Bess, what the PI told you about biopharma companies: "...but we have to follow their rules. They don’t listen to the doctors" is only partially true. I am in the drug development space for over 20 years. The study teams I worked with during those years always run the study protocol by a trusted and experienced circle of prospective PIs, lobbied for a vague eligibility language to allow borderline-cases into the study, and offered support of clinical operations and medical monitors to resolve resolvable issues with patient eligibility and enrollment. The rules that we all - sponsors and study sites - must follow are the rules that regulatory and health ethic authorities established, described in ICH-GCP Guidelines, FDA Act, 21CFR50, 21CFR312, and in OHRP among other protective policies. Those laws, guidelines and policies are not to be breached or ignored for any reason. The sponsor submits the study protocol for approval to FDA and to Ethic Boards. Their approval means that the study is safe and sound to conduct in compliance with the protocol, no exceptions to the rule.
A drug study is a scientific trial that should be able to answer a question in a scientific way. That is why the eligibility criteria are narrow, to make the research subject population as homogenous as possible to make confident decisions based on the clinical data. Fraudulent data creation is a crime.
Lately, there is a workstream to investigate the introduction of clinical trials resembling to real-life scenarios like Jake's. Unfortunately, closer controlled studies in early phase development are absolutely necessary, but in late phase those studies would provide useful information about efficacy in real-world scenarios.
The role of the microbiome is very real, and fecal transplant treatment is the least invasive to the body systems, does not seem to harm the abundantly complex system.
Bess, I'm so sorry about what's happening to you. Let me explain why the rules need to be followed. Clinical trials are by their nature dangerous and experimental. And the FDA allow companies to conduct trials under very circumscribed conditions, in order to protect patient safety and rights. So the companies are not allowed to stray from what was agreed.
Good protocolmanship would write into the protocol enough leeway so that edge cases can be determined by the clinician, and if that leeway is written in, then there can be discretion for the clinician. Alternatively, leeway or procedures for exceptions to be granted by the medical director at the company can be written in. But there are folks who are good at writing protocols and there are those who are just OK at it.
Also, things that don't make sense for the treating clinician may be due to something only the pharma physician knows. And there are sometimes things in the protocol that don't make sense to the treating physician or even to the pharma physician - but the FDA, by virtue of their access to proprietary data across all trials, knows and mandates.
Given the reproducibility crisis and the intense financial and career pressure for these treatments to show results is any of this complexity intended to combat fraud?
I was in the clinical trials space for 30 years - I'm now consulting with a company who wants to attack these problems head on. Bess, your article is spot on and needs to be told. I've forwarded the link to a couple of CEOs in my network as well as some board members. We should be ashamed - I know I am. Prayers to your brother and family.
Could you share the name of the company you are consulting for? I work in the clinical trials space but have been affected by a lay off recently and would love to know where there may be opportunities to help tackle these infuriating problems.
Thanks for sharing this. I fall into bucket 2 (interested in structural improvements; I'm a state lobbyist and like helping on side projects like this). Would a helpful step be a searchable database like the NIH Clinical Trials for all trials occurring in all hospitals in a particular state (something a state legislature could require)? Or would a broader database based on the same schema of ClinicalTrials.gov that any willing Pharma sponsor or hospital with authority choose to participate in also be helpful?
This is fucking insane. The whole thing. It’s so infuriating. Searching for people to blame, it’s not people but the systems in place. If the primary motivation for medical progress is money, what are we even doing as a society?
3,000 people died in Pearl Harbor and we went to war, launched the Manhattan Project. 1.6m people per year are affected by cancer, but instead of throwing all available resources into it, we allow capitalists to call the shots?
It sure as fuck seems as though the pharmaceutical industry is more interested in keeping people sick than making them better, in the name of making more money. Where does 50% of my income go to? We are the richest country in the history of the world, and stories like this make us look like the foolish fucking chimpanzees that we are.
You are right Sam, it is insane. The reason is that the industry has to safeguard everything, because there are many that wants to cause harm. Safeguarding activities are equally expensive as the research itself. And it is sure, while fuck is not so much.
About 50 years ago 80% of medical research was funded by governments, these days 80% by the biopharma industry. The industry pays millions to hospitals and other research sites, there are fees to do everything, millions in fees to the government (FDA) to review the study results, and so on. Clinical research takes a lot of time, including waiting for regulatory authorities, research ethics boards and research sites to complete their reviews and deliver the results of their reviews.
Medical research is very expensive and time consuming. Montecuccoli, an Italian diplomat and military theorist in the 17th century said "You need three things to fight a war, money, money and money." The very same is true in novel drug discovery and development. I'd rather spend that money on scientific discoveries than fighting wars. And that is even surer than fuck.
Bess, what the PI told you about biopharma companies: "...but we have to follow their rules. They don’t listen to the doctors" is only partially true. I am in the drug development space for over 20 years. The study teams I worked with during those years always run the study protocol by a trusted and experienced circle of prospective PIs, lobbied for a vague eligibility language to allow borderline-cases into the study, and offered support of clinical operations and medical monitors to resolve resolvable issues with patient eligibility and enrollment. The rules that we all - sponsors and study sites - must follow are the rules that regulatory and health ethic authorities established, described in ICH-GCP Guidelines, FDA Act, 21CFR50, 21CFR312, and in OHRP among other protective policies. Those laws, guidelines and policies are not to be breached or ignored for any reason. The sponsor submits the study protocol for approval to FDA and to Ethic Boards. Their approval means that the study is safe and sound to conduct in compliance with the protocol, no exceptions to the rule.
A drug study is a scientific trial that should be able to answer a question in a scientific way. That is why the eligibility criteria are narrow, to make the research subject population as homogenous as possible to make confident decisions based on the clinical data. Fraudulent data creation is a crime.
Lately, there is a workstream to investigate the introduction of clinical trials resembling to real-life scenarios like Jake's. Unfortunately, closer controlled studies in early phase development are absolutely necessary, but in late phase those studies would provide useful information about efficacy in real-world scenarios.
The role of the microbiome is very real, and fecal transplant treatment is the least invasive to the body systems, does not seem to harm the abundantly complex system.
My thoughts and best wishes to Jake.
Bess, I'm so sorry about what's happening to you. Let me explain why the rules need to be followed. Clinical trials are by their nature dangerous and experimental. And the FDA allow companies to conduct trials under very circumscribed conditions, in order to protect patient safety and rights. So the companies are not allowed to stray from what was agreed.
Good protocolmanship would write into the protocol enough leeway so that edge cases can be determined by the clinician, and if that leeway is written in, then there can be discretion for the clinician. Alternatively, leeway or procedures for exceptions to be granted by the medical director at the company can be written in. But there are folks who are good at writing protocols and there are those who are just OK at it.
Also, things that don't make sense for the treating clinician may be due to something only the pharma physician knows. And there are sometimes things in the protocol that don't make sense to the treating physician or even to the pharma physician - but the FDA, by virtue of their access to proprietary data across all trials, knows and mandates.
Given the reproducibility crisis and the intense financial and career pressure for these treatments to show results is any of this complexity intended to combat fraud?
As an example:
https://www.cbsnews.com/news/deception-at-duke-fraud-in-cancer-care/
I was in the clinical trials space for 30 years - I'm now consulting with a company who wants to attack these problems head on. Bess, your article is spot on and needs to be told. I've forwarded the link to a couple of CEOs in my network as well as some board members. We should be ashamed - I know I am. Prayers to your brother and family.
Could you share the name of the company you are consulting for? I work in the clinical trials space but have been affected by a lay off recently and would love to know where there may be opportunities to help tackle these infuriating problems.
Catherine, please email me at charlene.l.dark@gmail.com
Charlene- feel free to reach out at DRBStillman@gmail.com especially if there’s any way I can help
Thanks for sharing this. I fall into bucket 2 (interested in structural improvements; I'm a state lobbyist and like helping on side projects like this). Would a helpful step be a searchable database like the NIH Clinical Trials for all trials occurring in all hospitals in a particular state (something a state legislature could require)? Or would a broader database based on the same schema of ClinicalTrials.gov that any willing Pharma sponsor or hospital with authority choose to participate in also be helpful?
Dan- would love to talk more about this with you! Can you shoot me at email at DrBStillman@gmail ?
I’m in the industry (not helpfully positioned, alas) and I have tears in my eyes rn. Incredibly important piece.
This is fucking insane. The whole thing. It’s so infuriating. Searching for people to blame, it’s not people but the systems in place. If the primary motivation for medical progress is money, what are we even doing as a society?
3,000 people died in Pearl Harbor and we went to war, launched the Manhattan Project. 1.6m people per year are affected by cancer, but instead of throwing all available resources into it, we allow capitalists to call the shots?
It sure as fuck seems as though the pharmaceutical industry is more interested in keeping people sick than making them better, in the name of making more money. Where does 50% of my income go to? We are the richest country in the history of the world, and stories like this make us look like the foolish fucking chimpanzees that we are.
You are right Sam, it is insane. The reason is that the industry has to safeguard everything, because there are many that wants to cause harm. Safeguarding activities are equally expensive as the research itself. And it is sure, while fuck is not so much.
About 50 years ago 80% of medical research was funded by governments, these days 80% by the biopharma industry. The industry pays millions to hospitals and other research sites, there are fees to do everything, millions in fees to the government (FDA) to review the study results, and so on. Clinical research takes a lot of time, including waiting for regulatory authorities, research ethics boards and research sites to complete their reviews and deliver the results of their reviews.
Medical research is very expensive and time consuming. Montecuccoli, an Italian diplomat and military theorist in the 17th century said "You need three things to fight a war, money, money and money." The very same is true in novel drug discovery and development. I'd rather spend that money on scientific discoveries than fighting wars. And that is even surer than fuck.