Clinical Trial Phases

Buckwirth

Clinical Trial Phase Purpose

A lot of posting of clinical trials lately, but do you know what each phase is about?

In a phase one trial they are looking for safety and dosage. (If the drug is not safe, or if the proper dosage cannot be determined, no phase two)

In a phase two trial the trial size is increased, with a goal to determine efficacy and further evaluate safety. (not effective, or causes more harm than good, no phase three)

In a phase three trial it goes to an even larger group, monitoring efficacy and side effects, and compare it to treatments already in use. If it does not perform better than current treatments, with the same or fewer side effects, it does not go to market. If it does prove to be a useful drug in phase three, approval is imminent and the drug goes to market for its designed purpose

Phase four trials follow the drug after it has gone to market, among diverse populations, and monitors for additional side effects from long term use. (turns out long term use causes heart failure, drug gets pulled or usage is modified, Celebrex is a good example)

Hopefully this is helpful. Next post will be about Mega Dose Chemotherapy, and the danger of reading too much into one trial...

Blake

Buckwirth

Mega Dose Chemotherapy
It was the late '80's and Aids was in full swing. Groups like ACT UP wanted a cure, and they felt they did not have time to wait for it. Political pressure mounted to make drugs that were in clinical trials available to those who had the disease now. After all, if it had made it to a stage two, or stage three trial, it was only a matter of time before it would be approved anyway.

There was another group that felt the same way: cancer patients. The new treatment of the moment: Mega Dose Chemotherapy for Breast Cancer.

We all know the chemicals in chemotherapy are toxic, and they kill healthy cells with the cancerous ones. But what sets the limit for how much chemotherapy we can stand? Bone marrow. Chemo in too high a dose kills the marrow, and in so doing, kills the patient.

In the early part of the 80's some enterprising researchers figured if they could drive to that edge, killing all the marrow, would they not kill the cancer too? Was there a way to bring the patient back from that terrible brink?

There was. Bone marrow transplantation. Harvest healthy marrow from the patient prior to treatment, then transplant it back before they are killed by some minor infection.

It was so obvious, and in a South African trial Werner Bezwoda cured 60% of his patients!

But the trials in America were not going so well. No matter, the treatment worked, it was proven. Clinics offering the treatment began popping up (including Norris Cancer Center, one of my hospitals). In 1992 Bezwoda claimed the dose limiting barrier had been overcome.

In 1993 Health Net lost an $89 million dollar lawsuit for disallowing the treatment to a Temecula school teacher. Eventually, seven states required insurers to pay for this treatment.

By the late '90's Mega Dose Chemotherapy for BC was a $4 billion dollar industry.

In the last decade of the century, forty thousand women underwent this procedure.

But the trials in America were not getting Bezwoda's amazing results. In fact, many of the patients were dying of the complications and side effects, including new, untreatable cancers in 10% to 15% of the patients, and many, if not most, had relapses within a year.

Someone must be doing something wrong. Bezwoda was now getting a 90% success rate in Johannesburg, so a retinue of American Oncologists requested permission to visit with him in South Africa. Perhaps there was some key in his procedure that would unlock the potential for everyone else.

When they arrived they asked for the study records all of the control data had been lost. Then when examining the treatment data key things seemed to be missing. No trial release forms, jumbled names, poor follow-up, and at least one man named as a BC patient.

Bezwoda had faked everything.

Note that at no time did the FDA, or any other government regulatory body ever say this treatment was anything but experimental, though they did bow to political pressure to use the Compassionate Use clause to allow the procedure to be used outside of a study.

Note also that the discovery of fraud came from the world of science, from those who did the research and ran the trials, those who could not duplicate Bezwoda's results.

Credit to:

Siddhartha Mukherjee for The Emperor of All Maladies
Journal of American Oncology

John23

Buckwirth said:

Mega Dose Chemotherapy
It was the late '80's and Aids was in full swing. Groups like ACT UP wanted a cure, and they felt they did not have time to wait for it. Political pressure mounted to make drugs that were in clinical trials available to those who had the disease now. After all, if it had made it to a stage two, or stage three trial, it was only a matter of time before it would be approved anyway.

There was another group that felt the same way: cancer patients. The new treatment of the moment: Mega Dose Chemotherapy for Breast Cancer.

We all know the chemicals in chemotherapy are toxic, and they kill healthy cells with the cancerous ones. But what sets the limit for how much chemotherapy we can stand? Bone marrow. Chemo in too high a dose kills the marrow, and in so doing, kills the patient.

In the early part of the 80's some enterprising researchers figured if they could drive to that edge, killing all the marrow, would they not kill the cancer too? Was there a way to bring the patient back from that terrible brink?

There was. Bone marrow transplantation. Harvest healthy marrow from the patient prior to treatment, then transplant it back before they are killed by some minor infection.

It was so obvious, and in a South African trial Werner Bezwoda cured 60% of his patients!

But the trials in America were not going so well. No matter, the treatment worked, it was proven. Clinics offering the treatment began popping up (including Norris Cancer Center, one of my hospitals). In 1992 Bezwoda claimed the dose limiting barrier had been overcome.

In 1993 Health Net lost an $89 million dollar lawsuit for disallowing the treatment to a Temecula school teacher. Eventually, seven states required insurers to pay for this treatment.

By the late '90's Mega Dose Chemotherapy for BC was a $4 billion dollar industry.

In the last decade of the century, forty thousand women underwent this procedure.

But the trials in America were not getting Bezwoda's amazing results. In fact, many of the patients were dying of the complications and side effects, including new, untreatable cancers in 10% to 15% of the patients, and many, if not most, had relapses within a year.

Someone must be doing something wrong. Bezwoda was now getting a 90% success rate in Johannesburg, so a retinue of American Oncologists requested permission to visit with him in South Africa. Perhaps there was some key in his procedure that would unlock the potential for everyone else.

When they arrived they asked for the study records all of the control data had been lost. Then when examining the treatment data key things seemed to be missing. No trial release forms, jumbled names, poor follow-up, and at least one man named as a BC patient.

Bezwoda had faked everything.

Note that at no time did the FDA, or any other government regulatory body ever say this treatment was anything but experimental, though they did bow to political pressure to use the Compassionate Use clause to allow the procedure to be used outside of a study.

Note also that the discovery of fraud came from the world of science, from those who did the research and ran the trials, those who could not duplicate Bezwoda's results.

Credit to:

Siddhartha Mukherjee for The Emperor of All Maladies
Journal of American Oncology

Blake -

Re:
"Note also that the discovery of fraud came from the world of
science, from those who did the research and ran the trials,
those who could not duplicate Bezwoda's results"

And who paid for that "research", pray tell?

Good health to you,

John

Buckwirth

John23 said:

Blake -

Re:
"Note also that the discovery of fraud came from the world of
science, from those who did the research and ran the trials,
those who could not duplicate Bezwoda's results"

And who paid for that "research", pray tell?

Good health to you,

John

.
.