Thread by @BettinaRyll

It's Friday evening. And today is the day where I've been patient-involved one too many times. So all of you patient-at-the-heart-of-all-we-dos, this is for you 🧵

I got into patient advocacy because #Melanoma killed my husband in a horrific way. And the healthcare system overall, in particular the clinical trials that were his only option, only added to the insult.

He died barely 37. I was 35. Our daughters 4 and 6. The time between his diagnosis and his death- and the time after- were horrendous. Looking back, I'm not quite sure how I managed. But I DID manage.

Because you see that it is times like this that show you what you are really made of. You got no time for your personal hang-ups, your insecurities, your vanity, your ego. I've cried in more places than I care to remember

I've negotiated. I've begged. I've called in favours. I've downright lied. I've been told not to hope. I've been sat down by the palliative care team to consider what I did for him. And what for myself. I've closed my husbands' coffin- it's screws, not nails btw.

I also have a first class Medical degree. And a PhD in Biomedical Sciences. And years of research experience. So what *exactly* in all of this makes you think I'd be delighted to give you an emotional, fluffy waffy talk so you can feel good about your job?

And then, I'm obviously not representative. Horror can take endless forms, cancer and otherwise. I've been privileged to meet people who are just jaw-droppingly good at things I will never stand the slightest chance at

Negotiations? Data? Law? Management? Investment? Communication? IT? Organisation? Asking the REALLY tough questions? Philosophers? Design? I can tell you it ain't me....

The point is that this is a community of people with horrific experiences and who are challenged and have challenged themselves to the core, who at the same time have down-right expertise. I'm happy to bite for myself, but these people deserve ANYONE's respect.

So, to make this somewhat more tangible for the novices to this field, some case studies:

1. The WWJAPs- 'we want just a patient'. Under the pretence of inclusion 'we also listen to the uneducated patient' it has a deeply disturbing foundation, namely that you can only be a 'real' patient if you have no relevant expertise (that OMG could challenge the status quo)

WWJAPs sound like 'so tell us about your REAL experience (and some family photos pls). It will give a 'human' perspective. We will be deeply moved. Until the coffee break. At which you will leave- that rest is confidential, too technical anyway. Will help with staff motivation'

This is twitter, so artificially short- so pls just scatter some 'patientcentric' and 'thepatientatheheartofeverythingwedo's at random places over it.

2. The LPWS- Let's Pretend We're Systematics- an advanced form of neighbourhood watch in its best cliché (I grew up in the Ruhr area where it's basically people hanging over pillows out their windows watching what's going on in the street, not doing anything)

When it comes to patient involvement, that's writing yet another review of what people are doing in terms of patient involvement. While most importantly, NOT ENGAGING IN IT YOURSELF.

Pointers- assume a wistful tone 'the way of the future uhum', 'best practice sharing' is a MUST and in today's world it's critical to worry about social representativeness and inclusion-

but it is obviously totally inappropriate to call out that those patient involvement activities take place during working hours which not anyone can afford to loose and that e.g. the travel allowance only suffices for those living in the close posh neighbourhood.

3. The (PB)2SCSs - short for 'pretty bow on a pretty box still containing 💩'- which probably is one the most educative metaphors I've ever found 🤔 for pretend patient involvement in clinical trial design.

You know the type where they let patients waste their time on arguing whether green or yellow or Arial or Times would be better for the Informed Consent for a clinical trial? While the real discussions about trial designs are off-topic?? WONDER WHY

My dear colleague and friend @jangeissler happened to be passionate about this topic in his youth. And has produced some fantastic material on it- I suggest you cite him and move on to the stuff that matters.

I also recommend @eupatients for a solid education in drug R&D (it's a program modelled on a Master program for patient advocates interested in drug development)

The points to remember are that clinical trials are one of the most contentious while at the same time, most relevant fields of patient involvement with a lot of funding and vested interests at stake

As a patient/ patient advocate the MOST important question to ask yourself when asked to comment on a clinical trial is 'did they ask me for what I know? Or for what I do NOT know?'

If you look at a clinical trial and you don't really know the condition, the drugs that are tested or why they are tested- chances are very high that you are the guinea pig to see how that trial will *appear* to uneducated patients

The most important thing to realise as a patient or someone close to a patient is that there is your own personal experience, usually of phenomenally disastrous size, then, there is your ability to see others' disasters which might be different. And then, your techie brain

Nothing of what we do takes away the tragedy to ourselves and our loved ones. Still, there will be traits of our disasters that we share with others- and those that are very much us. And then, as my friend Pati said, we didn't get a brain amputation, did we.

So in my mind, one of the most essential things anyone of us in patient advocacy has to do in such a situation is disentangling the elements- what is me? what is typical for everyone here? And where is that brain that could make a difference RIGHT NOW?

Obviously wasn't done, was I. So to continue....

Clinical trial design is what got me into advocacy- and that started in 2021, when my husband needed the first Ph3. THAT randomisation is up on my personal list of horrors- with his Stage 4 diagnosis and his death.

So I've been in this space for 10 yrs now, I'm one of those always talking too much 🙄, so there's plenty of things out there that I've said on the topic, most of which I'm not embarrassed about. So here just some corner stones not to totally explode the thread

This I've written on why we have to change the way we run clinical trials. People aren't born to be sacrificed to our methods. nature.com/articles/s4157…

This is on where to most wisely invest your time in trial design for maximum impact, btw not only relevant for patient advocates

The important point to realise here is that actually, it isn't really about issues with listening to patients or anyone else for the matter- you're up against a major sunken cost fallacy.

I recommend reading @alialmossawi on faults in logical thinking, you'll find the entire collection in patient advocacy, in particular in clinical trial design

I haven't met a single person going 'I want to design a clinical trial that patients hate, that doesn't recruit, cost me a lot of money, makes my translational approach look like a total beginner project and will change nothing in the end'

But ONCE people have invested a lot of time and energy into a protocol and fallen in love with their own ideas, *try* telling them that patients will hate it, it won't recruit, that the translational approach is amateurish and it will cost money but not change anything....

I would recommend to portion your opinions wisely, maybe start with 'thank you very much for trying', acknowledging efforts is always good; also consider taking cover under the table. Better get used to being *very unpopular*

Over the years, I have softened my approach- at the beginning, I started showing calculations on how many years of life we lost to comparators we knew were inferior from the beginning- DTIC in #Melanoma gave plenty of that

Personally, I still think you shouldn't design trials in humans if you can't stomach the consequences of your designs. But it caused too much upset- I was told I was scaring the young oncologists 🙄🙄🙄

I also freely admit that it takes me A LOT OF PERSONAL CONTROL when people come to us...asking for help with trial recruitment...when we told them from the beginning their trial wouldn't recruit...and the design still stinks....

Overall, people really hate it when you point out the human cost of their clinical trial designs. It's a bit like our #MBC hating pink October, really. Trials are supposed to look shiny, patients grateful and p-values small.

And the only reasonable way out off this mess- you can obviously educate patients so they don't fall for stupid trials- don't forget TRIALS THAT DONT RECRUIT GET AMENDED OR CULLED but that is STILL valuable resources and above all, time, lost- and we don't have time in cancer.

So the ONLY good way out is to start as early as you can and to smarten up on the matter as much as you can. Being there before anyone has invested major time and effort and thinking about novel solutions is time much better invested- and way more pleasant, too.

Some pointers where things often go wrong in my experience: 1. weak questions 2. designs that are unattractive or downright unethical 3. weak translational research 4. the cheapest short-term

Though for me it falls under unethical, someone like @statsepi would probably add poor statistics but any sloppy experimental design that never stands a chance to deliver results is IMO unethical, be it insufficient powering, lack of quality controls etc

Oddly enough, these are all areas in which advocacy can do *a lot*. Good questions come from good observations and understanding context, spending some time thinking and discussing what really matters in our specific diseases won't hurt anyone

As a patient organisation, you want to have an opinion on what our community needs in terms of research. Volunteer it whenever and wherever you can. Listen to what your oncologists think is missing. Researchers. You might disagree but then, you might have missed something

There is a lot one *could* study. But much less one *should* study. We are part of the research ecosystem whether we like it or not- so better be part of the discussion and make it as constructive as possible.

2. Designs are critical. It's healthy to remember that trial designs aren't laws of nature, they are man-made. So they can and they do change. Trials have to work for the people on the trials (I don't believe in recruitment by desperation nor moral appeals to altruism)

and for the people who will use the trial data. While everyone should have a personal stance on whether it's ok to sacrifice cancer patients on trials or not- I object as I would not want to be the one sacrificed, this is a good book on the subject en.wikipedia.org/wiki/Skin_in_t… btw

It's also patients who suffer when treatments get stuck in regulatory or HTA agencies and it's particularly annoying when that's because of some obvious design fault in the trial. We've seen it now over and over- anticipating later needs and questions is GOOD trial design.

Classic one would be inappropriate hrQoL instruments. Missed the opportunity to test in early trials, used a readily available but insufficiently sensitive one in confirmatory trial, then stuck in HTAs who want to see more and more of this data....sigh.

3. Translational research. Often considered as bolted-on-afterthought-nothing-but-extra-cost. Huge missed opportunity for our community as a good translational program will allow you to dramatically improve the NEXT round of trials, potentially skipping a generation of them

The essence of a good translational program is 'studying the molecular underpinnings of a clinically relevant problem, with the fastest possible transition from the experimental (research) to the healthcare (validated) setting'

Means you need one who is good at spotting clinically relevant problems, one who is good at the basic Science behind it. And then, one how to translate it into something that actually benefits patients ('exploratory biomarkers' only produce papers, not patient benefit 🙄🙄🙄)

Means: combination of different expertise, a process management- you cannot just put a group of very different people together and expect they automagically manage themselves most effectively, especially not the *transitions*

Then, add supporting infrastructures like biobanks and technologies- imaging, liquid biopsies to the mix. And last but not least, the big data debate. And suddenly, there is A LOT where patient advocates can make a difference....

If you don't believe me, insufficient translation is a headache for many, including research funders (so advocates, make sure you sit on those grant committees) but if there's someone with real skin in the game, it's patients.....

So expertise in this area- what it takes, who has the expertise, some solid process management, ways to get it funded, plus some advocacy spirit to get people to keep their eyes on the prize: BETTER OUTCOMES FOR PATIENTS- is invaluable.

It's not for everyone however, so my advice would be to go looking for or build a network of those who really want to make a difference and are mature enough not to let their egos run the show, also, don't waste time with laggards.

The odd thing is that this requires a mix of very different skills, also those 'unusual' in the traditional research setting. And as cancer hits across all groups of society, you will be surprised what type of expertise you already have in your own networks....

So I guess you can look at 'patient involvement in clinical trials' and be reduced to the disaster of your life, get to choose yellow over green informed consents and upset people by telling them their trials aren't very smart

Or you find yourself a group of smart and driven people who care to make a REAL difference and make it your job to patchwork the different expertises, fill the gaps and mop up all outstanding jobs to create a system that works.

Have a guess which version I prefer 😎😎😎

4. 'Trial design by what you have, not what you should have'. While I'm all for pragmatism, settling for the wrong short-cuts big time. Using the 'worst possible comparator' might make the trial cheaper due to large effect size

but then violates equipoise, however much one tries to call it 'standard of care'. Hurts patients multiple times- bad comparator on trial, as it's often an outgoing SOC, it's outdated by the time the trial comes out, making the trial close to irrelevant by design

Also, if the trial is not attractive and recruitment slows, the moment the new SOC comes out, the trial is dead. Wasted resources and more importantly, patients exposed to something that never stood a chance to start with.

Similarly, no money for translational research= huge missed opportunity. If it means having to run another full trial lateron, it's simply another false economy- saving money today but spend much more later.....

For patient organisations wanting to become involved in trial design and those designers actually interested in making this as successful as possible I think the main lesson is that the REAL work has to happen before there is even a trial.

I know that some of my advocacy colleagues tend to get annoyed when they get invited somewhere and there just seems to be no clear idea what they are supposed to do there.

However uncomfortable and vague, I actually think these are the most important 'spaces' to create. You want all issues up in the air, people not very invested in any particular way yet, the opportunity to explore different options

If you then have a clear understanding of the issues of your patient community, you can move mountains (or rather: brains). And not so hard to do, we always seem to have a lot of good discussions at our conferences