MY comments on "amateur clinical trials"
 

1. have to verify someone has pd? that they are honestly reporting data?
2. who's going to verify that the data is being stored and analyzed correctly? not saying someone is going to lie but mistakes happen.
3. you can't expect most people to wait when "Off", then take the drug, then wait for the affect, think about it. so how are you going to decide on dosage amounts, times, when to report?
4. most clinical trials require doctor approval, are you going to take responsibility for dire consequences?

you've got drug companies spending millions designing trials and analyzing the data using highly trained professionals. this isn't cancer or diabetes or treating high blood pressure where it's easy to take measurements, your're measuring small changes over time in a patient where their pd changes from minute to minute, that requires some knowledge of biology, statistics, science.

so lets say you try a ginseng trial, how many patients will you need and how much of a difference will you need in finger tapping over a control to say it has a significant affect at the 5% confidence level? do you have a normal population sample? can you verify someone took the ginseng? how long do you do the trial?

i always play devil's advocate, i suggest you just propose a trial, say take ginseng, get people to check blood pressure (is it safe) , etc., and then just have people keep a diary and report back in 6 weeks. if you can organize 10 people to do that, then build on that. if you can't, then figure out why, it's difficult enough to recruit pd'ers for regular trials.

i can finger tap differently every hour even when my sinemet is working well so i would think you need more measurements than that, i can also be in a terrible brain fog and finger tap well.

A few suggestions
 

How to get valid information from "amateur clinical trials"?....... I have a few suggestions and comments.

1. have to verify someone has pd? that they are honestly reporting data?

There is no way to be absolutely certain that someone has PD unless you see that person. Inclusion criteria will have to be based on trust and assumption that people who post here and participate in any given study care about getting better and want to have a PD-free life. It is not very scientific, I agree.

For starters, a questionnaire about age, year of diagnosis, symptoms at the time of diagnosis, current symptoms and medications would give some structure to the study. If people are willing, one could do a Skype meeting to confirm PD.

One major assumption is that they are reporting data accurately and honestly. All I can say is that I trust my fellow PwPs.


2. who's going to verify that the data is being stored and analyzed correctly? not saying someone is going to lie but mistakes happen.

In this aspect, I do not see much difference between "amateur clinical trials" and professional clinical trials. Data collected will be with the "PI" (Patient Investigator) just as the "PI" (Principle Investigator) of a clinical program does. Since amateur data will be available to public, it can be analyzed by any patient who has expertise and/or interest in the study, similar to peer review process of a scientific community. I bet we have researchers, clinicians, statisticians etc., among us (who can help....).

To take this process one step further, amateur clinical trial data can be presented in a PD meeting and if the study yields interesting conclusions, there would be even more scrutiny of the data. Since PwPs have no career or financial interests at stake, negative data might even come out!

3. you can't expect most people to wait when "Off", then take the drug, then wait for the affect, think about it. so how are you going to decide on dosage amounts, times, when to report?

These issues can be resolved with detailed instructions, good record keeping and detailed protocols for how to take a finger tapping test or any other tests for PD. Obviously we cannot mess with dosage of meds, times etc.,

We may not be able to pool data from, say all the 100 participants to get a conclusion because of variations in drugs, dosage etc., But we can always measure the improvement over baseline within a given time for each participant. for example, I measure my finger tapping rate after 30min of meds (whatever meds and how many times I take is recorded) for a week or two before I start on a new suppliment. Keep records for 6 months with the new compound. The key is to maintain detailed records. If needed, participants can exchange info in a skype meeting once a month or so.

4. most clinical trials require doctor approval, are you going to take responsibility for dire consequences?

No, unfortunately these patient-initiated trials will be no different than professional clincal trials in terms of taking responsibility for dire consequences! Inclusion criteria: Lab rats who understand "Informed Consent" concept and do not blame others for their deeds.

you've got drug companies spending millions designing trials and analyzing the data using highly trained professionals. this isn't cancer or diabetes or treating high blood pressure where it's easy to take measurements, your're measuring small changes over time in a patient where their pd changes from minute to minute, that requires some knowledge of biology, statistics, science.

Whether it is easy or not, drug companies are not interested in studies we are talking about. And also, we need to start at some point and improvise as we go along. Cannot wait for perfect conditions to test our hypotheses.


i always play devil's advocate, i suggest you just propose a trial, say take ginseng, get people to check blood pressure (is it safe) , etc., and then just have people keep a diary and report back in 6 weeks.


Agreed!


PS: I prefer the term patient-initiated clinical trial rather than amateur clinical trials

Girija

i guess my point is if not done right at the start people will lose interest and you won't know if your results are really valid. so i disagree that you just need to get started and work out the bugs later, that is amateurish research. and if the benefits are so great that you can do sloppy design why isn't everyone taking that supplement/drug already?

there's already websites that report patient opinions about what they are taking, does anyone with pd take what is posted seriously?
http://www.patientslikeme.com/condit...nson-s-disease

here's a simple trial, see what the affect of taking your first dose of carbidopa/levodopa with 8oz. of orange juice or hot water with 1tsp of sugar dissolved to test gastric emptying. if you are using finger tapping,record 10 days without orange juice and 10 days with orange juice. that's something everyone taking sinemet or stalvo could try.

so the question is how long after taking your meds do you start finger tapping and at what time intervals? does the orange juice make you go on quicker, does your on "last" longer? so what if you find out you go on quicker but go off sooner? even this simple test can result in complex results, and just saying you can tap faster 30min after taking your meds might not make the treatment useful.

soccertese,

In an ideal world all research would be professionally run to the highest standards. In an ideal world, there would be well researched answers to everything that we're interested in from grapefruit to ginseng, from coconut oil to forced exercise, from curcumin to milk. In an ideal world, the information would be with us now. Unfortunately, we don't live in an ideal world.

In an ideal world, we would be able to put off making a decision until we had full and accurate information. Unfortunately, we don't live in an ideal world.

When it comes to trying to reduce our symptoms or to slow the rate at which our PD progresses we are forced to make decisions now even though we have limited information.

For instance, I'm interested in curcumin. Do you think I should wait until an "official" trial is completed?

We get anecdotal information from this forum. For which I'm very grateful.

But the gulf between this and "official" information sources is vast. So, the question is: can we do better?

I believe we can in three ways:
- we can aggregate the experiences of people (even two reports are better than one);
- we can measure the effect of an action.
- we can open the data to anyone to mine.

Is this an ideal world solution? No.

Is it a reasonable response to a real world problem? Yes.

On specific points in your post. I'm not proposing that people enter a clinical trial. Rather, I see people doing whatever they normally would do. The only difference is that they report the result of their actions. Of course, people will take different amounts of a supplement, at different times and for different periods. This leads to "dirty" data and the need for data mining.

You mention finger tapping not telling the whole story. You are correct. Are you running my program? In a similar set-up to what I run, Vokear et al. [1] measured "Upper limb motor function" using "the finger tapping test [in which] Subjects had to hit two buttons separated by 30 cm alternately during a 30 second period." They found that in the off state this alone explains 58% of the variance in UPDRS III scores.

Again it comes down to whether to wait for an ideal world solution or to proceed pragmatically.

I do hope you send us your data.

Reference

[1] "Effects of levodopa on upper limb mobility and gait in Parkinson’s disease"
M Vokaer, N Abou Azar, D Zegers de Beyl
J Neurol Neurosurg Psychiatry 2003;74:1304–1307
http://www.ncbi.nlm.nih.gov/pmc/arti...v074p01304.pdf

John

"For instance, I'm interested in curcumin. Do you think I should wait until an "official" trial is completed?"

let's not be ridiculous. that's not what i'm implying. if you've read my posts you would know i've tried about every supplement out there, far more than you have i suspect and i have been taking curcumin for years, can't say i see any overt benefit but maybe it's neuroprotective so i take it. i've tried low dose naltrexone, i.v. glutathione, chelation, etc., etc., etc.

you really didn't read my last post, no point in repeating myself.

soccertese,

You write "you really didn't read my last post". Of course I hadn't when I submitted my post. If you had checked, you would have seen that my post was just 4 minutes after yours. So, I was writing my reply to your original post when you made your later post.

You write "i've tried about every supplement out there, far more than you have i suspect". I'm sure that you're right: I've probably taken supplements on fewer than 50 days since being diagnosed nearly 8 years ago. Though whether taking supplements is a good thing is another matter. It just goes to show that all of us act on limited data, and all of us have an interest in better quality data.

Your idea of measuring the impact of orange juice on Sinemet is a good one. I look forward to reading your results. You ask:
"so the question is how long after taking your meds do you start finger tapping and at what time intervals?"
I would advise starting the test at least 30 minutes BEFORE taking the meds. This let's you form a baseline. I would recommend time intervals of 10 minutes, this allows the area under the curve (AUC) to be estimated. The outcomes are indeed complicated, but if I had to choose one metric, it would be AUC.

I'm glad that you now see the benefits that come from PwP measuring their symptoms.

John

Just some other possibilities...

How to tell some one has PD? Google SWEDD. No one can tell what PD is let alone if we have it. We have no scientific basis to tell that even upon autopsy. There is no proof that patient driven data is any more erroneous than clinical diagnosis.

As to the tapping test, this is the only type of measurement that science and medicine currently offer neurologists, so I do not how that is inherently better than anything patients might come up with.

Laura

We aren't the only ones with a credibility problem
 

There are many things I have personally noted about the lack of "science" in our scientific research, but will just point to the experts:

Please consider this info and see if you still have the same concerns.

Based on the meager results page of a Google search, it seems that not too many people know of Dr. John Ioannidis? He wrote a landmark paper in 2005:

Why Most Published Research Findings Are False.

This is a patient friendlier read in The Atlantic Monthly: Lies, Damned Lies, and Medical Science

Even his critics at Johns Hopkins contend that he is basically correct.

I think that PD research fails on many of his points. I don't mean any disrespect for researchers; they are caught up in a "system" just as much as we are. However, I don't think we can sit back and say they have absolute authority on asking questions, seeking answers, and sharing information. What John and Rick are proposing is not nearly as harmful as an unproven hypothesis becoming the core of research for over 50 years. Maybe this is a factor in why we have no cure?

I will say maybe for legal reasons we need to rethink the rat lab as a source for a group name. 23andme is calling those in PD cohort "Citizen Scientist" what if we took on name "Patient Scientist" or "Impatient Patient" tee hee :D

Laura

laura,
drug companies might purposely design trials that make their new drug look better than an existing mediocre drug but that it totally different than a poorly designed trial that as a result doesn't actually test your hypothesis.

that said, there sure have been a lot of failed pd trials and drug trials in general that have cost billions and billions of dollars.

as far as finger tapping, i'd say if you want to test that as a measurement, measure your tapping before your first morning meds and at 15min increments after 1st meds up to 1.5 hrs for 5 days and see if there is much of a difference.

I think any trial, patient-designed or other, is fatally compromised before it starts because we still don't know what Parkinson's is. Any trial cohort is diluted with people who don't have PD, or have different manifestations of PD.

Until we get some identifiable biomarkers, all else is speculation - influenced by the too-hard-to-control placebo effect (especially by those who are testing their own reaction to pills taken with orange juice).

If we have learned anything from taking sinemet for so many years, it is that symptom control has little to do with halting progression or curing the disease.

A fix for Parkinson's lies beneath the surface; taping before and after downing our pills with OJ will tell us only what we want, or don't want, to believe.

I understand and agree that the methodology for evaluating PD is not good at t his point, no biomarkers, placebo effect, not even a clear definitiion of what PD is. These are the reasons many clinical trials failed.

But does it mean, we as patients need to wait for ideal conditions to check out what makes us feel better? Like John and Rick stated why not just document what we have and try to make it a little more scientific. We are not conducting major clinical trials here to cure PD. Just testing if what worked for Rick would work for a few more PwPs and document those findings the best way we can.

Yes. There are going to be false positives, placebo effects in our experiments. after all, placebo effect is due to dopamine release in the brain. Isn;t that we all want and need? As a patient, I would take a placebo effect if it makes my life a little better.

I have seen and been a part of the research world and I can say that very few scientists feel the sense of urgency for a treatment as a patient would. No one is interested in checking out if medication works better with OJ or pepsi. There are no funds for such work.
IF we want to feel better at this moment, however small that might be, we need to do our own experiments, at least those who are willing to be lab rats/
Girija

not to get stuck in minutia, but i mentioned that orange juice + sinemet not because i think it will actually be beneficial but just as a "dry run" for measuring data, would it actually show a difference and if so, would you actually feel "better". just a trial run to see if you could get volunteers and how the data collection worked out before attempting anything more complicated.

that's an excellent point that we are all different, strong placebo affect, etc., but at the minimum i can see having a testing/data collection system in place that we could use for just testing the different generics out there, being able to document that one generic is worse than another would carry more weight than just saying you feel "worse".
or simply reporting on your experience with a new drug, say the neupro patch or the new extended release carbidopa/levodopa from impax labs when it comes out.

I think there is much value in individual experimentation of what makes us feel good, and then sharing that information. But actually designing and conducting a "clinical trial" around that just seems like playing at science.

I believe the research establishment has also been playing at science for many years; they were looking in all the wrong places and not talking to patients. I think things are better now; talking to patients is one reason science is now looking in the right places.

I think patients play a huge part in the research process. Sharing what works for us with each other and with researchers is vital. I'm not so sure about the value of a clinical trial that cannot control for all of those variables (placebo effect, absence of biomarkers, no good PD definition), patient-conducted or otherwise.

some suggestions
 

In no particular order-

When appropriate, it should be possible to enlist the patient's individual neuro as an observer by means of simple, standardized forms.

We are going to be limited in what we can attempt, especially at first, and that could make us look rather silly ("The neighbor's cat ate our rat!") It might be better to present what we have in mind as triage to identify promising and productive areas to invest the real dollars in. An example might be mucuna as an affordable alternative to ldopa.

Handled properly, the real value here might be the PR angle to force a sense of urgency onto the table. The AIDS activists were not throwing pies because they enjoyed baking. They were getting a message out. We have an easier message to convey - time's a'wastin'! The symbolism of the patient demanding a major role at the table can be a powerful one.

Some people might think I am crazy for the way I experiment, but if I hadn't gone ahead and started my first experiment of makinig fava tops tincture when I was not experiencing so many symptoms of PD....I wouldn't have been able to do it later. I was doing it for the lady that I was taking care of with PD..who was desperate for me to find something natural to help her symptoms. The fava beans worked for her , but long term storage resulted in freezer burn, etc. By the time my first plant tincture was ready to strain ...this may sound very strange to most of you....God had allowed me to start experiencing more distressing aspects of PD (one of them,, having to go to the bathroom every 15-20 min and then incontinence on top of it. Some of you will never experience this problem, but I know others have and know what I am talking about) I was ready to quit driving because my reaction time was getting so much worse (and it was not good to start with!) and other things.... This gave me courage to try a small amount of my tincture of fava plant...what did I have to loose??? I told my patient..".if iI die, tell dad I am sorry ", and took about 1/2 teaspoon of it in hot water. Go to the 4 acres to grow fava thread to read "the rest of the story"...without experimenting ON MYSELF (doing non-clinical trials) I would not be working/driving/and wearing Depends!I certainly would not be farming and still looking for things that help my PD. My brother died in Dec with PD and heart problems....my children might have PD/ and my grandchildren....there are many people outside my family who I love dearly with PD and those that have gone on. I want to do all I can to at least prevent symptoms for myself and others so we can live normal lives without drugs and their side effects. And I will continue my quest as long as God sees fit to give me breath. CRAZY..yes, but I feel good. And, I am not paying a doctor big money to experiment on me. So far I have not killed myself (and if I do, it won't be on purpose ) If I do, tell Dad I sorry..........Love you all Aunt Bean

East of Eden
 

Aunt Bean, I appreciate your tireless efforts. I wish I could gather all your posts together into one book:). Keep growing those beans!

a few thoughts
 

I'm not quite sure what folks mean by "amateur" "clinical" and/or "trials" in this thread but thought I'd over a few organizing principals that I use.

There are at least three buckets mentioned throughout this thread:

• Experimentation with/optimizing "treatments" (evidence based medicine)
• Research to find new treatments (interventional research)
• Learning from patients (observational research) to better understand risk factors, disease progression, disease profile etc

I think our current/traditional ways of doing all three of these efforts has limitations. Doing anything "amateurish" also has limitations.

We seek to improve any/all such undertakings by making sure the questions are relevant, the studies are created in a way in which we have a shot at getting a definitive outcome, subjects are informed and treated ethically, studies are conducted with safety top of mind, studies offer an appropriate risk/return for the patient (I'm sure there are other important considerations).

We believe in some fundamental things..

*interventional trials need to double-blind, placebo controlled to give us the best understanding of impact.

*there are probably better ways to collect more relevant, informative data from patients (in observational studies and in interventional studies) and we need to try new approaches to get that data in the mix. (I will start a new thread highlighting a "research challenge" MJFF launched this week).

*properly powering any analysis is essential or we cannot draw meaningful conclusions. But, some questions lend themselves to more tolerated variability in the responses ... the law of large numbers can be your friend when asking / answering some questions. (This is one of the reasons we want to get thousands more patients signed up for clinical trials).

Anyway, just some thoughts to add to the mix ...

Debi

Amen, Carey!
 

You hit the target right on the bullseye. I don't see how any statistical analyses can be completely accurate until we have a way to positively say that participants have PD.

Can anyone explain that ? Or what if your control sample had PD but was not yet symptomlaetic?

Pegleg writes:

You are right that the results cannot be "completely accurate"; they are flawed in many ways. Let me add my own one: there may be many different forms of PD so the same intervention can have different effects on different people.

But the point is not whether the results are "completely accurate", but whether they are more accurate than what we have now.

At the end of the day we make a decision to take this supplement or not, whether to do this exercise or not, whether to put ourselves in this environment or not. It is better that we do this with some information than none.

Does anyone argue that it is best not to collect data?

John

Just another idea --
 

From what I have read, the Cure Parkinson's Trust proposed testing at least 10 medications already approved for other conditions (and considered safe) but thought to have benefit to PWP's in the next 18 months through a format they called Linked Clinical Trials.

The goal of the program is to rapidly identify any medicatiions which could either be immediately offered to patients "off label" in the clinic or undergo more RCTs to fully characterize their efficacy. Since these medicatiion are already approved in some other capacity, the Cure Parkinsons Trust estimates 10 to 11 years of normal drug development delay would be eliminated.

I think the proposal was made at the Gran Rapids Mi. conference in Sept of 2012.

NT forum members could consider a few options.

Some might prefer to participate in one of the trials. Others might choose to consult with their MDS and try one of the candidate drugs "off label" and report their experiences here.

Either way, I think this proposal addresses the immediate need to fill badly needed symtomatic and disease modifying needs of the PD community.

Some of the top notch researchers on this site can probably come up with the list of the drugs being considered under the proposal.

I know that I will gladly participate one way or another.

I was absent the day they taught science in high school, so I can't address the science of it. Even the whole thing of the double blind, triple deaf, quadruple mute "clinical trial" makes no sense to me; not to mention the sham surgery. They take the person out of the person, and then test the zombie that is left over.
When I fall off my Parkie-horse, I do not first grab the pillbox and call the neuro, I first crawl to the likes of Reverette123 and Aunt Bean for the tech-specs of what I am ingesting blindly and Ginnie changes my soundtrack to "Dislocated Boy" and I read this site to stop feeling sorry for myself and I try to attach my brain to something that looks good, feels good, and is attainable for me; and I get that kind of advice from this tribe where there are people who have tried just about everything. I do not measure anything except number of hours On and number of hours Off and the intensity of both.
So white rats on this site have always provided me with information I do not get anywhere else, and I validate by myself whether or not what worked for others works for me. But I don't do finger tapping (although I could if anyone wanted). I judge for myself the level of incapacity in the past hour compared to the hour before that. It is partly or mostly "subjective" and I know that science does not do "subjective" but I am subjective pretty much all the time, on account of it being me and all.

So I support the White Rat Self Experiments because they capture lots of information of value, as actual end-users in real life.
It would also be a case of "the medium is the message". The medical world will not notice the content of the self-experiments as much as the fact that rogue Parkies are frustrated enough to experiment on themselves.
All of this has already been going on. The changes being proposed are to get some formatting and analysis and commentary accumulated in one place. Too many good suggestions are getting lost in the tsunami of information that the internet brings us.
I hope lots of scientists get to be doubly as blind; but a couple of years ago I could not find a single thing to hang on to, I phoned Rick down in Tennessee and he told me 3 things to do and I did them and went to sleep and got up the next morning and cut down a maple tree.
There was nothing double blind about it, but I crawled out of my swamp and was functional again. And that day I chopped up all my pills and took lower doses more often, and I ingested a small portion of Rick's magic potions, which are already included in his internet signature on this site, and Rick has been evolving that list for years.
There are more Rick's out there that we have not heard from.
It is already happening; it needs some formalization and communication. I support the citizen scientists medium-is-the-message self-evaluation and kitchen-friendly self-medication and spiritual self-realization.
My sound system is on "Shuffle" whereby it plays songs in random order; it just now started playing "Last Matador of Bayonne".
Parkies are the matadors and Parkinson's is the bull. We face it straight on, fearlessly; step elegantly aside when it charges at us with its horns down, and we wait for the moment to kill the Beast.

testing "safe" compounds / "repositioning"
 

This is a growing area of interest throughout drug development. NIH recently launched a significant effort across all diseases.

MJFF has been funding "repositioned" compounds for several years in preclinical and clinical stages of research -- so much so that we decided to launch a specific program (and draw more attention to it within the PD field) a few years ago and have renewed it again in 2013. You can find more information here. https://www.michaeljfox.org/foundati...254&category=4

Debi

Data collection: PDMeasure
 

Across a number of threads, we've discussed and we've argued about data collection. It seems to me that the time has come to either do it or to move on to something else. Ultimately the best evidence is seeing something in action. As mentioned before, I've written an integrated set of programs, PDMeasure, that allows us to enter data, do tests and see the statistics.

I propose we start by checking whether PDMeasure is fit for purpose.

If you want to take part go to:
http://www.parkinsonsmeasurement.org/PDMeasure

If you've not already done so, you will need to register. Registering involves providing a user name, preferably not your NT ID, and password. This allows the data to be stored anonymously, but makes it possible to aggregate a person's entries.

If you have registered already (13 people have), please make sure you have done both surveys (only 4 people have).

For the next week I propose that we do the test at least daily. This will allow us to see if the measurement tool give useful results.

PLEASE NOTE
1. all data is visible to everyone.
2. healthy people and PwP can enter data.
3. The data can be seen at:
http://www.parkinsonsmeasurement.org.../writeData.php
4. A simple statistical analysis can be seen at:
http://www.parkinsonsmeasurement.org...Statistics.php
5. Bob Dawson makes a good point that he records hours "on". Data such as this can be input in the extra information field of Test 1.

John

This thread has made good reading. Especially where people point out what is not known about the condition "commonly known as PD". My only addition to the various opinions on this subject is that I fail to see how there can be progress without patients being viewed as 'whole people', that is not just as neuro-defective in some way.

To illustrate how observation can go missed even between doctors and their peers, I cite my own personal experience of being treated with an anti-cholinergic medication by a urologist. This well-repected specialist was not surprised when I said that the said medication had a positive effect on my pd symptoms, especially mobility; he had observed this in other patients over years. This information did not go down well with my neurologist, who brushed it aside. Yet over the years I have discontinued and re-started this medication several times, mainly because of visual and oral side-effects, and each time on returning have been able to make the same observation.

If such things are so hard to share between disciplines, it seems an uphill battle for the citizen scientist, patient or impatient! Yet we have a condition that affected us in a multi-systemic way. I would ask where are the MDS who really understand this and communicate with other specialisms. A question I believe I was asking at least 5 years ago. At least if patients were able to say I use 'x' because it helps, it would provide some kind of statistic that showed what was helping, rather than stabbing in the dark to impose a set of drugs that may or may not be of use at all. We have the means to collect that kind of data, raw though it might be. Orthodox or not, it is still relevant.