
L-Theanine Experiment (1 Month) - chrisrxth
http://doubleblinded.com/experiments/l-theanine-experiment-1-month
======
rgejman
This website almost certainly violates FDA rules on human subject
experimentation because it collects data on the effect of a drug on human
subjects. I would stop working on this project until you have advisors (and
lawyers) who have experience with regulatory oversight from the FDA. At the
bare minimum you are going to need (a) procedures to gain _informed_ consent
from trial enrollees and (b) an Institutional Review Board (IRB) to sign off
on your trial. Depending on the drug, you might also need an FDA waiver to
conduct the trial.

The PhD student (Rob Wagner) listed in the about section should have had at
least one course on the responsible conduct of research. This course is
required for most (all?) scientists working under a training or research grant
from the NIH. Design and implementation of clinical trials--along with the
ethical and legal issues involves--is standard fare for these courses for
precisely this reason!

~~~
chrisrxth
Thanks for the thoughts. We've spoken with a lawyer who specializes in FDA
issues. We will have informed consent waivers for participants.

Rob does have formal training in scientific ethical issues and is more than
competent on the subject.

Also, L-Theanine is something that you can purchase at the grocery store as a
food supplement and it has an excellent safety record and no known toxic
dosage.

If it makes you feel better, we are a supplement distributor that happens to
help you record whether or not the supplements actually work.

~~~
mattwinslow
The other comments are on point. From my perspective as someone in the digital
health / clinical research industry, the site (as is) raises a bunch of red
flags:

\- There's no indication this study has received IRB (Institutional Review
Board) approval, which is a baseline. Here's a handy reference when asking the
question, "Does my research need IRB approval?":
[http://www.irb.umn.edu/research.html](http://www.irb.umn.edu/research.html)

Based on several factors, the study/experiment qualifies as research (it meets
the requirements for being a systematic investigation, contributing
generalizable knowledge, and involving human subjects). IRB review/approval
can be fairly straightforward, but does cost a non-trivial amount of money.

Chris, if you need to work with an IRB, I recommend getting in touch with
Copernicus Group ([http://www.cgirb.com/](http://www.cgirb.com/)). I've worked
on 20+ projects where they've been the IRB and they've always been responsive
and pretty open to innovative ideas.

Echoing rgejman, if you don't have IRB approval, stop everything. Now.

\- There's no mention on the site of participants completing an informed
consent, which should really be done prior to collecting their money for the
kit.

\- Has any thought been given to how the team will handle adverse event
reporting? This deserves serious consideration and is sometimes overlooked
(there are a slew of FDA guidelines/regulations around this). Even for
something that seems benign or where "nothing could ever go wrong" \- you'd be
surprised.

\- The site doesn't instill a ton of confidence that data security is a high
priority. Using SquareSpace to host the public facing informational portion of
the site isn't necessarily a problem, but it leads me to wonder how the team
is handling surveys and how the survey data will be stored. It seems like
participants will likely provide personally identifiable information (PII) and
personal health information (PHI) within surveys, and that's when things start
to get a bit more interesting.

It's certainly possible to use an off the shelf survey tool (like
SurveyGizmo), but there are a few more hoops you'll have to jump through. Take
a look at the following link: [https://www.surveygizmo.com/survey-blog/online-
survey-hipaa-...](https://www.surveygizmo.com/survey-blog/online-survey-hipaa-
safe-harbor-certification/)

\- There doesn't seem to be a privacy policy. The About Us page mentions, "We
will have a complete policy online before we start taking orders for the first
experiment." The SquareSpace checkout appears to be up and running, but I'm
unable to find the privacy policy.

There's a more or less standard process for designing, developing, and getting
a study out the door (highly simplified, and skewed heavily towards direct to
patient studies): 1\. Develop your protocol. 2\. Get your protocol approved by
an IRB 3\. Develop/configure the tech to implement the mechanics outlined in
the protocol (this can be done in parallel to IRB review and/or protocol
development) 4\. Recruit patients 5\. Collect informed consent, enroll
patients 6\. Collect data 7\. Everything else...

One of the tricks here is that _all_ of the content a patient might see has to
be IRB approved.

Want to run ads soliciting your study? They have to be IRB approved.

Want to optimize your ads? Make sure your content is submitted modularly for
review (ie, list all your headlines, body content, and images separately - and
throw the kitchen sink at any variations you can think of to save yourself
another round of review).

Want patients to pay for their kit via a SquareSpace checkout? Probably
requires IRB approval, and likely needs to occur _after_ a participant has
completed an informed consent doc.

Need to send password reset emails to patients in the event they can't
remember their login to access the study survey tool? Has to be IRB approved.

If you wanted to use efficacy tracking as a marketing tool for your supplement
business, you might have a bit more leeway if you were to reposition what
you're offering. You could (and there's a good chance I'm wrong as this is off
the top of my head) simply offer your customers a tool to track the effects of
their supplements. This would also help you with reorders by providing an
adherence mechanism.

Unfortunately, you'd likely have to scrub using the Double Blinded site,
referring to what you're offering as an experiment, or mentioning that the
results will be aggregated and published. Data protection issues would still
be a serious consideration though.

All of that said, the concept of citizen science and open/transparent studies
is very cool. It's just a (minor) hassle to dot all the i's and cross all the
t's.

Also, brilliant idea to offer customers a way to track efficacy. I've been
toying with similar ideas, so it's cool to see someone else implementing
something.

~~~
volkhavaar
This is an incredibly informative and useful post. Thank you.

~~~
mattwinslow
Thanks! Digital health can be incredibly fun and rewarding, but there are
plenty of opportunities to run head first into walls you may not have realized
even existed.

Aside from the ethics considerations, privacy regulations (and the desire to
tread conservatively) can lead to some odd implementation
decisions...especially if you're coming into the industry from a general or
consumer oriented tech background.

I once worked on a medication adherence project for patients in Italy where
patients needed to complete bi-weekly assessments and generally track their
medication adherence. We set up a secure portal/website for patients, but were
prohibited from emailing them reminders when their next assessment was due.

The sponsor (aka pharma co) was extremely conservative re: patient privacy
laws and more or less left it at, "well, the patient will just have to
remember to return to the website, log in, and complete their survey at the
appointed time." After a couple of months of sub-optimal survey completion
rates, they re-evaluated their position and let us send out survey reminder
emails.....which is a baseline thing to do when you need to retain
participants over the life of a study.

Oddly enough, this was for a commercial project (medication was available on
the market, physicians were referring their patients to this website as a
value added sort of service) and the commercial side is a bit more wild west
than phase 2/3 research. Well, as wild west as the pharma/clinical research
industry gets :)

There are parallels between customer acquisition/retention in SaaS and patient
recruitment/retention in clinical trials that are pretty interesting...but I
think most folks on the Saas side would think the healthcare folks are trying
to solve problems with one (if not two) hands tied behind their backs - and in
some cases, wouldn't be wrong in thinking so.

------
Steer
I love the idea, but the execution seems less than ideal. Besides the research
ethics question posed in another comment, what is the dosage of L-Theanine in
the capsules? What kind of responsibility does the company take for possible
side effects? I understand the side effects should be mild or non-existant in
the experiment for L-Theanine, but just a discussion around that issue would
be nice.

Again, I want to stress that I love the idea, but the web site just feels
incomplete.

~~~
vox_mollis
_What kind of responsibility does the company take for possible side effects?_

Probably the same kind of responsibility taken by green tea manufacturers.

~~~
DanBC
Green tea sellers don't make medical claims for their products; green tea
sellers don't enroll people in "research".

~~~
chrisrxth
We make no medical claims about our product either - we only reference
existing science.

~~~
fabian2k
"[...] and is known to promote relaxation without sedation. It appears to be
effective at this as well as reducing stress at standard dosages."

I would read that as a medical claim, it doesn't matter if you quote another
site or not.

The claim about stress seems to be based on experiments in rats and a single
study with 12 participants.

~~~
ddeck
This made me curious so I checked the FDA site. In case anyone else is
interested:

From a very cursory review, it appears that health claims on the packaging are
quite heavily regulated by the FDA[1], but advertising for dietary supplements
and foods seems to fall outside their mandate and regulatory responsibility
lies instead with the FTC:

 _" The Federal Trade Commission (FTC) regulates advertising, including
infomercials, for dietary supplements and most other products sold to
consumers. FDA works closely with FTC in this area, but FTC's work is directed
by different laws."_[2]

I'm not sure what's on the bottle, but presumably the websites falls under the
jurisdiction of the FTC. A brief review of their site seems to indicate a far
more relaxed approach is taken. For example:

 _" The FTC's standard for evaluating substantiation is sufficiently flexible
to ensure that consumers have access to information about emerging areas of
science"_

 _" These factors are often weighed together to ensure that valuable product
information is not withheld from consumers because the cost of developing
substantiation is prohibitive"_

 _"...the FTC gives great weight to accepted norms in the relevant fields of
research and consults with experts from a wide variety of disciplines,
including those with experience in botanicals and traditional medicines"_ [3]

[1]
[http://www.fda.gov/Food/IngredientsPackagingLabeling/Labelin...](http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm111447.htm)

[2]
[http://www.fda.gov/Food/DietarySupplements/QADietarySuppleme...](http://www.fda.gov/Food/DietarySupplements/QADietarySupplements/#how_ad)

[3] [https://www.ftc.gov/tips-advice/business-
center/guidance/die...](https://www.ftc.gov/tips-advice/business-
center/guidance/dietary-supplements-advertising-guide-industry)

------
zxexz
I tried taking L-Theanine for about 5 days. 30 minutes after taking it each
day, I would get very nauseous and usually throw up. I tried varying the
dosage from 200mg down to 100mg and then 75mg, I would still get the nausea,
no matter if I had an empty stomach or not. I also get the same symptom when
drinking more than a cup or so of green tea, and has for years (though I do
remember being able to stomach the stuff in the past). It would be interesting
to hear if this happens to anyone else.

~~~
partisan
I get the same effect from drinking Starbuck's "Awake" or black tea, whatever
they call it now. An empty stomach usually makes it worse.

~~~
zxexz
That's interesting. Now that I think of it, the nausea feels exactly like what
you get from ingesting the tannins in overbrewed black tea. I just assumed my
nausea from drinking green tea and from L-Theanine (which I know that green
tea contains in a non-negligible quantity). Maybe levels of tannins in green
tea are higher than in black tea? In that case the nausea from L-Theanine may
be unrelated. Maybe it's a combination of both.

~~~
partisan
I think you might be on the right track, but I drink their green tea now and I
don't get the same effect. I also drink overbrewed Twinings english breakfast
tea with no negative effect.

------
OopsCriticality
Yikes! I'm a bit disappointed and slightly surprised that there's no
discussion nor consideration of research ethics appearing anywhere on that
website.

~~~
chrisrxth
You bring up a good point! We will be adding some outlines about ethics soon.
Thanks for reminding us of the importance!

~~~
robbiep
I'm sorry, you have a website called doubleblind, you are asking people to pay
to participate in the study, and you need to be _reminded_ of the importance
of thinking about ethics?

There's a reason why science and medicine don't move the same way Web 2.0 does
(ie move quickly and break things). It's because people have died from poor
implementations, and people trialing drugs are prone to exploitation from
unscrupulous merchants.

Now I'm not saying there's anything wrong with your study, or your proposed
aims. But if you want to be taken seriously and not shut down by whatever
regulatory authority governs your territory, you need to think long and hard
about this on both this study and any future studies/products you intend to
sell.

Do not screw this up, and do not make the mistake of approaching human health
and clinical trials as though something critical like ethics review is
something that can be 'patched' further down the line after the release date

~~~
chrisrxth
We chose L-Theanine because it has an excellent safety record, is well
studied, and has no known toxic dose. We are very aware of safety and ethics.
There are many nootropics and supplement companies safely distributing the
same L-Theanine.

While we work through our protocol we will continue to dive into ethics and
safety.

~~~
robbiep
What you have stated here you have stated in your previous thread announcing
doubleblind and presumably elsewhere. I don't have an issue with what you are
choosing, or why. In fact, it doesn't really matter.

What matters is that you have a clear and transparent ethics approval process,
that you clearly state the steps your protocol had been through, and
preferably that you submit your protocol to a human ethics review board, and
identify that process openly and transparently.

It sounds like you have already developed your protocol, since you are
offering your product for sale shipping from the start of this month. So have
you written an ethics proposal? Have you considered submitting it to a HERC?
Or are you 'continuing to dive into ethics and safety' now that you have been
'reminded of the importance' of it?

Don't get me wrong, I think your idea and platform is potentially great. But
it really seems that you haven't thought about this, and now you're trying to
scramble?

If you don't have a science background and aren't partnering with anyone who
is, I'd be more than happy to lend my 2c outside of this thread (see profile).
Otherwise, I wish you every success with a full and detailed examination of
your ethics approach. Medical research (which you are conducting by calling
your product an experiment) has a poor history when it comes to blurring the
lines between researcher and pharmaceutical company/monetisation, of which you
could be said to be doing both at the moment.

------
Robadob
Interesting concept, shame it's limited to the US (understandable due to
dubious legality of shipping unclassified chemicals between jurisdictions).

Been interested by the apparent 'attention enhancing' qualities of L-Theanine,
although not gone as far as purchasing any. By coincidence someone got me into
drinking green tea a couple of weeks ago, I haven't noticed any visible
change. Although I expect my problem is concentrating on the right thing,
rather than simply failing to concentrate.

~~~
arsenico
From my personal experience, L-Theanine, coupled with caffeine, produces very
serious results in terms of negating bad coffee effects, increased focus and
productivity, and better sleep

~~~
Legogris
Same here. A couple of pots of strong sencha (Japanese green tea) give me a
huge boost in energy and mood, without the negative effects of derealization,
tunnel vision and restlessness I get from too much coffee.

------
matt504
Maybe this actually part of a study to research whether having your research
subjects pay you (rather than the other way around) has an effect the results
of a study.

~~~
chrisrxth
Could you elaborate?

~~~
matt504
Maybe they are taking the money that people pay him on this side and paying
some other research subjects to do the same thing and is going to compare the
results.

It's weird to ask people to pay to be part of a study. So maybe that is
actually part of what this person is studying.

Maybe all the capsules are placebos and they are studying something else.

Can you tell I like conspiracy theories? :)

Oh I just noticed you are the person who posted this. You should do that, if
this isn't what you're doing.

------
NietTim
Hey! I've been taking L-Theanine for the past month. It feels to me like I've
been waking up with a clearer mind, but it's super hard to know if that's form
the l-theanine or just in general the change in the weather. So many
variables.

~~~
chrisrxth
Indeed it's difficult to tell - exactly the reason why a double-blinded trial
on yourself can help you determine if it's making a significant difference or
not :)

------
detaro
Show HN when the idea was presented:
[https://news.ycombinator.com/item?id=10401698](https://news.ycombinator.com/item?id=10401698)

------
nicw
Looks promising. While it may seem obvious, I would spell out what double-
blind means, the problem it solves, and how it is used elsewhere. That then
sets you up to point out how doctors use these study types, adding
credibility.

------
Lewton
I absolutely love this idea. Are you gonna do a trial every month? Any
schedule for which trials you're gonna run?

~~~
chrisrxth
We're going to keep adding more trials - but there's no timeframe for when you
have to start and end the trial. You can order it and start it whenever you
receive it in the mail.

------
filleokus
I also love the idea, would really like to try it! Any chance to get it
shipped outside the US (I live in Sweden)?

~~~
chrisrxth
Not yet :( Like Steer said, you can still order Theanine independently of our
company but I can let you know when we are ready for international orders if
you send me your email!

------
dbcooper
How do you propose to analyse the data you collect?

~~~
doobiedowner
I'm guessing that they're more interested in the collected cash. It's all
about the chee$e!

------
geoffwoo
cool concept. interested in seeing the results.

