What Does The Walls Have Ears Mean?
Home » Phrase and Idiom Dictionary » What Does The Walls Have Ears Mean?
Definition: Be careful what you say because someone might overhear you.
Imagine that you want to gossip about someone with your friend, and you think that you are alone in the room. If you start to say something private, your friend might warn you that someone is eavesdropping by saying that the walls have ears.
This implies that even when you think no one is listening, someone may still be spying on you.
This expression first appeared in English in the 1600s. However, some sources speculate that it comes from a story that is much older. The origin story may date back all the way to around the year 400 B.C.
The warning allegedly refers to the story of Dionysius, the Greek tyrant of Syracuse (400-367 B.C.).
Dionysius reportedly constructed a cave in the shape of an ear so that he could hear what people were saying in other rooms. His listening posts connected palace rooms that allowed him to hear what his prisoners said from other rooms in the cave.
Over the years, other historic places, including the Louvre in Paris and Hastings Castle in England were said to have such listening posts.
This example shows two women discussing some office gossip.
Bella: Did you hear what Tina did at the meeting? She's so ridiculous.
Hannah: Wait! Did you hear that? I think someone may be listening in on us. The walls have ears here. Maybe we should wait to discuss this until we leave for lunch.
Bella: Okay, good idea. Let's do that.
The following example shows two college students whispering in their music class.
Hanh: I didn't have time to study for this test. Do you mind if I copy your answers?
Hanh: What's the problem? No one can hear us.
Zhongyi: Yes, they can. The walls have ears. If we are going to talk about this, we need to go somewhere more private.
This excerpt is from an article about business trip etiquette.
The second example is from an article about professional hockey.
The phrase walls have ears is a warning that means someone might overhear a private conversation.


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text:
require "unit_spec_helper"

describe Rpush::Client::Redis::Apns::Notification do
  it_behaves_like 'Rpush::Client::Apns::Notification'

  it "should validate the length of the binary conversion of the notification" do
    notification = described_class.new
    notification.app = Rpush::Apns2::App.create(name: 'test', environment: 'development', certificate: TEST_CERT)
    notification.device_token = "a" * 108
    notification.alert = ""

    notification.alert << "a" until notification.payload.bytesize == 2048
    expect(notification.valid?).to be_truthy
    expect(notification.errors[:base]).to be_empty

    notification.alert << "a"
    expect(notification.valid?).to be_falsey
    expect(notification.errors[:base].include?("APN notification cannot be larger than 2048 bytes. Try condensing your alert and device attributes.")).to be_truthy
  end

  it "should default the sound to 'default'" do
    notification = described_class.new
    expect(notification.sound).to eq('default')
  end

  # skipping these tests because data= for redis doesn't merge existing data
  xit 'does not overwrite the mutable-content flag when setting attributes for the device' do
    notification.mutable_content = true
    notification.data = { 'hi' => 'mom' }
    expect(notification.as_json['aps']['mutable-content']).to eq 1
    expect(notification.as_json['hi']).to eq 'mom'
  end

  xit 'does not overwrite the content-available flag when setting attributes for the device' do
    notification.content_available = true
    notification.data = { 'hi' => 'mom' }
    expect(notification.as_json['aps']['content-available']).to eq 1
    expect(notification.as_json['hi']).to eq 'mom'
  end

  # redis does not use alert_is_json - unclear if that is a bug or desired behavior
  xit 'does confuse a JSON looking string as JSON if the alert_is_json attribute is not present' do
    notification = described_class.new
    allow(notification).to receive_messages(has_attribute?: false)
    notification.alert = "{\"one\":2}"
    expect(notification.alert).to eq('one' => 2)
  end
end if redis?

redpajama_set_name: RedPajamaGithub


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What do they do when there's no snow? Journalists are obsessed with their snowed up look. Without the snow, they do look less funny 😛 but hey, they are cute with or without the snow. Snow monkey is uniquely Japanese. They NATURALLY go for onsen baths in winter. This is their way to keep warm, well, and to get a red flush of colour for their faces.
We stayed at Shibu onsen. So it was a 45min uphill walk to visit the park. It was a pleasantly serene tar road walk, but steep. I managed it with a pair of flip flops LOL Not recommended by the way. I was just too lazy to change shoes after one too many baths haha.
After the parking lot, the path was no longer easy… rocks, mud and all the other nature goodness. Again, I was still wearing flip flops. They're basic ipanema, in case you're interested, and thankfully did not die out on me. I had them for 4 years already, my travel staple.
Anyways back to the monkeys. They're EVERYWHERE… That's before we arrived at the park. O, the first house that we came across was actually a hotel of sort. They're very firm about non-guests not to use their facilities (fair enough). I was actually more interested in how they manage to get anyone's luggage up or down from that place.
At the ticket gate, there're small coin lockers available. If you have food on you, this is the point to leave and LOCK your food. They're wild monkeys. This park has been around since 1964, they know what they're doing. Leave whatever snacks you have in your bag. It goes without saying, don't touch the monkeys.
The monkeys were surprisingly indifferent to human visitors. No matter what the lens shape / size, these stars of the show seemed to be used to the drill. They even have their own live cam show. It's on 24/7!!
Those baby monkeys were too cute.
It was summer time, so I was really surprised that they still went in for the onsen by themselves… soon, we found out that the park lowers the onsen temperature AND put in some snacks. So of course there were lots of willing monkeys even though it was off season for them.
Around 4.2km from the Yudanaka station (all uphill). Taxi is recommended. direct bus is available in winter only There's an information centre at the Yudanaka train station, you can find out if there's any public transport before taking a taxi.
This particular portrait is taken by my hubby. It is our favourite monkey photo from the trip.
Veronica and I were lucky enough to get to the Snow Monkey park late, with only two other visitors. This was a fantastic experience. It was in late September, no snow in sight.
Thanks for dropping by. It's cool to drop me a link. I visit it right now ???? support fellow bloggers.
Thank you for dropping by ???? yes, flip flops are the ultimate travel staples ????
Wish I had been there Joyce…great post with excellent photos.
Thank you for taking the time to comment, Sue. So sorry for my late response. For some unknown reason, your comment went into the spam box. No idea why that happens, as I'm subscribed to you. Very weird.
I can't believe you trekked around there in FLIP FLOPS!
And yes those monkeys do look like salary men sitting around chatting, lol!
Wonderful story, facts and images Joyce. I am yet to see this mob. The ones at the top of Miyajima are bad enough.
The photos are stunning! The monkeys cannot be cuter, I have actually watched a discovery show about these beauts. It is lovely you actually saw them!
Thank you for reading ???? those photos from discovery channel were amazing.


text:
Q: Remove product add to cart button everywhere I'm trying to remove add to cart button from WooCommerce everywhere and leave it only in single product page
I have made a lot of research and I tried this code but it doesn't work
remove_action( 'woocommerce_after_shop_loop_item', 'woocommerce_template_loop_add_to_cart', 10 );

i want users can only add a product to cart in each single product page

A: Add the follows code snippet in your active theme's functions.php to do that -
add_filter( 'woocommerce_loop_add_to_cart_link', 'remove_add_to_cart_from_all_listing', 99, 3 );
function remove_add_to_cart_from_all_listing( $add_to_cart, $product, $args ){
    if( is_product() ) return $add_to_cart;
    return false;
}

A: if your code doesn't work with the hook then you can do hide by css as well

redpajama_set_name: RedPajamaStackExchange


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You need a shower gift for a special mother-to-be. You can do this. Read this article and make the trip to your local fabric store. Are you worried that you may not be able to complete the baby quilt for the shower is too close in time? Visit my website: www.uniquebabyquiltboutique.com and chose of one unique handmade baby quilts from my collection for your baby shower. Sharon Camp has been quilting for over 30 years.


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In other great Microsoft news, it was announced that the software giant recently completed the acquisition of Metanautix, a data analysis company whose aim is to tear down data silos in order to "connect the 'data supply Read more
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text:
Q: How to use django-sslify to force https on my Django+nginx+gunicorn web app, and rely on Cloudflare's new free SSL? Intro
Cloudflare's providing SSL for free now, and I would be a fool to not take advantage of this on my site, and a downright dickhead to break everything in the process of trying to.
I can code apps just fine, but when it comes to setting up or configuring https/nginx/gunicorn/etc/idon'tknowtheterminology, I know barely enough to follow Googled instructions.
Question
I would like to use django-sslify to force https on my Django web app. How may I achieve this without upsetting the balance in my life, given the following known facts?
Known facts

*

*I'm using Django 1.7, running on a DigitalOcean server hooked up
to a (free) Cloudflare DNS. Django is fitted (served?) with nginx
and gunicorn. Basically followed this guide to get it all set up.

*Accessing my website currently defaults to a regular http://example.com header.

*Manually accessing https://example.com works with
the green lock and all, but this breaks all form submissions with
the error "(403) CSRF verification failed. Request aborted.".

*In my Cloudflare site settings, the domain is currently configured to "Flexible SSL".

*Trying to use django-sslify with my existing setup totally breaks everything, and the browser is unable to return a response.

*This info nugget tells me that I should use the "Full SSL" configuration setting when using django-sslify with Cloudflare's SSL.

*Cause for hesitation found here where it is mentioned that a $20/mo Pro Cloudflare account is needed to handle SSL termination. So I really don't want to screw this up :/

*There was only 1 mention of "http" or "https" anywhere in my nginx and gunicorn configuration, specifically in my nginx config:

location / {
proxy_pass http://127.0.0.1:8001;     ...       }

Ok I think that's all I have
Also, my server is providing an Django Rest Framework api for a Phonegap app, does that need to be taken in to consideration? If I need to provide addtional information do let me know and I'll get back to you. Thank you for taking a look at this! :)

A: CloudFlare allows you to enable specific page rules, one of which is to force SSL (by doing a hard redirect). This is a great thing to use in addition to django-sslify or django-secure

In addition to setting up your SSL redirect, you also need to tell Django to handle secure requests. Luckily, Django provides a decent guide for doing this, but there are a few things that it doesn't mention but I've had to do with nginx.
In your Django settings, you need to tell Django how to detect a secure request
SECURE_PROXY_SSL_HEADER = ('HTTP_X_FORWARDED_PROTOCOL', 'https')

In your nginx configuration you need to set up the X-Forwarded-Protocol header (and the X-Forwarded-For/X-Scheme headers are also useful).
proxy_set_header X-Scheme $scheme;
proxy_set_header X-Forwarded-Protocol $scheme;
proxy_set_header X-Forwarded-For $proxy_add_x_forwarded_for;

You also need to proxy the Host header down, so Django is able to read the correct host and port, which is used in generating absolute urls and CSRF, among other things.
proxy_set_header Host $http_host;

Note that I used the $http_host variable instead of $host or $host:$server_port. This will ensure that Django will still respect CSRF requests on non-standard ports, while still giving you the correct absolute urls.
As with most things related to nginx and gunicorn, YMMV and it gets easier after you do it a few times.


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text:
Home / Medical News / Cara Therapeutics Doses First Patient in Second Pivotal Phase 3 Efficacy Trial of Korsuva (CR845/difelikefalin) Injection in Hemodialysis Patients with Chronic Kidney Disease-Associated Pruritus
Cara Therapeutics Doses First Patient in Second Pivotal Phase 3 Efficacy Trial of Korsuva (CR845/difelikefalin) Injection in Hemodialysis Patients with Chronic Kidney Disease-Associated Pruritus
STAMFORD, Conn., Aug. 07, 2018 (GLOBE NEWSWIRE) — Cara Therapeutics, Inc. (Nasdaq:CARA), a biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pruritus and pain by selectively targeting peripheral kappa opioid receptors, today announced the dosing of the first patient in its second pivotal Phase 3 efficacy trial (KALM™-2) of Korsuva (CR845/difelikefalin) injection in hemodialysis patients suffering from moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP). The global trial is expected to enroll hemodialysis patients in the U.S., Europe and some countries in the Pacific Rim region. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Korsuva injection for this indication, for which there are currently no approved therapies in the U.S. or European Union (EU).
"The initiation of our second Phase 3 efficacy trial in dialysis patients with CKD-aP is an important step toward our goal of developing and commercializing Korsuva injection as a potential novel treatment option for a patient population with significant unmet medical need," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "We will continue to focus on patient enrollment in the coming quarters and expect data readouts from both our U.S. and global Phase 3 trials in 2019."
KALM-2 Phase 3 Trial Design
The Phase 3 international, multicenter, randomized, double-blind, placebo-controlled 12-week treatment trial (with a 52-week open label extension phase) is designed to evaluate the safety and efficacy of 0.5 mcg/kg CR845/difelikefalin injection in 350 hemodialysis patients with moderate-to-severe pruritus.
The primary efficacy endpoint is the proportion of patients achieving at least a 3‑point improvement from baseline with respect to the weekly mean of the daily 24‑hour worst itching intensity numeric rating scale (NRS) score at week 12. In a completed Phase 2 trial, the proportion of patients with an improvement from baseline in the weekly mean worst itching intensity NRS score of ≥3 points at week 8 was statistically significantly higher in the CR845/difelikefalin 0.5 mcg/kg group compared to the placebo group (64% vs. 29%; p1.
Secondary endpoints of the Phase 3 trial include assessment of itch-related quality of life changes measured using validated self-assessment 5-D Itch and Skindex-10 scales as well as the proportion of patients achieving > 4-point improvement from baseline in weekly mean of the daily 24-hour worst itching intensity NRS score at week 12.
About CKD-aP
CKD-aP is an intractable systemic itch condition that occurs with high frequency and intensity in patients with chronic kidney disease undergoing hemodialysis and peritoneal dialysis. Pruritus has also been reported in patients with stage III-V CKD who are not on dialysis. Aggregate, longitudinal, multi-country studies estimate the weighted prevalence of CKD-aP to be approximately 40 percent in patients with end-stage renal disease (ESRD), with approximately 25 percent of patients reporting severe pruritus. The majority of dialysis patients (approximately 60-70 percent) report pruritus, with 30 to 40 percent reporting moderate or severe pruritus.2,3 Recent data from the ITCH National Registry Study showed that among those with pruritus, approximately 59 percent experienced symptoms daily or nearly daily for more than a year. Given its association with CKD/ESRD, most afflicted patients will continue to have symptoms for months or years, with currently employed antipruritic treatments, such as antihistamines and corticosteroids, unable to provide consistent, adequate relief. Moderate-to-severe chronic pruritus has repeatedly been shown to directly decrease quality of life, contribute to symptoms that impair quality of life (such as poor sleep quality), and is associated with depression.4 CKD-aP is also an independent predictor of mortality among hemodialysis patients, mainly related to increased risk of inflammation and infections.
Pisoni RL, et al. Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant. 2006; 21:3495-3505.
Ramakrishnan K, et al. Clinical characteristics and outcomes of end-stage renal disease patients with self-reported pruritus symptoms. International Journal of Nephrology and Renovascular Disease. 2014; 7: 1-12.
Mathur VS, et al. A longitudinal study of Uremic Pruritus in hemodialysis patients. Clin J Am Soc Nephrol. 2010; 5(8):1410-1419.
Cara Therapeutics is a clinical-stage biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pruritus and pain by selectively targeting peripheral kappa opioid receptors (KORs). Cara is developing a novel and proprietary class of product candidates, led by KORSUVA™ (CR845/difelikefalin), a first-in-class KOR agonist that targets the body's peripheral nervous system, as well as certain immune cells. In Phase 2 trials, KORSUVA injection has demonstrated statistically significant reductions in itch intensity and concomitant improvement in quality of life measures in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP), and is currently being investigated in Phase 3 trials in hemodialysis patients with CKD-aP. Additionally, in a recently completed Phase 2/3 trial in post-operative patients, I.V. CR845/difelikefalin has demonstrated reduction in moderate-to-severe pain, while also reducing the incidence and intensity of nausea and vomiting throughout the post-operative period.
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Examples of these forward-looking statements include statements concerning the expected enrollment of the CR845/difelikefalin injection Phase 3 pivotal efficacy trials; the timing of data readouts for CR845/difelikefalin injection clinical trials; the ability of the clinical trials to demonstrate an extended patient benefit; and the potential for CR845/difelikefalin injection to be a therapeutic option for CKD-aP. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Cara Therapeutics' filings with the Securities and Exchange Commission, including the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2016 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Cara Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Posted: August 2018
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In this section: Investigational Device Exemption (IDE)
Investigational Device Exemption (IDE)
IDE Tracking Improvements
IDE Approval Process
IDE Definitions and Acronyms
IDE Responsibilities
IDE Application
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IDE Records
IDE Institutional Review Boards (IRB)
IDE Informed Consent
IDE Financial Disclosure
Early Feasibility Studies (EFS) Program
Expanded Access for Medical Devices
Acceptance of Data from Clinical Investigations for Medical Devices
IDE Enforcement of Good Clinical Practices (GCP) Regulations
Import and Export of Investigational Devices
FAQs about Investigational Device Exemption
IDE Related Topics
IDE Guidance
IDE Regulations
IDE Links
Device Advice: Comprehensive Regulatory Assistance
How to Study and Market Your Device
Premarket Submissions: Selecting and Preparing the Correct Submission
Clinical Investigator
Early Collaboration
FDA Contacts
Foreign Companies/Studies
In Vitro Diagnostic Devices
New Indication for Marketed Device
Promotion of Investigational Devices
Significant/Nonsignificant Risk
Statistical Guidance
Study Sites
If my device has been approved and marketed in a foreign country and I am conducting clinical trials in the U.S., should I report an adverse event from the U.S. trial under the IDE program or the Medical Device Reporting (MDR) program?
If your device is not marketed in the U.S., you should report an adverse event under the IDE program (812.150). The sponsor must report the results of an evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBs and investigators within 10 working days after the sponsor first receives notice of the adverse effect.
If the adverse event occurs in a foreign country in which it is legally marketed and not under the control of a clinical study, the adverse event should be discussed in the IDE progress report since the adverse information may affect risk analysis.
The adverse event should not be reported under the MDR program because the MDR program only applies to medical devices that are legally marketed in the U.S.
My device is marketed in the U.S. I am conducting a clinical trial in the U.S. for the same device, but for a different indication for use, should I report an adverse event under the IDE program or the MDR program?
Adverse events that occur in subjects enrolled in the clinical trial should be reported under the IDE program (812.150). The sponsor must report the results of an evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBs and investigators within 10 working days after the sponsor first receives notice of the adverse effect.
Adverse events that occur in the U.S. but outside of the clinical trial would be reported through MDR; however, the adverse event should be discussed in the IDE progress report since the adverse information may affect risk analysis.
Can a clinical investigator submit an IDE?
Yes, a clinical investigator can sponsor his/her own study in which case they are considered a sponsor-investigator and must comply with all the responsibilities of both the sponsor and investigator.
Does the clinical investigator need to sign form FDA-1572?
No, this is a form used for drug studies. For device studies, the sponsor should develop an investigators agreement which includes the elements of 21 CFR 812.43(c). The sponsor should have all investigators sign the agreement prior to participating in the study.
Are IDE records released to the public?
FDA will not disclose the existence of an IDE unless:
FDA determines that the information had been previously disclosed to the public;
FDA approves a PMA for a device subject to an IDE; or
a notice of completion of a Product Development Protocol (PDP) is in effect.
If the existence of an IDE file has not been publicly disclosed or acknowledged, no data or information in the file are available for public disclosure except for information on banned devices and a report of an adverse effect to an individual on whom an investigational device has been used. [(§812.38)]
Data or information contained in the file is not available for public disclosure before approval of an application for PMA or the effective date of a notice of completion of a PDP. Upon approval FDA will release a summary of the safety and effectiveness data on which the decision was based. Other disclosable information available after the device has been approved includes any protocol for a test or study, adverse reaction reports, and correspondence after confidential information has been deleted. Information available for public disclosure is outlined in 21 CFR 814 Premarket Approval of Medical Devices section §814.9.
Can I receive advice from FDA on non-clinical testing and/or on my clinical protocol?
Yes. There are numerous guidance documents available from FDA that provide recommendations on the non-clinical and clinical testing of specific device types. Additionally, FDA accepts Pre-Submissions, in which you can submit information to FDA and receive advice on topics such as a non-clinical testing plan and/or a draft clinical protocol. Additional information on Pre-Submissions may be found in the FDA guidance "Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program." FDA's guidance represents FDA's approach to this topic.
Additionally, there are two types of early collaboration meetings available that are discussed in the FDA guidance "Early Collaboration Meetings Under the FDA Modernization Act (FDAMA)". These formal interactions (Determination Meetings and Agreement Meetings) are specific to clinical investigations and do not address non-clinical testing or protocols.
I have questions about the IDE regulations. Who should I contact at CDRH?
For comprehensive regulatory education about medical devices and radiation-emitting products, please see Device Advice and CDRH Learn. Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
For questions about devices regulated by the Center for Biologics Evaluation and Research (CBER), contact CBER's Office of Communication, Outreach and Development (OCOD) at either 1-800-835-4709 or Industry.Biologics@fda.hhs.gov
Can a foreign company submit an IDE/Is a U.S. Sponsor required?
A foreign company cannot sponsor an IDE; the company must have a U.S. agent who acts as the sponsor (see 21 CFR 812.18(a)). The U.S. agent must fulfill all the responsibilities of a sponsor identified in the IDE regulations.
Do clinical studies have to be conducted in the U.S. / Will foreign studies be accepted?
The FDA continues to promote global harmonization in many aspects of medical device development and regulation, including our commitment to recognize the value of and accept, where appropriate, data from multiple sources and countries.
For more information regarding the FDA's acceptance of clinical data refer to our page on Acceptance of Data from Clinical Investigations for Medical Devices and the FDA guidance entitled "FDA Acceptance of Clinical Data to Support Medical Device Applications and Submissions Frequently Asked Questions.".
Do the IDE regulations apply to in vitro diagnostic devices?
Many in vitro diagnostic (IVD) devices are exempt from the IDE regulations. Under section §812.2(c) of the IDE regulations, studies exempt from the IDE regulations include diagnostic devices if the testing:
is noninvasive;
does not require an invasive sampling procedure that presents significant risk;
does not by design or intention introduce energy into a subject; and
is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure;
IVD devices that are under study, including IVD devices that are exempt from the IDE regulations, must comply with labeling requirements under 21 CFR 809.10(c)(2). One of two statements is required, as applicable for each case: "For Research Use Only. Not for use in diagnostic procedures", or "For Investigational Use Only. The performance characteristics of this product have not been established."
Studies which are exempt from the requirements of the IDE regulations are not exempt from the requirements for IRB review and approval under Part 56 and the requirements for obtaining informed consent under Part 50. In addition, IDE exempt studies are not exempt from §812.119, Disqualification of a clinical investigator.
For guidance regarding the applicability of these regulations with respect to investigations being conducted under the provisions of §812.2(c), contact the reviewing IRB and/or the CDRH IDE Staff at 301-796-5640 or CBER's OCOD at 301-827-1800 .
Additional guidance for in vitro diagnostic device studies can be found in the guidance "In Vitro Diagnostic (IVD) Device Studies – Frequently Asked Questions."
Where can I find an IRB?
The institutions where the study is to be conducted should be contacted to determine if they have their own IRB. If the study is conducted at a site that does not have its own IRB, the investigators should be queried to see if they are affiliated with an institution with an IRB that would be willing to act as the IRB for that site in the study. There are also independent/contract IRBs that can be contracted to act as the IRB for a site. Additionally, an IRB reviewing and approving IDE investigations should comply with the requirement of 21 CFR Part 56. Additional information on IRBs is available in the FDA Information Sheets.
Are there special labeling requirements for investigational devices?
Yes. Under § 812.5 an investigational device or its immediate package must bear a label with the following information:
the name and place of business of the manufacturer, packer, or distributor;
the quantity of contents, if appropriate; and
the statement, "CAUTION  Investigational device. Limited by Federal (or United States) law to investigational use."
The label must also describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions.
The labeling of an investigational device must not contain any false or misleading statements nor imply that the device is safe or effective for the purposes being investigated.
If the investigational device is used solely for research on laboratory animals, the label must contain the following statement: "CAUTION  Device for investigational use in laboratory animals or other tests that do not involve human subjects."
The sponsor should provide detailed information on device labeling in the investigational plan. This information may vary depending on the device and the nature of the study. Product labeling should be sufficient to ensure stability of the test article for the duration of the study (storage requirements, calibration procedures), bear sufficient directions for proper administration, and detail procedures to follow in the event of patient injury.
Do IDE regulations apply if the device has already been approved for a different indication for use?
Yes, the clinical study of a new indication for an already marketed device falls under the IDE regulations.
Can I advertise my investigational device? What other restrictions apply?
Under § 812.7, a sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator cannot:
Promote or test market an investigational device, until after FDA has approved the device for commercial distribution.
Commercialize an investigational device by charging the subjects or investigators a higher price than that necessary to recover costs of manufacture, research, development, and handling.
Unduly prolong an investigation. If data developed by the investigation indicate that premarket approval (PMA) cannot be justified, the sponsor must promptly terminate the investigation.
Represent that an investigational device is safe or effective.
However, the sponsor may advertise for research subjects to solicit their participation in a study. Appropriate advertising methods include but are not necessarily limited to: newspaper, radio, TV, bulletin boards, posters, and flyers that are intended for prospective subjects.
Advertisements should be reviewed and approved by the IRB to assure that they are not unduly coercive and do not promise a certainty of cure beyond what is outlined in the consent and the protocol. No claims should be made, either explicitly or implicitly, that the device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other device.
FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection processes.
Additional guidance is available in the following guidance documents:
"IRB Information Sheets - Recruiting for Study Subjects".
Preparing Notices of Availability of Investigational Medical Devices and for Recruiting Study Subjects
Will insurance cover treatment with an investigational device?
For patients with Medicare, the Centers for Medicare and Medicaid Services (CMS) determines whether costs associated with routine care and the investigational devices are covered. To support this determination, the FDA categorizes IDE-approved devices based on whether available data demonstrates that initial questions of safety and effectiveness have been resolved. IDE-approved devices are assigned to one of two categories:
Category A - Experimental
Category B - Non Experimental/Investigational
The FDA communicates the assigned category in a formal letter sent to the study sponsor. The sponsor submits the letter to CMS, which considers the FDA-assigned category and other factors to determine whether or not a device meets the requirements for Medicare coverage. The background and criteria associated with the FDA's categorization process is described in the guidance document titled, "FDA Categorization of IDE Devices to Assist CMS with Coverage Decisions."
For an IDE-approved device assigned to Category A, CMS may cover only routine care items and services, but not the cost of the device itself. For an IDE-approved device assigned to Category B, CMS may cover routine care items and services as well as the cost of the investigational device if specific criteria are met. If the criteria are not met for a Category B device, neither the device nor other elements of the study are covered by Medicare. To review the criteria and process for requesting coverage for an IDE, the IDE sponsor may refer to their website (Medicare Coverage Related to Investigational Device Exemption (IDE) Studies).
Is my study significant risk or nonsignificant risk?
FDA has a guidance document to help explain how to determine whether a device study is significant or nonsignificant risk. If the sponsor believes a device study is nonsignificant risk, the sponsor can provide information to the IRBs reviewing the study explaining why the device study does not pose a significant risk. If the IRBs agree and approve the study, the research may be conducted and FDA does not need to be notified. However, if an IRB determines the study is significant risk, the sponsor must notify FDA in writing (21 CFR 812.150(b)(9)). The study may not begin until FDA approves the study or provides a determination that the investigation is nonsignificant risk.
How many subjects and sites do I have to include in the study?
The number of subjects and sites to include in a study depends on the study objectives and the study design needed to result in a scientifically valid conclusion.
It is recommended that more than one site be included to provide assurance that study results are reproducible.
FDA has developed several guidance documents that address statistics for clinical trials.
Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests
Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials
I am a patient. Where can I find a clinical study that will help me?
There is no centralized repository for information on device clinical trials. Your health care provider may be able to provide information. Hospitals associated with medical schools are often involved in research and institutions that are participating in clinical trials will sometimes place advertisements in newspapers or magazines to recruit subjects.
At this time, FDA does not maintain a clinical trials database for medical devices and our regulations do not permit us to release information regarding investigational devices. However, the National Institutes of Health maintains a clinical trials database for trials that they support. It may be accessed through the Internet at ClinicalTrials.gov. Please remember that participating in a clinical trial may or may not help you. The safety and effectiveness of an investigational device is not known.
Can the sponsor get a waiver from certain IDE requirements?
Under § 812.10, a sponsor may request FDA to waive any requirement of the IDE regulations. A waiver request with supporting documentation may be submitted as part of an application or separately. FDA may grant a waiver of any requirement that is not required by the FD&C Act and that is unnecessary to protect the human subject by providing a letter to the sponsor outlining the waiver.
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