A Clinical Trial Failed Patients

Something horrible happened – a clinical trial failed, causing one unexpected death and seriously injuring 5 people. And instead of dealing with a dysfunctional research system, “experts” are spouting off on their own. The few articles written to date focus on the drug (aka the money), not on what people want to know.

My Initial Thoughts

high wire climbing in the wood

ClinicalTrialsArena asked me to comment, due to my unique expertise that straddles the patient and research worlds. After researching the topic,* here are my concerns – most of which have not been discussed yet.

This poses a much larger question – why am I the one bringing these up?

Fact 1: Something really bad happened – the first 6 people to get “repeated higher doses” died or were seriously damaged. This is a clear sign of system failure (e.g. approval, protocol, procedures, formulation, PharmcoDynamics).

Fact 2: A phase 1 clinical trial means it is the first time a drug is studied this way in people. 127 people in the trial is far larger than classic phase 1, and most don’t have placebos. Isn’t this more like a phase 2, or the new-fangled phase 1-2 trial? If so, what happened to the rules?

Fact 3: The drug showed activity in laboratory dishes and animals first. We don’t know what mouse-realtesting was done, or for how long. How realistic are the animal models, and how closely do they relate to humans?

Fact 4: Existing articles stress the need for more ‘transparency’ to share the drug’s molecular structure. Patients want honesty first, which in this case may mean, who screwed up?

Fact 5: I’m a big believer (and trail blazer) in presenting trial results, but that’s when we have results. NOT during an ongoing, active clinical trial. Why aren’t we calling for the protocol to be publicly published immediately?

medical_1000006456-120613intFact 6: Healthy volunteers joined this trial after reading an ‘informed consent’ form about its procedures and risks, and they were paid well. Why isn’t the consent form (for every trial) publicly available once the trial is approved?

Fact 7: In the U.S., the Institutional Review Board (IRB) would be shut down and investigated before any new trials could be opened.

Fact 8: A thorough investigation on all parts of this system failure is obvious. This, too, should be open and as public as soon as possible, and at all times.

Fact 9: Risk is an inherent part of clinical trials because risk is part of everyday life. Even when rules are followed, bad things can still happen. Patients aren’t stupid, so there is no need to shut down other clinical trials.

A Setback for Other Clinical Trials?

Amazing we even have to ask this question, right? Of course it will!

Only other researchers may think their trial will be ok because, oh let’s see, because that trial was different – yes, that’s it! That trial (take your pick):

  •  was in a different disease
  •  was in a different country
  •  was run by a company I don’t know
  •  had a different study design
  •  was a horrible accident that would never happen to me
  •  add your own excuse

But patients won’t care about any of that. They’ll steer away from danger or discomfort. And let’s face it, anything called a “clinical trial” isn’t comforting. And as far as whether the rule were (or weren’t) followed – that doesn’t matter either. The rules in the case of a clinical trial include the protocol, of course.

I am firmly in the patient/participant camp. Some may call this a bias, but I consider it the only worthwhile endpoint. I know patients want better answers NOW, and I know people in research deal daily with regulations and hubris.

There was clearly a system failure here, and people needlessly paid too high a price. Let’s find out why and make the pieces work together so people won’t worry about needlessly putting their lives on the line.

* Online information (as of 1/21/16) about the French clinical trial from a Portuguese company is located on Facebook, at #clinicaltrials on Twitter, and is listed in articles from:

All content © 2016 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

Quality Diet Research Needed

Welcome to the controversial world of dietary recommendations. Seriously, what do you do when you hear opposing stories about fat, cholesterol, carbs, supplements, etc.? Probably the same thing the experts do – expound on your own opinions and go get a snack!

Debate from All Sides

Guidelines Key Showing Guidance Rules Or PolicyCriticism ignited over recent U.S. Dietary Guidelines (USDG), which diluted evidence that disagrees with long-held dogma from the nutrition establishment. A really good CardioBrief article from Larry Husten (reprinted in MedPage Today) explains. Bottomline – it’s time for nutrition research to set and use standards. Hopefully, they will implement them more effectively than some fields (but that’s another story).

“…it is time to transition from the current evidence-free zone to an era where dietary recommendations are based on the same quality evidence that we demand in other fields of medicine.”
Steve Nissen, Cleveland Clinic in Annals of Internal Medicine

One crucial point to consider is the difference between a true cause vs. a related factor (correlation) to a health problem. By the way, this Los Angeles Times article explains “correlation is not causation.” Unfortunately, the USDG did not take this into account, according to this criticism:

“…in the 2015 DGAC [Dietary Guidelines Advisory Committee] report, the distinction between correlation and causation is either ignored or dismissed.”
– Edward ArcherGregory Pavela, and Carl J. Lavie in Mayo Clinical Proceedings

So What?

If this was an esoteric debate between scholars, no one else would care. But we have to care. Guidelines impact millions of people whose health may get worse, as evidenced with increasing levels of obesity and diabetes when people replace fat and cholesterol-laden foods with sugar and carbs. Experts are also worried about trends in coronary heart disease, some cancers, and other diseases.

Why Diet is Hard to Study

breakfast_MJS16UtuAnother excellent article in Vox from Julia Belluz outlines 6 major reasons why it’s hard to study nutrition, according to 8 health researchers. Please read the article for details – here are the reasons:

  1. It’s not practical to run randomized trials for most big nutrition questions.
  2. Instead, nutrition researchers have to rely on observational studies — which are rife with uncertainty.
  3. Another difficulty: Many nutrition studies rely on (wildly imprecise) food surveys.
  4. More complications: People and food are diverse.
  5. Conflict of interest is a huge problem in nutrition research.
  6. Even with all those faults, nutrition science isn’t futile.

Where Does This Leave Us?

Today’s “precision medicine” promise (notice I didn’t say reality?) shows that bodies handle food, drugs, and other things differently. All of our guidelines need to reflect this. Research standards can also account for observational challenges and research bias. Conflicts of interest should also have major repercussions for abuse, such as losing research and/or medical privileges. These are just a few of the changes needed in this important field of research. Please voice your opinions whenever and wherever possible.

All content © 2016 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

Clinical Trial Patient Summaries Win!

Congratulations to the MRCT Center of Brigham and Women’s Hospital and Harvard and team for winning the 2015 Award for Excellence in Human Research Protection from the Health Improvement Institute! The winning project recommends ways to write public summaries after a clinical trial is over.

Why Is This Important?

  • People join clinical trials (research studies) so researchers can learn if new treatments, tests, procedures, or other things work better than what is now offered to patients.
  • People who join the trial are research participants, and contribute a great deal – sometimes their very lives.
  • Participants are told they’ll learn important things about the study, but they rarely receive a summary of what happened during the trial. Until now (hopefully).

Thanks, Europe!

The European Medical Agency (EMA) created a new rule that says ALL clinical trial sponsors must create a public summary within 1 year after a clinical trial is closed (6 months for trials with children). This rule scared sponsors (aka drug companies, government, and private funders), so the MRCT Center assembled a Return of Results (ROR) Working Group (WG) to help.

Why did it take a government regulation to make this happen, you might ask?
Oh, they must have been busy with things more important than telling people what happened (sigh).

What is the Return of Results (ROR) Project?

sign direction expect-result made in 2d softwareThe MRCT Center ROR project focuses on patient needs (for a change!), instead of just the research system. This means including principles about plain language, health literacy, and how to explain numbers (numeracy) – making sense of clinical trial results for normal people.

The ROR project includes:

  • A Guidance Document: how to set up a process to create patient summaries.
  • A Toolkit: with helpful templates, non-promotional language, and checklists.

We studied a few groups who actually create clinical trial result summaries, like CISCRP and the Alliance for Clinical Trial in Oncology (disclosure – I run the summary project there).

The Award

“The award program recognizes submissions that our judging panel determines have demonstrated excellence in promoting the well-being of human research participants.”

– Dr. Peter G. Goldschmidt, President and Founder of Health Improvement Institute

Quite a mouthful, but nice recognition! They agree the ROR Project puts patients first.

Thanks to All

Thank you

Thank you

As Co-Chair of the MRCT Center ROR Working Group, along with Laurie Myers from Merck, we thank all 53 team members (pp. 2-4) for creating ‘how to’ information for all clinical trial sponsors to create plain language study result summaries for real people. Thanks also to Barbara Bierer, Rebecca Li, and the MRCT staff. We’ll continue to update as new information becomes available.

A Plea to Sponsors

The tools exist, so let’s get started NOW! Don’t wait for the EMA ruling or for the U.S. Food & Drug Administration (FDA) to follow suit. Patients, trial participants and the PUBLIC want these NOW. And some of us can help. Really. Contact me!

After all, it’s the right thing to do AND you really need some goodwill, but that’s another story…

What YOU Can Do

Please ask for a public summary of any clinical trial you want to know about. You can find most trials listed at https://clinicaltrials.gov/. And ask them to stop calling them “lay” summaries (what does that really mean, anyway?).

More information on clinical trial result summaries is in this post.

All content © 2016 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

But, How Do I Get an eBook?

I recently found out I’m not the only one who feels inept about the eBook world. What a relief! The eBook world is exploding, so check it out if you haven’t already.

According to M LeMont,

“Over 70% of Internet users access the Internet via mobile devices instead of a PC” and “Less than 10% of mobile users have a Kindle.”

Confession – I didn’t know how to download eBooks until this year. And I just co-authored one!

If you don’t own an e-reader, you can still download and read eBooks on your smartphone, tablet, computer or web browser. All you need is an app – there are lots to choose from. Here are a few:

So what are you waiting for? Oh, and if you want a trial run, you can always download my eBookDCIS Dilemmas eBook - Press Releasecartoon-smiling-face_7Jwl-z_L

All content © 2016 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

A Plan for Real Research Improvements

Looks like 1,772 of us posted public comments about medical research informed consents to the NPRM docket! I realize this sounds obtuse, but bear with me through this post – please!

So, What’s the Big Deal?

The final regulation will affect millions of patients, researchers, institutions, and companies. These rules last changed in 1991. You know, before the internet existed for mere mortals. Just after my first cancer, while I was still a Silicon Valley computer executive. When Terminator 2 was new. Before my son was born. But I digress. Background on research informed consents is in this post.

Important Points for Patients

Unfortunately, informing patients about research has too often become a check box as CYA (cover your aspirations) for institutions. Big business. Instead of a straight-forward PROCESS that tells people what to expect so they can agree (consent) to take part in research (or not). Seems simple, right?

Rather than lament, my comments explain how systemic changes should happen. But don’t hold your breath. BTW, I had to write a preamble due to the 5000 character limit. That ticked me off (!), so I wrote this introduction:

“My individual comments are listed in the attached letter, although as founder of Patient Advocates In Research (PAIR), I have helped thousands of patient advocates partner with the research system for over 20 years (and am personally a survivor of multiple cancers).

Since you have received so many concerns from researchers and IRB members, it seems appropriate to add to the sparse patient perspective that appears in the NPRM public comments. Here are a few key points, in addition to my attached letter:

  • It is past time to embrace technology that can help deliver a modern approach to informed consent for trial participants, instead holding fast onto antiquated mindsets, procedures and reliance on paper forms.
  • This is too important to limit comments to 5000 characters, hence the attachment. I have participated in far too many informed consent committees to rely on an ‘executive summary’ approach to comprehensively address the NPRM.
  • Please eliminate the terms “human subject” and “research subject” from all federal regulations. My premise and recommendation is attached.
  • Informed consent is a process, and should be acknowledged as such in federal regulations. The form is a check box.
  • The NPRM, HIPAA, and any other related regulations should NOT be viewed in isolation, but rather WITH the rest of healthcare. Regulations should state that all agencies should work together in an adaptive infrastructure to ensure rules are kept up to date in our changing world.

Thank you for the opportunity to comment on the proposed changes to the Common Rule, which is of utmost importance in protecting research participants (i.e. people) while fostering research. In this historic shift to modernize the Common Rule, the NPRM should create an adaptive infrastructure that allows for evolving science while supporting responsible participant partnership, choice, and engagement. Please view my comments in the attached letter as a complete package.”

The Whole Letter

Pages from NPRM public comments 1-6-16PLEASE read the details in this pdf. It’s not long, and posits a new adaptive approach to create an open, welcoming research system. We can actually push this forward with your help!

So, What’s Next?

You can see the 1,772 comments here – if you know the Comment Tracking Number (mine is 1k0-8n8m-6xee), you don’t have to look through all of them.

I have no idea how the comments will be used, but they promise to read and consider them. The research community has waited for years to get changes to the Common Rule. No one knows when the final rule will take effect, but it’s a safe bet it won’t be before 2018.

Please join the discussion about making research accessible and open – make it REAL for PEOPLE!

All content © 2016 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.