Here are 4 threads on randomized controlled trials (RCT) that may be useful for those interested in doing one, or learning about the process and what it takes. #MedTwitter#MedStudentTwitter
1. The process is not easy. Certainly not for investigator initiated RCTs in the US.
2. Here is an example of the process from start to finish of an RCT we did in @eaonc@SagarLonialMD
It gives you an idea of the process for investigator initiated NIH cancer trials— which is totally different from a Pharma company sponsored Pharma company run trial.
3. RCTs can be done for various reasons including incremental advances and drug approvals. Many of these are well done by Pharma. And Pharma has the resources to pull it off. But we also need strategic investigator initiated trials to answer important clinical questions.
4. Here are RCTs I have worked on. A mix of investigator initiated trials and Pharma trials. I learnt many lessons during the process. Luck was always important, as was the help of patients, collaboration with superb colleagues, and hard work.
In the year 2000, a few of us attended an angiogenesis meeting in Boston. We were there to discuss thalidomide
But a side meeting that evening led to trial that went on to get Velcade FDA approved for myeloma. @NEJM
Story in thread.
Velcade (bortezomib) was first introduced to cancer research by the name PS-341.
It was a novel proteasome inhibitor developed by Julian Adams and colleagues a a potential anti cancer agent. @CR_AACR @AACR aacrjournals.org/cancerres/arti…
The ubiquitin-proteasome garbage disposal pathway in cells is a Nobel prize winning discovery.
Proteins that need to be degraded are tagged with ubiquitin tails. Tagged proteins are degraded by the proteasome complex. (This review has details )
The fascinating story of Thalidomide: how this most notorious drug on the planet, banned in the 1960s, made an incredible comeback and revolutionized the treatment of myeloma.
I will also highlight one person whose role is not recognized: Without Dr. Leif Bergsagel there will be no thalidomide for myeloma.
Read on #MedTwitter
The thalidomide story has many takeaways and lessons.
It shows drug development from bedside to bench and back to bedside.
It shows the power and impact of astute clinicians
It shows the power of investigator courage
The role of serendipity
But let’s start at the very beginning.
Thalidomide was synthesized in 1954, and then developed as a sleeping pill by the German company Chemie Grünenthal in the 1950s.
At the time the only sedatives available were barbiturates which had risks of intentional or accidental overdose.
Because thalidomide was felt to be a drug that cannot cause death due to overdose it was marketed as one of the safest sedatives.
By 1961, it was sold in over 40 countries as a sleeping. It was also tragically used to control morning sickness of early pregnancy.
AQUILA trial for high risk smoldering myeloma published in @NEJM today.
@thanosdimop
Personally for me, it is a huge milestone along 25 years of work that started in 1998. #ASH24 #ASH24VR
This story below may help those interested in a clinical trialist career. 1/
In 1998, as a fellow @MayoClinic I was keen to determine if early intervention delayed progression and improved survival in SMM. #ASH24
In 1999, with the help of Tom Witzig, I led a small phase II trial of thalidomide for SMM. @LeukemiaJnl 2/
I was then so fortunate to examine the natural history of SMM, with the legendary Bob Kyle. Honored to be last author on @NEJM paper that also provided data that most progressions occur in the first 5 years of diagnosis.
The start of the concept of high risk vs low risk SMM. 3/