would treat our mothers or husbands or best friends. [He] asked companies to be more efficient by collaborating, sharing data, and conducting platform trials. Some biopharmaceutical companies are trying to do this, but the industry has a long way to go. We should be moving drugs into clinical development only when there’s a strong understanding of disease biology and substantial evidence that a drug has the potential to truly improve lives."
Even when trials meet all of the desired criteria - how does the information attained address the individual? After all, it is pretty clear that the disease process and treatment response (in terms of disease control and adverse events) varies greatly person to person despite group outcomes. In the summer of last year, The Scientist published this: N-of-1 Trials Take on Challenges in Health Care, where the author notes "... an N-of-1 trial [is] focused on the collection of treatment-response data in a single patient, this relatively little-used trial design represents the ultimate form of patient-centered medicine." Pretty interesting stuff and probably most valuable in tweaking care for a particular patient though they could also elucidate trends when similar results are found among multiple individuals.
So, if you're still with me - and still need to find a clinical trial option that is right for you, there remains the difficulty of learning about available trials and dealing with all the "exclusions" once you've found a trial that seems as though it could be helpful. If you've already had this medication or that one...you may be excluded. If you can't do the prescribed number of jumping jacks...then nope. This trial is not for you. For the longest, folks with brain mets and CNS disease were kept out of melanoma trials. Why???? If you are seeking care for a hang nail, then perhaps participation in an experiment with a medication that may cause awful and at times lethal side effects would be over-the-top and ill advised. However, if you are going to DIE (no doubt about it) without effective treatment, shouldn't those peeps be allowed access to experimental treatments if that is what they want to do??? (Yes, several states now have "Right to Try" laws, but even when patients attain care under their cover, insurance companies, often say, "No thanks, you're on your own!" which shuts down access right then and there!) Or, do we simply exclude those likely to have untoward outcomes because of their advanced disease, limited physical strength, or prior treatment failures so as to prevent poor statistical results that will reflect badly on the institution, researcher, or BIG pharma who happens to be running the trial? In prior rants included above, I've noted that researchers can easily group such patients in an arm of their own so as to clarify outcomes. In the category of ~ for what it's worth ~ I saw this in Forbes: Developers Use Artificial Intelligence To Match Patients To Clinical Trials
Despite all that is difficult, negotiating and participating in a clinical trial IS doable!! Even if you have to do it on your own. Here are some thoughts I put on MPIP for a forum member not too long ago:
I was lucky. But, you can be too!!! Ratties rule!! Blessings to each of you. - celeste
Monday, January 27, 2020
Per yesterday's tale, we made our way from RI, through CT, and into NJ while avoiding driving through NYC this go round, to the NJ Enterprise car drop off at the Newark airport. Despite the strange labyrinth of streets surrounding it, we arrived at 4 pm that afternoon. An odd hefty fellow, bearing a strong resemblance to a bull dog, checked us in. He behaved oddly and inattentively throughout - often directing his gaze over the expanse of cars, then distractedly peering back at us and his handheld electronic device. Once asking, "So this is your second car?" "No," we said, "this is the same and only car we rented in D.C." He replied that didn't make sense while re-scanning the car with his do-dad. He dealt with some other people. Didn't say much else, except that we could go. Feeling rather confused about such a process, we were directed to the 'air train' that would take us to the airport and a shuttle to the Newark Holiday Inn. The room was pretty basic but it was funk free with none of the B and B creepiness!!!
Next morning, after a good workout, we were off. The trip into NYC was a bit more complicated and time consuming than anticipated ~ Shuttle to the air train. Off at P4. Take escalator to NJ Transit station were you buy a ticket for a variable fee of $11.25 or $15.25 one way. Reasons for pricing vagaries were never entirely clear. THEN - after a strange and dirty train ride, where there is no absolute clarity provided that you are on the right train, you pass on by the Seacaucus and Newark Penn Station stops, but get off at NY Penn Station. Cause, you know? Confusingly similar names is GOOD! At Penn Station we went to the subway station for a pass to head "uptown" toward the Met. We arrived at Lexington Station at 1 PM. NO, I had NOT had breakfast! But B and Le Pain Quotidien to the rescue with yummy croissants and coffee! Nectar of the GODS, I tell you!
In keeping with the need to get in our exercise and maintain our rep for an authentic Morris Vacation, we walked over 20 BLOCKS out of our way and had to turn back the same 20 BLOCKS to get to the Met, though SOMEBODY had been told by ME that we were going past our desired street!!! Oh, well. T'was a Morris Vaca after all. Still, we were a bit tired when we arrived at the museum after a 2 hour walk! We had fun exploring the Greek and Egyptian exhibits, lovely Cassatts, and an exhibit from an artist unknown to us - Felix Vallotton - that B liked because of his use of composition and darkness as well as an amazing display of Dutch Masters that I LOVE because of their use of light and life!!!
We had a great dinner at a little Turkish restaurant I had read about - Beyoglu.
Given the efforts we expended AFTER exercising the day prior, we decided to take a pass on that effort the next day and headed out. We managed our commute with minimal difficulty, heading straight for Best Bagel!!!
|Even snagged a chair and counter space as B ordered. Still delicious!!!|
Back on the shuttle once more next morning to catch the flight home - at the butt crack of dawn, of course!!! Our flight took off late, spitting us out at Concourse B in Atlanta for our connecting flight at Concourse D to Chattanooga. We took the train to D and began running. Just rounding a corner while trying not to trample folks I heard the last call for boarding, as well as a woman's voice yelling, "CHATTANOOGA! CHATTANOOGA!!!" I breathlessly arrived at her stand, to see it was all buttoned up! I gave her my name, telling her I was there to board. With great annoyance, she asked, "Where's the other one?" I point toward B, still struggling toward us. Shaking her head with great disapproval, she said, "Where's your boarding pass?" "With him," I replied. "Where y'all been?" the irritation queen queried. "We just landed!" I told her with equal irritation. A fact she was surely aware of as she knew to expect the two of us! B finally arrived, turned over our passes, and we walked on to the very back two seats. On arrival to Chatt Town that afternoon, I was surprised to see our bags actually made it!
Meanwhile in New York, and for days after, we (and Roo - as we had given her number for the required emergency contact) were relentlessly harangued by Enterprise for not having turned in the horrible nasty Corolla!!! To the point that we stood accused of having to answer for having stolen it! Yes, that's what car thieves do ~ provide their address, phone numbers, driver's license, and credit card info to the people you steal the car from!!!! Seriously??!! Finally, after being very plain spoken about Mr. Bull Dog Man at the Newark check-in and that they had best get off our case - the calls finally ceased! I believe I've mentioned my loathing of all car rental companies in this space previously! They have yet to change my mind!!!
All the strangeness not withstanding - thanks for another wonderful adventure, B!!! Where are we heading next???? Travel chaotically!!! ~ les
Sunday, January 26, 2020
More exercise and "eatmeal" (Fred-o's name for oatmeal in childhood - makes sense right?) for an excellent start to our day! Sad how little used the exercise rooms of hotels seem to be! Then we were off on what B deemed to be the most scenic route from Fishkill, NY to New Haven, CT for a meet up with another dear J at Frank Pepe's Pizzeria! Golden trees decorated our path despite the clouds.
Great eats with great peeps! White Clam Pizza along with Frank Pepe's original tomato pie! But as ever, the real treat was being witness to the incredible resilience of the human spirit, the traumas and triumphs that all too often remain unheard - but on special occasions are burdens shared - like a gift - between those who once were strangers, but are now friends. You are incredible, J. Thanks so much for sharing YOU, with me!
After our nice lunch and visit, we were on the road again, heading for a "lovely B and B" B had reserved in Narragansett, RI! There was distinct foreshadowing of what was to come, when during lunch B received a strange call from someone who initially failed to identify themselves, asking if we were still planning to arrive and when. Ummm - yes. And, as there was no stipulation for a specific check-in time - when we get there!
I hardly have the strength or words to explain the creepy that was Sheppard's Place B and B!! Suffice it to say that the guy "running it" appeared to be stoned out of his mind on our arrival. When we could not find it around dusk, we called him for assistance, giving him our precise street and exact location - which turned out to be directly behind the house!!!! He could not give us ANY helpful pointers at all!!! We found the house ourselves, the front being hidden by a large hedge and the sign beside the drive that entered the hedge as a crescent, being very small. Turns out we were the only guests that night. It was pretty clear that he was hoping we would not be showing up! His assistance and information was equally lacking in any direction toward a place to eat supper. He gave some reference to "lots of places down that street". The place was clean, but between him and the decor - strangely creepy. It was already over decorated with wreaths and fake flowers and copies of paintings by the old masters and books and lamps and doilies on EVERY possible wall and surface. Fake vines twirled up most pieces of furniture! THEN, as if that was not enough, there were skeletons, pumpkins, witches, spiders, webs, and all manner of Halloween decor thickly spread on top of that!!! Later we determined that stoned dude was "running the place for my mom". Throughout the night there was a great deal of coming and going by the dude and his bud. So, we got little sleep and when we did, we both had nightmares!! B going so far as to awaken me when he shouted out in terror!! It is truly the only place where we have arranged to stay that I almost made B leave - whether we could get our money back or not!!! Anyhow - we survived!!! HA! The next day we were up and outta there. We drove along the RI coast and had a walk along a trail by the ocean. Very pretty even with the clouds in this off season.
|Bittersweet, I think!|
More on TURNING THE CAR IN to Enterprise, NJ, and NY coming your way tomorrow!!! Travel chaotically! - les
Saturday, January 25, 2020
B and Google saved the morning. After our stinky night, breakfast at Hightstown DINER, set our day off right. It was incredibly busy, but the staff was amazing and energetic. Our young waitress certainly deserved more than her pay! Delicious pancakes for me, egg white omelet and turkey bacon for B. He's so good!! Then again.......
To back up a step! Back in our foul hole the night prior, we meticulously planned our route to Fishkill, NY - assiduously avoiding NYC or the George Washington Bridge! Why then, you might ask, do I have this?????
Because my navigator loses his mind periodically!!! And that's not good!!!! I traveled over a bridge I expressly asked to avoid during a POURING, FLOODING, DELUGE!!!!!!!!! Oh, my! Imagine driving through crazy weather, on a multilevel bridge, during NYC rush hour, in a nasty ass Corolla with a wonky left front wheel that did not behave as expected and made strange rubbing sounds, while listening to some gibberish about, "In my defense Google maps changed the route while enroute!!!" Along with sycophantic comments like, "Fortunately, excellent driving saved the day!" What a crazy boy! While difficult and unpleasant, (AND NOT WHAT I REQUESTED!!!) it was still not as bad as driving in Atlanta!
The drive through the Hudson River Valley was very pretty. Little towns with old fashioned squares and historic districts were bright with red and yellow maples. My vision of stopping and walking through them as fancy struck was stymied by the pouring rain, which was unfortunate. However, Sleepy Hollow, Ossining, and Tarrytown were most lovely and I would have loved exploring them more as we made our way to the Springhill Suites in Fishkill which was very nice and funk free!!!
Supper was a bit sad in a strip mall at Charlie Brown's Grill. Usual fare, served as imagined. But, exciting times as an old grey headed codger holding forth on a bar stool suddenly fell to the floor, seemed to have a seizure - but just as B and I were about to see if we could assist - he got up, finished his drink, ambled out, and I presume - DROVE (!!!) off!!!
Up early for exercise and oatmeal - both very refreshing and on to Beacon Falls to meet our dear friends F and J!!!
|Keeping it me-made, in prior jean jacket, nikko turtle, layered under a Sasha Basic instinct tee, all paired with yet-to-be-blogged Romero Trousers from the same pattern I used for Roo's shorts!|
|Two of the smartest, most convivial, adventure loving, amazing peeps you will ever be blessed to meet!!!|
Such a lovely place. Here's a cool video J shared via the NYT about the care involved in managing such a place: Who Mows the Lawn at Storm King, New York’s Largest Sculpture Park?
So great to share time with dear ones. So many lovely sights to be seen. Travel and live chaotically! ~ les
Friday, January 24, 2020
Across Maryland to the coast of Delaware!!! The theme of minimal humans and lots of farm fields continued. Gradually, the flats gave way to more picturesque rolling hills and we ended up here:
|...who had joined a couple of vultures for some fine dining on what appeared to be a deer carcass. Fancy friends in low places?|
Heading to New York tomorrow!!! Travel and eat chaotically! ~ les
Thursday, January 23, 2020
Only got a smidge lost on our walk to the Enterprise car rental. Was dealt with by a hale and hearty dude who was nice enough. Attained a beat up Toyota Corolla that could have been dirtier, though that would have taken a great deal of effort! (SO much more Enterprise drama later!!!) Anyhow - as they say - it is what it is!! And we were off. Not having traveled a block from the parkade we were almost crushed by a crazy old white man driving a large pickup. While we (and a long line of traffic before and aft) were parked at a light, he decided he was turning across traffic and INTO me!!! There was nowhere for me to go! There was nowhere for him to go! But, that DIDN'T STOP HIM!!! Good grief! Luckily (????) I managed to give him just enough space and he was able to squeeze between and jump over a curb! Old White Male Jerk-a-tude in action!!!
Meanwhile, this awesome old white dude - advocate for the world - and I, carried on. Down and through Maryland. Did you know there are very few people visible in or on most of the highways and by-ways in much of Maryland once you leave the coast?? Who knew? But, before that, we:
|Saw pretty harbors.|
|Walked on a board walk. (Wearing me made: Lander pants, previously noted Linden, and Nikko, mock turtle neck)|
|Saw pretty sights despite the cool overcast day.|
|Dinner! A rather sad affair at Buster's Seafood Grill in a strip mall that had come with glowing recommendations from the lady at the hotel reception desk. B, ever up for local fair indulged in broiled "rockfish" (local fish - white and rather dried out in this iteration) and "WET cornbread"!!! OMG! Don't. Just DON'T!!! Yes, I took a bite. Yes, against my better judgement and impetuous, spoiled nature, I swallowed it. It was indeed wet. It was incredibly sweet. It was - dreadful!!! You don't have to take my word for it. Check out this recipe: Wright's "Eastern Shore" Cornbread Recipe|
On to Delaware tomorrow!! Travel chaotically! ~ les
Wednesday, January 22, 2020
October was busy!!! After celebrating their marriage with Jamie and Roo, we took off - on a rather strange trip! Yes, one that I concocted!!! Though some things didn't turn out as planned (or imagined) it was still lovely to share it all together and with dear ones along the way!
|Arriving at the airport to find that our flight was delayed for over an hour and changed to a smaller than advertised plane can't get you down when your outfit is comfy AND matches your luggage!!! For you sewists, I'm wearing the Tate Top I made for fun at Roo's wedding along with these luscious linen Flint Pants!|
|This was our reward!!!! A lovely double rainbow and fun conversations about rainbows and ROYGBIV with other damp admirers!|
|Yummy dinner at El Canal. Yes, the Margarita pizza was mine and I ate every bite!!!|
|An all me-made kind of day! Vintage S6544 Pants, whose outer pocket was perfect for slipping your phone in and out of!, Jean Jacket B5616 and Grainline Studio Archer button-up!|
|We were greeted with pretty fall leaves...|
|...and mums that were celebrating with Roo and Jamie's wedding colors!|
|Remember when we thought Watergate was bad????|
|Remembering the fun of seeing these "creatures" with the kids years ago and wondering about a world filled with them ever so many years before that!!!!|
|A happy boy! Yummy gambas, tortilla and pulpo at Bodega Spanish Tapas and getting to speak Spanish with the Texas/Mexican proprietor!|
|Same pants, but you can see their amazing pocket a bit better. Paired with Grainline Studio's Linden sweatshirt and rtw sweater today. Feet a bit blistered and bunged up from walking so far in wet shoes. But nothing a few band aids couldn't fix.|
|B loves zoos. I have mixed feelings about them. However, the DC Zoo is very well laid out and park like. AND entrance is FREE as it is part of the Smithsonian.|
|My favorite menke!!!|
Our return walk home via a bike/running path along Rock Creek gave us a great view of these guys!
|Wood ducks never look quite real!!!|
|Delicious falafels and humus! So much that we had enough for breakfast! A little weird, but not bad with tea!!!|
Grateful for my Bentie and the beauty of rainbows! Off to Maryland tomorrow!!! - Travel chaotically!!! ~les