Conclusion

You may want to ask how is it possible Dr. Halegoua-Demarzio has 5 star Google  reviews  and not a single person ever complained about her?  Most reviews say she listens to patients. She is not a psychiatrist as far as I know.  Most reviews are from people who never review anyone and some don’t even have real name. All reviews at Jefferson are controlled by Jefferson so I would completely ignore them. Answer lies to sample population she gets for her trials.  In Pennsylvania 69% of adult population are not college educated. People have a tendency to trust doctors. Prospective participants should understand that she is not their doctor. People tend to believe government, specifically FDA, is there to protect them.  People generally don’t have inclination to research and ask for second opinion. Most doctors you ask if you should be on clinical trial will say it more likely to hurt than benefit you. That what I was told.  Most prospective participants will have no idea that only very small percent (maybe less than 58%) of clinical trials succeed. Failure rate in NASH trials is much higher. Few prospective participants will research best trial for them, read business analysts reports, research publications. It is almost impossible for most.  And even then it may turn out that the best trial for you is thousands of miles away. Will you move? Obviously not. And then you have your friendly investigator peddling you her trial because company that is a leader in NASH trials with great results did not give her business. Is there a reason for getting mediocre trials?

And then investigator will try to scare you how bad your disease will get if you don’t get on a trial. Lets say you have stage 1 fibrosis. It takes 6-7 years progress to next stage.

By the time it gets really bad FDA may approve NASH drug. This is what I was told “The natural history of progression from F3 to F4 disease (based on results from prior Gilead simtuzimab studies) is approximately 20% by 30 months.   The risk of F4 disease progressing to a clinically significant clinical event is also approximately 19% over 30 months.” This is why I decided to stay away from trials and concentrate on losing weight because likelihood of benefitting from study is very small and chance to get hurt by it a lot greater.

And lets say you did all homework and decided to participate:

1. Then you should consider finances of the company. It may be less of concern with big pharma. But huge concern with small biotech company especially with limited pipeline (drugs in development). Take Galmed, they did IPO may be 5-6 years ago and raised 70 million on Nasdaq. They continue to burn money and continue to raise more money on Nasdaq by issuing more stock. Last offering 2/21 they were able to raise 9 million.  This is nothing for company that needs to conduct phase 3 trial with expected enrollment of 2000.  I read average company expected to spend 20k on each participant in NASH trial.  More stock they issue more difficult is to raise money. It is real possibility company can run out of money and stop trial.  If you Google “biotech cash burn reporting websites”, you can find website to get free trial and estimate if company you are considering has enough money to complete trial.  That website just takes information from financial reports files with SEC. Bottom line if company can’t get money, trial will be stopped.  Do not even think to rely on investigator opinion. They have no clue.
2. There is always wording in informed consent that allows investigator to remove you from trial for any reason. Or as they call it your best interest, which really means investigator or sponsor best interests.  It is unlikely investigator or sponsor will agree to put specific reasons you can be removed from trial. But remember they can throw you out at any time without any reason. Just make sure you are ok with it. From my experience it hurts like hell to be treated like piece of garbage.
3. Look for wording promising you 5-7 years of free drug. This is just marketing ploy to sign you up.
4. Make sure you have guarantee in writing that all tests investigator receives will be shared with you.
5. Make sure you have health insurance. It is unlikely investigator will agree to cover your medical expenses if you get hurt from investigational drug. But process of going after sponsor should be outlined. Make sure you have everything including contact information. And verify it directly  with sponsor. Obviously with small company like Galmed you should absolutely have  health insurance.
6. You need to make decision if you want to be in trial where sponsor is breaking law and not reporting  results on clinicaltrials.gov. If you decide to take risk with such company make sure you get all marketing materials from investigator and read business analysts reports to see what brokers told investors about success of specific drug. You should ignore all reports done by brokers that sell (underwrite) sponsor stock.
7. You need to have clear understanding how FDA approves drugs. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-continued To summarize there is very little FDA involvement after IND is granted (which is unlikely you will ever see) to multiyear process that leads to NDA application. Where is FDA role in this process that takes years with thousands of people taking investigational drugs for any given trial? To the best of my understanding is in tiny amounts of audits I already documented in my FDA post. Ask your investigator who approved whatever clinical trial phase you considering to be on. And see how she/he will answer. You may be told you have nothing to worry, DMC is in charge. While you will unlikely to know if DMC actually exists for your trial, this article shows how many things can go wrong https://www.nejm.org/doi/full/10.1056/NEJMra1510066 In 3/18/21 earnings conference call Galmed CEO announced “I’m happy to inform you today that the addition of the open-label part to our ongoing Phase 3 was approved in the US, Canada, Australia, UK, France, Belgium, and Spain and is expected to be approved in the coming weeks in Israel, Korea, Turkey, Mexico and Chile”. If you know which entity approved open label please post in comments below
8. You need to understand every word of informed consent which will be totality one sided in favor of sponsor and investigator. Fact that it was approved by IRB and ethics committee is useless. They are all in it together to take advantage of you
9. You should ask Investigator about purity of investigational drug. Sponsor suppose to disclose it in Investigator handbook.  And you should ask question such as “what is half life of real drug I may be taking?” Knowing half life is important for many reason including participation in any other trials as long half life will preclude you from some trials.  If answer is “proprietary”  as pretty much what Cindi Miller was answer to almost every question I asked, tell investigator to take that drug and shove it in whatever part of his/her body you think is appropriate.  And investigators will know thru epic system or social networking about your prior trial participation
10. You should look into using existing approved drugs off label to treat NASH. I started to look in Ozempic but side effects scared me.
11. You should pay close attention how you are qualified for trial. Currently standard set by FDA is liver biopsy. Most likely you will have fibroscan, MRI and then liver biopsy. I did not have MRI and I think it is mistake and probably was trial design by Galmed who wanted to save money on testing. I was told that liver MRI in clinical trial can cost $5000, so if sponsor of your trial wants you to go straight for biopsy and bypass MRI, knowing what I know now I would look for another trail. You want to have as much non evasive testing as possible before you agree to have liver biopsy. This may include PRO-c3, ELF tests, new devices that cleared by FDA based on handful of participants. You may hear that you don’t need biopsy and your disease diagnosis is clear enough for you to start on trial. But at the end you will be taking investigational drug for disease you may not have. Biopsy considered gold standard and don’t let anyone talk you of it. In my opinion possible danger of biopsy is magnitude of factors less than “safe” investigational drug you will be recruited to take. There are white papers circulating in Hepatology journal written by investigators probably with push from sponsors trying to convince FDA that liver biopsy is not reliable way to qualify for trial. I suspect this is done because sponsors can not recruit and investigators can not get paid due to such strict requirements as biopsy. I doubt it is so hard to run study presented in hepatology journal to create results someone want. I did not read any specific article on this subject as they are not free. I urge you to not fall for this tactic if FDA caves in and allows less strict testing to qualify for study. You are qualifying for study to take potentially dangerous investigational drug. You need to make sure you really have disease you are told you have. Biopsy is gold standard and if you told you don’t need it you may want to look for other study. Liver regenerates. You want to have best diagnosis possible. And you want to make sure your slides examined by more than one pathologist to make sure they arrive to the same conclusion. Insurance usually pays for second opinion, it is not that expensive to send slides some place else to make sure you have diagnosis you told you have.
12.  If you still need answers before or when in a trial I would advise not to look for message boards that suppose to help patients. I found one called smartpatients. Run by person stating to be former Google executive. It has moderator, totally unqualified person that most experience is in virtual handholding and no substance.  You would expect someone with resources previously working for Google will spend money to get someone qualified to help people to navigate thru clinical trials. When I brought it up I was promptly removed from the message board. Most people on smartpatients board with advanced cancer. But what struck me the most is one person asking if she should participate in some Phase 1 study because her potential investigator told her that investigational drug will kill her cancer. Not single person including myself told her that investigator has no way of knowing and Phase 1 is extremely dangerous, this is why it is phase 1.  But this shows how no one should believe investigators on efficacy and safety of investigation drugs unless they can show something written to support that statement. And then you should still consider who wrote it and why.

About ½ century ago clinical trials were conducted on prisoners.  Maybe best leave to that crowd.

They can always advertise here for professional guinea pigs here

You need to think long and hard why you want to get involve in trial.

Global pandemic, life threatening disease such as cancer is one thing. NASH, I am not sure risks are justified. And fact that everyone is against you is very important consideration.

Please look at results only and take them to a doctor that doesn’t do trials. And assess your risk. You life is not to make investigator and sponsor rich. Sponsor will make hundreds of millions with successful NASH drug.  Assuming you are not F4 which probably will disqualify you from most trials anyway you should try to lose considerable amount of weight and see if your liver enzymes got better. I know easier said that done, but I was able to do it once.  You should never ever forget you can die from investigational drug. Phase 2 is done on few hundred people. What kind of indication of safety is that? And that is assuming best case scenario. No biases in reporting results, etc.

If you still decide to participate in trial you have to be ok  with idea you are nothing more than Guinea pig, don’t expect anything out of investigator and sponsor. You can be thrown out at any time. You have nobody to complain to. You will hear “you were told everything in consent, you signed it“. You are unpaid volunteer.  You are to be used and thrown out when we no longer need you for whatever reason. 

I don’t think there is entity left that I did not complain, Jefferson CEO  Klasko, Jefferson President Webster, WCGIRB, Jefferson ethics committee, FDA, PA AG, senators, congressman, state representatives.  Not even a response. The most I got out of Jefferson. We are still going to treat you as a patient (meaning we want your insurance money), don’t think because we thrown you out from clinical trial it has any bearing on your continuing treatment (abuse in my experience) at Jefferson. Needless to say I left Jefferson entirely.

The only place I have left to complain about Dr.Halegoua-Demarzio is PA medical board. I am sure result will be no different from all my other complaints.

I decided to stay away from trials and let someone else to endanger their lives from taking investigational drug. There are 40 trials going on now, most phase 2. Which I would never do anyway. Most phase 3 failed so far.

NASH drug from Intercept probably will be approved this year. I don’t want this drug, NASH / fibrosis improvement is small, risks with increased LDL is huge. Madrigal drug looks promising but reducing fibrosis is not primary endpoint. Akero, NGM, Hanmi reporting impressive results but all are Phase 2. All of them injectable. Number of big pharma doing trial as well. So I will take my chances and wait for approved drug.  And I will read everything about that drug to decide if I should take it.

I understand new drugs need to be developed and they only way to develop them is to conduct clinical trial. But unless clinical trials conducted in transparent matter, there is liability insurance that sponsor must pay for,  Investigator employers are responsible for medical treatment of trial participants if there is even small connection to investigational drug, FDA audits all sponsors, all FDA guidance has  legal enforcement and trial participants actually get paid money that have some resemblance of what investigators, IRBs, DMC get and possibly some loyalty payments if drug is approved and becomes huge financial success, I no longer want to be taken advantage of. But how this dream above can become reality?  By Guinea pigs demanding to be treated like human beings. This is how change is made. You dont need them, you are a tool to make billions from approved drug.  They cant do it without you. Clinical trials participants union anyone? There are 100,000 of us at any given time. Lets change US from green to red.

There is big debate going on about paying clinical trial participants to participate in trials. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728432/

I think it is just pretense to save money for sponsors.  Take Galmed, I got $50 for each blood draw visit and only if Jefferson actually able to get blood from me.  I actually had to come back at my own expense because Jefferson does not train nurses to take blood from people with difficult veins. So lets say Galmed would pay me 100 for visit or 200 or more for each visit. Paid for my parking. Would that be enough to make me risk my life for investigational drug?  There is no money that would make me to do that.  I decided participate for 67% chance of getting real drug.  Would it be incitement to some people? Probably. Did NIH/FDA/IRB ever do study what % of sick people do it for money? No and they never will because it is a lot easier to offer some idiotic logic in interests to save money to cheap skates like Galmed (that has no problem paying over million to ceo and ½ million to other executives). I saw informed consent of other nash sponsor and they paid 3x of money Galmed paying plus parking and hotel. And even with that 99% of intelligent people would not consider as enticement.