What's all the Buzz about Convalescent Plasma?

Vaccine development is not the only effort science is racing to develop and evaluate as part of our toolkit against COVID19.

Four former FDA Commissioner's have collaborated on this piece highlighting the latest on the study of convalescent plasma: https://www.washingtonpost.com/opinions/2020/08/03/4-former-fda-commissioners-blood-plasma-might-be-covid-19-treatment-we-need/?utm_content=buffer634f9&utm_medium=social&utm_source=twitter

The basis behind convalescent plasma is to use the defense system of antibodies from a person who has recovered from COVID19 to boost the immune response of a newly infected person.

If you have recovered from COVID19, consider donating plasma: https://thefightisinus.org/en-us#home

Donated plasma may be used for 2 different powerful routes:

1) Direct transfusion to a patient critically ill with COVID19

2) Development of plasma derived therapy

Excellent graphic detailing these 2 routes here: https://thefightisinus.org/images/TwoPaths.pdf

The federal government’s ACTIV program, also part of Operation Warp Speed, is standing up trials of promising treatments, including convalescent plasma and synthetic antibodies that work through mechanisms similar to plasma to neutralize the virus. For more information on the details of COVID19 trials: https://www.nih.gov/research-training/medical-research-initiatives/activ

Changing the Paradigm of Patient-Centricity

From a disappointed post on LinkedIN came a rich conversation and call-to-action for further discussion and actionable change. I’m grateful for the opportunity to now collaborate in a panel discussion on clinical trials in a COVID19 world.

As an advocate living in a COVID19 hotspot in northern NJ, it has been devastating to watch people desperately trying to connect with clinical trials during a pandemic, both for COVID19 trials as well as for various cancer diagnoses.

This has to stop. We must dream bigger.

Grateful for colleagues and friends, like Ritesh PatelJen HoronjeffKelly McKeeCraig Lipset, and Olivier Chateau who share my frustrations and jump at the chance to go beyond words and move to actionable change.

Join us on June 11th at 11 am EST as we get to the crux of clinical trials in a COVID19 world & hear what I believe is the new model we should be striving for.

[HINT: it's not patient-centricity]

Like a Sitting Duck

A recent publication in JAMA, Optimizing the Trade-off Between Learning and Doing in a Pandemic left a great void from the patient and carepartner perspective.

I'm disappointed to see that, once again, patients & their carepartners are NOT included in the potential solutions to enrich BOTH learning & doing while in a pandemic.

This is one of the biggest failures of the clinical trial landscape, COVID-19 or not.

  • What if we had a pandemic clinical trial consent process?

  • What if people could be informed of trial options ahead of time and proactively provide consent to clinical trials in anticipation of being diagnosed with COVID19?

  • Why can't I as a patient proactively consent to participate in a clinical trial for COVID19, as a just in case, especially while I'm literally sheltering at home in a COVID19 hotspot like a sitting duck?

We have advance directives for end-of-life care planning. Why not advance consent directives for potential clinical trial participation?

Just like the taboo about death and end-of-life care planning, talking about clinical trials is always too early, until it's too late.

Here's the article: https://ja.ma/3e72XJJ

Pharma's 50 Shades of Gray: Including Patients in the Clinical Trial Life Cycle

“Is there a form I could fill out to provide my feedback?”

The silence in the room was deafening.

I exhaled with a furrowed brow, feeling extremely disappointed, wanting to stand up and apologize on behalf of the entire room that was seated so quietly. Apologize for the practices, procedures, and ideologies that had failed this woman panelist on stage, and so many others. Apologize on behalf of an industry that is advancing on so many levels, yet dropping the ball in too many priceless ways.

“Is there a form I could fill out to provide my feedback?”.

This simple question came from a vibrant young woman who just delivered a powerful narrative that brought a quiet room to a roar with the applause of a standing ovation.  This young woman detailed her harrowing patient experience of dying of advanced cancer to a tremendous success story reveling in the miraculous power of personalized medicine. She is years post the clinical trial that saved her life.

“Is there a form I could fill out to provide my feedback?”.

If she hadn’t stood at the podium and told us her story, no one would’ve known the horrors she witnessed, felt, experienced, or thought. If she hadn’t stood on the stage and articulated her story, no one would have known about her difficulties of finding the trial that saved her life. Without her story, no one would’ve heard her suggestions for improvement. If she just sat in her seat like every other member of the audience, no one would’ve known how scary, how exhausting, and how painful her journey was. Thank goodness she was invited to share her story! Otherwise, she’d just be another anonymous clinical trial endpoint successfully met.

It’s gravely concerning that after participating in a successful trial, no one invited her to help improve the process. If an educated, well-spoken, personable individual with a miraculous response to a cutting-edge therapy isn’t included in the enhancement, refinement, and co-design of clinical trials, who will be?

It’s common to hear from patients that they are not asked for their insights during or after participation in clinical trials. There is an aura of reverence surrounding people who have participated in trials. These individuals have made a profound sacrifice and leap of faith. Trial participants have agreed to introduce a foreign substance, a hypothesis, into their body, realizing that this unknown may save their life, end it, or run the gamut of all of the possibilities in between.

Imagine being diagnosed with terminal cancer, being sent home to die. Shattered. In physical, mental, and spiritual pain. Would you risk trusting an unknown therapy and introducing it into your frail, already dying body? Could you picture yourself taking an experimental agent and hoping for the best? How many of us are truly brave enough to put our trust and fate into the hands of science? Wouldn’t you agree that these experiences are profound, rare, and worth their weight in gold to thoroughly comprehend?

There are over 21,000 clinical trials listed in clinicaltrials.gov as recruiting in the US.  Were these trials designed to be tailored to the lives of the people living with a diagnosis and inclusive of all lives with a diagnosis? It depends on whether the expertise of patients and carepartners were included throughout the continuum of the clinical trial life cycle.

Over the last year, it’s been my personal curiosity to ask members of pharma if their company includes patients in the clinical trial life cycle. When I broach the subject, there is a broad spectrum of reactions, the majority of which are accompanied by clear discomfort, agitation, defensiveness, dismay, and confusion. These responses all fall into an ambiguous gray area. Here are 50 answers I have received in response to the question: Does your company include patients’ expertise and insights in the clinical trial life cycle, from study design planning, during trial implementation, after trial closeout, and post-launch of product?

1.     There are compliance issues.

2.     There are regulatory hurdles.

3.     What business incentive is there to do that?

4.     Patients don’t know anything about clinical trial design, management, or operations.

5.     We don’t have a budget for that!

6.     The FDA doesn’t require patient feedback or insights in the clinical trial process for drug approval.

7.     (Look of confusion)

8.     Our company is patient-centered. We don’t need patient insights.

9.     We don’t have the staffing to do that.

10. Pharma doesn’t traditionally speak with patients.

11. Our stringent timelines cannot accommodate this.

12. Where would we find patients to participate?

13. (eyes narrowing) Are you one of those patient activists?

14. Patients aren’t well spoken.

15. Patients aren’t professional enough to participate in these conversations

16. Our legal team would go into cardiac arrest.

17. We do not have the technology in place to do this.

18. It sounds like a great idea but upper management would never approve.

19. Our marketing team is working on a campaign.

20. We only work with non-profits.

21. It’s on the backburner for this fiscal year.

22. This is a conflict of interest.

23. We’re one of the top biopharmaceutical companies in the industry. We know what we are doing.

24. Do you know how much it costs to execute a clinical trial?

25. (eye roll)

26. Our clinical operations team runs like a well-oiled machine.

27. Do you have any references or data to support the benefit of including patients in clinical trial design?

28. Patients are unreliable and volatile.

29. That’s a waste of time.

30. Working with patients is a pain in the @ss.

31. How could pharma work with patients? They don’t trust us!

32. Sounds great in an ideal world, but we have pressing deadlines to meet.

33. Patients have their own agenda and won’t collaborate.

34. We can’t base our clinical trials on patient complaints.

35. Our company runs successful trials and gets approvals without patients involved in the process.

36. That’s another trend that will phase out soon.

37. Whose responsibility would that even fall under at our company?

38. We are watching to see how other companies are doing it.

39. Those tactics are for companies that can afford the “bells and whistles”.

40. We tried. It didn’t work.

41. We are too small of a company to implement this.

42. We don’t need more paperwork.

43. What is the return on investment?

44. We’ll talk to patients but we can’t pay them.

45. We are too big of a company, with locations all over the world. How could we coordinate this?

46. We are so overwhelmed, we can’t take on another initiative.

47. Is there a standard operating procedure for implementing this?

48. What happens if they all start talking about the adverse events of their treatments?

49. How can we trust patients?

50. Our investors don’t care about patient-centered practices and co-design. They want drugs going to market.

Pharma’s 50 shades of gray does not run industry wide. There are pioneers who are committed to changing the status quo, actively working with patients and including them on many fronts. It is evident that these trailblazers are excited by their partnerships with patients. They speak loudly and proudly about their patient-centered initiatives, with an enthusiasm that is invigorating and resounding. They acknowledge that this isn’t a just a nice gesture or outreach program. Partnering with patients is solid business sense.  Collaborating with patients bridges silos, brings meaning to daily work, and creates unique opportunities for experiential learning.

It is important to note that those within pharma who collaborate with patients are more open to leveraging technology and machine learning, discussing mobile health, digital platforms, and telehealth, exploring benefits of utilizing blockchain, as well as recognizing the importance of patient-reported outcomes. Coincidental? Absolutely not.  There is unprecedented value and power in including patients in optimizing the drug lifecycle. Augmenting trials to patients’ values, preferences, and needs is a solid win on all fronts. Do not mistake this as another passing trend!

Is your company somewhere in the 50 shades of gray? What is holding you back? Is your company a pioneer in being authentically patients first and collaborating with patients? How can early adopters share best practices to eliminate every single one of these 50 gray areas so as to collectively move the industry forward to being truly patients first?

The Glaring Omission in Kymriah Drug Approval Press Releases

Novartis received F.D.A. approval for Kymriah (tisagenlecleucel), as the first CAR-T gene therapy approved in the US for pediatric and young adult patients with relapsed B-cell acute lymphoblastic leukemia (ALL).  Kymriah is being hailed as a paradigm and life changing therapy. Clinical studies have shown that within 3 months of treatment, patients achieved overall remission rates of 83%, survival of at least six months by 89%, with a 79% chance of survival of at least a year. These are tremendous clinical feats for patients with limited to no treatment options. The price for the single treatment therapy is $475,000. Novartis is working with the Centers for Medicaid and Medicare Services where patients will only be responsible for payment if they respond after 1 month of treatment. The company has also reported it would provide assistance to those without insurance and the underinsured.

The CEO of Novartis Oncology, Bruno Strigini, said, “We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program(1). The majority of press releases (2-14) reporting the approval all had one glaring omission. Not a single press release formally recognized the importance of the patients that volunteered to participate in the trials. Not a single one expressed gratitude for the dedication of the care partners that committed their time to the success of these trials. Many trials fail to recruit and retain enough patients (15), leading to early termination, delays, or inadequate data for statistical reporting. Considering Kymriah is a treatment geared to a very specific subset population of ALL, it is incredible that these trials were able to accrue and retain the necessary numbers of patients to generate statistically significant findings.  Clinical trial participation requires dedication, sacrifice, and an uncanny belief in the unknown.  Imagine the degree of mental, physical, emotional, and spiritual duress a parent or guardian experiences in deciding whether their child, who is in the throes of a terminal cancer diagnosis, should participate in a clinical trial.  In the cases of pediatric and young adults patients, one parent, if not both, often need to significantly decrease the number of hours they may work, take an unpaid leave of absence, or leave their job permanently to assume the role of care partner for the patient so as to follow trial protocol. One can only imagine the impact on a single parent household. While there were clearly never seen before successes, with many precious lives saved, it wasn’t a miraculous ending for ever patient that was treated.  There are also life-threatening sides that come with treatment. Even the success stories may have had many dark moments along the way.

At a time when the healthcare industry is exploring and investing in initiatives to promote patient-centricity, it is important to acknowledge all stakeholders involved in successes such as these.  While Kymriah is undoubtedly a groundbreaking approval representative of the epitome of exceptional science, dedication, and innovation, let’s not forget to credit the patients and care partners who made this innovation and approval a reality as well. While researchers may have dedicated years of their careers developing the basic science and pharma may have invested close to a billion dollars to bring this living drug to market, the most invaluable part of Kymriah’s product lifecycle was patients’ volunteering their lives to the development of what’s being hailed as historic breakthrough science.

Resources:

1.     Novartis. (2017, Aug 30). Novartis received first ever FDA approval for a CAR-T cell therapy, Kymriah (tisagenlecleucel, CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice [Press Release]. Retrieved from https://novartis.gcs-web.com/novartis-receives-fda-approval-for-KymriahTM

2.     Berkrot, B. (2017, Aug 30). Novartis gene therapy approval signals new cancer treatment era [Press Release]. Retrieved from http://in.reuters.com/article/us-novartis-fda-idINKCN1BA1ZY

3.     Cortez, M., Edney, A., &Paton, J. (2017, Aug 30). Breakthrough cancer therapy for dire cases gets FDA approval [Press Release]. Retrieved from https://www.bloomberg.com/news/articles/2017-08-30/breakthrough-genetic-treatment-for-dire-cancers-approved-by-fda

4.     The Food and Drug Administration. (2017, Aug 30). FDA approval brings first gene therapy to the United States [Press Release]. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm

5.     Garde, D. (2017, Aug 30). Pioneering cancer drug, just approved, to cost $475,000- and analysts say it’s a bargain. [Press Release]. Retrieved from https://www.statnews.com/2017/08/30/novartis-car-t-cancer-approved/

6.     Glenza, J. (2017, Aug 30). US approves first cancer drug to use patient’s own cells- with a $475,000 price tag [Press Release]. Retrieved from https://www.theguardian.com/us-news/2017/aug/30/cancer-drug-kymriah-leukemia-novartis

7.     Grady, D. (2017, Aug 30). FDA approves first gene-altering leukemia treatment, costing $475,000 [Press Release]. Retrieved from https://www.nytimes.com/2017/08/30/health/gene-therapy-cancer.html?mcubz=3

8.     Herper, M. (2017, Aug 30). Novartis CEO’s dilemma: Is $475,000 too much for a leukemia breakthrough? Or is it not enough? [Press Release]. Retrieved from https://www.forbes.com/sites/matthewherper/2017/08/30/novartis-ceos-dilemma-is-475000-too-much-for-a-leukemia-breakthrough-or-is-it-not-enough/#772e4a77556e

9.     Nedleman, M. (2017, Aug 30). FDA announces first US gene therapy approval for cancer treatment [Press Release]. Retrieved from http://www.cnn.com/2017/08/30/health/fda-first-gene-therapy-leukemia/index.html

10. NPR. (2017, Aug 30). FDA approves first gene therapy for leukemia [Press Release]. Retrieved from http://www.npr.org/sections/health-shots/2017/08/30/547293551/fda-approves-first-gene-therapy-treatment-for-cancer

11. Ramsey, L. (2017, Aug 30). A medical breakthrough that hacks genes to fight cancer just got approved, and it’s the beginning ‘of a big new field of medicine’ [Press Release]. Retrieved from http://www.businessinsider.com/why-the-fda-approved-kymriah-a-car-t-cell-therapy-to-treat-cancer-2017-8

12. Scotti, A. (2017, Aug 31). New cancer drug’s ‘astronomical price’ only affordable for the 1% [Press Release]. Retrieved from http://www.nydailynews.com/life-style/health/new-cancer-drug-astronomical-price-affordable-1-article-1.3458071

13. Smith, M., Goodman, B. (2017, Aug 30). FDA approves first-of-its kind cancer treatment [Press Release]. Retrieved from http://www.webmd.com/cancer/news/20170830/fda-approves-breakthrough-cancer-treatment

14. Univeristy of Pennsylvania. (2017, Aug 30). FDA approves personalized cellular therapy for advanced leukemia developed by University of Pennsylvania and Children’s Hospital of Philadelphia Retrieved from https://www.pennmedicine.org/news/news-releases/2017/august/fda-approves-personalized-cellular-therapy-for-advanced-leukemia

15. Kolata, G. (2017, Aug 30).  A cancer conundrum: Too many drug trials, too few patients [Press Release]. Retrieved from https://www.nytimes.com/2017/08/12/health/cancer-drug-trials-encounter-a-problem-too-few-patients.html?mcubz=3