Tag: FDA

Abilify connected pill: ethics and privacy aspects of Personal Health Monitoring

ABILIFY MYCITE: A FIRST FDA APPROVAL FOR mHEALTH AND CONNECTED MEDICAL DEVICES

On 13 November 2017, we have probably reached a historical new step in digital health (and mHealth) with this market approval from the FDA for “Abilify MyCite“, the first digital tracking-pill which sends data to your doctor. This connected pill is used to track whether patients sufferring from schizophrenia, bipolar I disorder, and depression have taken their medication, which is used for Personal Health Monitoring (‘PHM‘).

As mentionned by Pharmacytimes:

“the approval of the pill and the sensor together represents a first for the FDA“

even if the sensor itself that is used along with aripiprazole (substance used for patient suffering from schizophrenia) was first cleared for use by the FDA in 2012. As secondary or side effects, the clinical trials revealed adverse events such as nausea, vomiting, constipation, headache, dizziness, uncontrollable limb and body movements (akathisia), anxiety, insomnia, and restlessness. However, the common adverse events associated with the sensor were related to the patch, and were predominantly skin irritation.

Find more information on the website of the FDA.

________________________________

TECHNOLOGY AND FUNCTIONALITIES – How it works

On the technology side, the sensor embedded into the Ability MyCite pill syncs with a smartphone and sends an alert to the patient’s smartphone. The doctor receives also a notification through the App when the medication is ingested via a patch that is worn on the surface of the skin of the patient. If the patient shares its data with his practitioner, the latter has the ability to monitor whether the patient has ingested properly. According to the US TV channel PBS, researchers are also trying to manufacture ePills that collect and process other body-related data by monitoring internal heat of the body for several days long.

________________________________

TECHNICAL ASPECTS OF THE DEVICE

According to LiveScience, the technical aspects are as follows:

“It’s a partial power source, “the patient becomes the battery”. The pill integrates a silicon chip with a logic circuit and contains copper and magnesium.  The chip’s logic circuit makes a small modulated current — a graph of the current levels would look like a sine wave. Since the human body is conductive, the wearable sensor can pick up the changes. The modulated current can encode ones and zeroes, similar to an FM signal. “It works in a similar way as an EKG,” or electrocardiogram. These machines pick up on changes in electrical current in the body to monitor heartbeats. The wearable sensor does the same thing, though the current is smaller.” The pill is designed to work for only about 3 minutes. That’s just enough time for it to send a signal to the wearable sensor that it should wake up and start gathering data. That saves battery power and allows the wearable sensor to work for a week at a time.

The patch and sensor is manufactured by the company Proteus Digital Health and aripiprazole marketed by Otsuka Pharmaceutical.

________________________________

ETHICS AND LEGAL ISSUES

PATIENT MONITORING AND REDUCING HEALTH COSTS

Personal Health Monitoring (‘PHM ‘) contains at least two major advantages.

MEDICAL COMPLIANCE – being the “consistency and accuracy with which someone follows the regimen prescribed by a physician or other health professional“. In the context of mental disability, the physician must ensure that the patient suffering from a mental disorder takes the prescribed medication on a regular basis. This may be particularly interesting for patients who may find themselves incapable of making a proper judgement (such as elder people). In the USA, a study from the National center for biotechnology information showed that “an estimated 50% of those who respond well to medications are nonadherent to their treatment regime“. Therefore, medical compliance is also a important challenge for patients who are suffering from a mental illness; and

HEALTHCARE COSTS – which could be reduced if more patients would take their pill properly. Consequences are both medical and financial. When a patient do not or, forgets to, take a pill, or do not follow the treatment as prescribed, his/her health may be worsened and this person may require treatment adjustment, more medicine, another hospitalisation or even a further surgery should there be a need to. In particular, this article indicates that the “loss that the taxpayer incurs when patients fail to take their medication, the cost of which is assumed to be at least $100 billion. According to an American report, these numbers could even be between $100 et $300 billion.

*  *  *
TECHNOLOGICAL ADVANCEMENT: YES.  BUT AT WHAT COST AND
TO WHAT EXTENT DOES THIS REMAIN A PROGRESS?

Although such technological advancement (connected pill to track patient’s medical compliance) is remarkable for healthcare costs reduction, not everybody agrees to it, especially within the medical profession. Moreover, it is legitimate to ask to what extent such technology can constitute a practical improvement, not just a scientific progress.

What value does this progress add for patients, the healthcare system and the society in general? What does it improve, is it better than before? If yes, how and what are the bad sides of it? What is the balance between the bad and good sides of this? Will the benefits for the patient override financial benefits?

Some people already rose their voice and expressed reluctance to Personal Health Monitoring (‘PHM’), which scientists have already looked into and published on this complex topic. (see additional notes on that topic at the end of this article).

Altough a few have called this practice “medical Big Brother (or biomedical Big Brother according to the New York Times), PHM raises a number of ethical questions, which can lead to at least 8 key  points and interrogations:

1. Privacy – for personal health monitoring, two types of privacy aspects can emerge, which are personal privacy and data privacy. This also relates to risk of interference in the private life of the patient by collecting and processing health (sensitive or even biometric) patient data. Is such data processing in compliance with explicit consent of the patient, who may not able to make a proper judgement?  This article describes very well some privacy aspects  that personal health monitoring are raising.

2. Visibility or  obstrusiveness – Visibility appears to refer to “the degree to which a PHM device is noticeable by the user and other individuals, both at home and in public“. In accepting the use of tracking devices for dementia patients, cognitively intact older adults identified ease of use, size and weight as important in accepting a tracking technology. One consider the patient differently, being seen as an ill human being. This may create a risk of discrimination by the society and the person might be more vulnerable;

3. (over)Medicalization – the devices have the effect of reminding the user or occupants of a medical condition in a non-medical environment. The home could be turned into a medical environment or “de facto intensive care unit” as well as creating stigmatization linked to the fact that the person feels under surveillance;

4. Social isolation – the patient monitored will reduce or cease going to the hospital or to see the physician for regular check-ups. Therefore, this could increase patient’s loneliness and social isolation with psychological and medical consequences with a lack of motivation and reduction of the mentality;

5. Autonomy – what room remains to the patient with PHM to decide how to take the pill or not? What if the patient wishes to stop taking the pill, for good reasons? Where are we talking about pressure on the patient will?

6. Shame et identity – what consequences could there be on the personality of the patient, who may be perceived by the society as marginal human being, in particular when the treatment is visible?

7. Providing healthcare – with remote care, to what extent does this improve or reduce its effectiveness, especially when the patient does not move him/herself anymore? Is this an efficient manner to treat a patient, shall this remain the exclusive way of doing it or should we combine it with physical appointments?

8. Security and reliability of the technology. This element is obviously central for both privacy and health reasons.

Do these aspects reduce or delete the patient’s responsibility or does it create an over-responsibility? With or without benefits?

How about from an insurance point of view if the patient do not takes the pill while he/she is being monitored with or without worsening of his/her health? Suspension, reduction, cessation of the payment by the insurance or the medical measures? To what extent can the insurance have access to such information or personal health-related data?

________________________________

A PRIVACY PERSPECTIVE?

As this article pointed out, despite huge costs reductions (around 100 billion) and health benefits of this mHealth technology for the healthcare system and patients, patient’s privacy is an area of concern which is even more related to medtech technologies with Big data and IoT (Internet of Things) in the healthcare sector. Combined with the patch worn by the patient, the sensors that are embedded into the pill may provide far more data about the patient than just taking a pill or not.  The device may be used in a way to gather data from the patient’s body, such as the heart rate, how much the patient sleeps, how fit the patient is, etc.

The major concern is the misuse of such sensitive data, which could be used by corporations or government to collect more personal and biometric information about citizens that they had consented to revealing. Furthermore, since the technology has only recently come into the public domain, very few regulations exist to police it, says this article. Misuse for marketing purposes, is one thing. Data breach, criminal intents, or cyberattack on the device itself are another thing with severe consequences for both patients’ health, privacy and reputations of tech and pharma organizations. Further, another study explains that it appears impossible to obtain informed consent from recipients of PHM because full understanding of the implications of using PHM cannot be gained without actually using the technology. Therefore, using the technology without informed consent, may be considered as illegal processing, which creates a vicious circle. This article suggests that piloting methods such as storytelling and prototyping may present a possible solution to this problem and avoid collecting personal data without the proper legal basis for processing.

________________________________

PRIVACY AND INFORMATION SECURITY 

From an EU and Swiss perspective, health-related data (health or biometric) is considered as a special category of personal data that we call “sensitive data“, where the processing is generally prohibited, unless the controller can demonstrate a legal ground for the processing, such as the patient’s explicit consent (art. 9 §2 (a) GDPR, art. 4 al. 5 and 13 al. 1 of the Swiss DPA), the provision of medical services by a health professional tied by a secrecy obligation (art. 9 §2 (h) and 9 §3 of the GDPR) or private overriding interests (art. 13 al. 2 of the Swiss DPA). As one can read in the press almost everyday now, cyberattacks can happen, and a data breach may lead authorities to impose hefty fines, with 4% of worldwide annual turnover according to article 83 of the GDPR, although fines should remain a last resort in the sanction mechanism applied by the authorities. I wrote a note in this article about the envisaged approach with fines and sanction pursuant to the GDPR.

In addition, the doctor would also have to require the patient’s prior explicit consent before sharing, or allowing any third party to access, any sensitive data . See my previous note on recommendations for outsourcing in the context of medical billing for healthcare professionnals.

There are many other obligations under these regulations, which this article does not intend to cover.

________________________________

CONCLUSION

This FDA approval sounds like a very good “signal” to pharmaceutical companies developing connected drugs and advanced digital life science technologies, mHealth and medical devices.  This can improve the life of many patients, while saving costs and improving efficiencies in the treatment.

There is no need for scaremongering. However, remaining careful using the device for the purpose of the treatment, informing the patient and gathering explicit consent, processing only the data that is necessary for the purpose of the treatment, working with ethics and respect for the individual, especially if these patients have a reduced of discernment, are some good steps to ensure the individual’s privacy.

_____________________

To read more on this topic:

  • Mittelstadt, Brent, Ben Fairweather, Mark Shaw and Neil McBride. “The Ethical Implications of Personal Health Monitoring.” IJT 5.2 (2014): 37-60.Web.4Feb.2018.doi:10.4018/ijt.2014070104.
  • Mittelstadt, B., Fairweather, N.B., McBride, N., Shaw, M., 2011. Ethical Issues of Personal Health Monitoring: A Literature Review, in: ETHICOMP 2011 Conference Proceedings, ETHICOMP 2011, Sheffield, UK.
  • Elin Palm, Anders Nordgren, Marcel Verweij and Göran Collste, Ethically Sound Technology? Guidelines for Interactive Ethical Assessment of Personal Health Monitoring, 2013, Interdisciplinary Assessment of Personal Health Monitoring, 105-114.
  • Nordgren, Anders. (2013). Privacy by Design in Personal Health Monitoring. Health care analysis : HCA : journal of health philosophy and policy. 23. . 10.1007/s10728-013-0262-3.
  • Data protection and privacy in connected health, an article from a blog for research and innovation relating to emerging technologies.
  • Information notice  from “Otsuka Pharmaceutical”, the manufacturer of Abilify Mycite.

—

By Gabriel Avigdor | NTIC.ch

Prescription support software are considered as medical device

Prescription support software is considered as medical device

On 7 December 2017, the European Court of Justice (‘ECJ’) made an important ruling in the French case SNITEM and Philips vs Premier Ministre des Affaires sociales et de la Santé (Case C-329/16). The Court followed its general advocate advice, who issued a non-binding recommendation on 28 June 2017, and defined for the first time under what conditions should medical software (standalone software) be qualified as a medical device pursuant to Directive 93/42/EEC on medical device.

In this decision, the ECJ considers that “software, of which at least one of the functions makes it possible to use patient-specific data for the purposes, inter alia, of detecting contraindications, drug interactions and excessive doses, is, in respect of that function, a medical device within the meaning of those provisions, even if that software does not act directly in or on the human body”. Therefore, software of which specific functions do not have a medical purpose, are not medical device and are out of the scope of the Directive.

__________________

CE marking is sufficient

The Court adds that once the software bears CE marking, a national authority cannot request the software developer to proceed to an additional requirement such as another certification, as CE marking is sufficient.

In this French case, a decree contained an obligation to get a specific certification for prescription support software according to art. L. 161-38 of the French Code of Social Security. The French authority maintained its position that such software cannot be considered as medical device and therefore, would require this specific certification. WRONG, says the ECJ who confirmed that the clear intention of Philips to use this software in the context of healthcare, and for medical use, makes the functions of this software a medical device. Certications issued by the “Haute Autorité de Santé” (‘HAS’) were compulsory and now are now anymore. Even more, the decree will certainly be either cancelled or amended after this ruling.

This is an important decision for the medical software industry and for innovation in that sector to place them on the EU market (and also in Switzerland), as ECJ clarifies that although it remains compulsorily to “bear the CE marking of conformity when it is placed on the market. Once the marking has been obtained, the product, having regard to that function, may be placed on the market and circulate freely in the European Union without having to undergo any additional procedure, such as a new certification”.

This EU ruling is a lightening in the process which will benefit the industry by save time and money when putting medical software on the market. This clarification allows companies to avoid engaging costs as compliance as a measure of prevention. Legally speaking, there may be a possibility for companies that are in the process of getting their medical software certified to stop the process, or even claim for reimbursement if the decree is cancelled or modified and becomes illegal as a result of the ECJ ruling. In addition, it is likely that this decision may have an impact in other Member States of the EU, which would also be transposable, not only for prescription support software, but also for other medical software, or mobile medical Apps.

__________________

Scope of this decision

What is the scope of this decision?

Firstly, this decision applies clearly to prescription support software, but not only. The the ECJ provided criteria that are broad enough for applying to other medical software if the objective pursues a specifically medical objective. This ruling may be applicable by analogy to all medical software with a medical objective, even with no interaction in or on the human body. It is however necessary to proceed to a specific analysis on a case by case basis for each functionality of the medical software or the mobile medical App.

Secondly, this decision also applies to hospitals developing medical software, as these institutions can be software developers even with no commercialisation, as though they are responsible for first placing on the market. It is therefore necessary for hospitals developing medical software or Apps to assess whether it requires complying with the EU medical device Directive.

From a geographic point of view, even if the decision comes from a European authority, it applies to Switzerland, with automatic recognition of CE marking thank to the international convention on mutual recognition in relation to conformity assessment dated 2002 with EU.

Finally, the fact that this ruling is based on the Directive 93/42/EEC will remain valid with its replacement by the EU Regulation 2017/745 on medical device that is going to replace as of 26 May 2020.

__________________

In deeper details – Background of the dispute

The dispute arose in relation to “Intellispace Critical Care and Anesthesia” (“ICCA”) software developed by Philips, as this company focuses now into the software and IT projects in relation to the healthcare sector. The functions of the prescription support software makes it possible to use patient-specific data for the purposes, inter alia, of detecting contraindications, drug interactions and excessive doses.

The dispute opposed the national syndicate of medical technological industries (SNITEM in French) and Philips on one hand, against the French Minister of Social and Health Affairs on the other hand. Based on a local decree which imposes prescription support software companies to get a specific certification, the French authority argued that: (a) Philips’ software was not a medical device, (b) requires getting the additional specific certification for prescription support software, and therefore (c) cannot freely put into the market its software on the sole basis of the CE marking.

On the other hand, Philips argued that, its software is a medical device and “the requirement to adapt software to technical standards constitutes a measure having equivalent effect to quantitative restrictions on imports which, overlapping with the certification obligation for medical devices laid down in Directive 93/42, which is applicable to software, does not meet the requirements of necessity and proportionality”.

In other words, Philips claimed that CE marking was sufficient. Philips won the case on this question.

__________________

Challenges of this case and first precedent

The central question of this case is not the certification itself, but the question to know if ICCA software is be considered as a medical device or not in accordance with Directive 93/42/EEC on medical device. This question may appear somehow unoriginal. It is not. If a software is considered as a medical device, regardless of how it is classified, will need to comply with the EU medical device Directive requirements. In the German case Brain Products GmbH vs BioSemi VOF, the ECJ only provided an indirect reference to the criteria for software as a medical device (‘SaaMD’) qualification.  In that case, the ECJ mentioned that fitness Apps would probably not meet the definition of medical device, while software monitoring humain brain activity would.

The Philips case also refers to the MEDDEV 2.1/6 (Commission Guidelines on the qualification and classification of stand-alone software used in healthcare within the regulatory framework of medical devices) as explained by the advocate general in its recommendations dated 28 June 2017.

__________________

CONDITIONS AND EXAMPLES

ECJ reminds that it is not sufficient to use the software in a medical context; it is also necessary that the intended purpose, defined by the manufacturer, is specifically medical. Therefore, two cumulative conditions are necessary to consider a health-related software as a medical device, which are relating respectively to the objective pursued and the action resulting therefrom.

  1. Objective pursued: a medical device must be intended by the manufacturer for use in humans for the purposes, in particular, of the diagnosis, prevention, monitoring, treatment or alleviation of a disease, and the diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap;
  2. Action resulting therefrom: ECJ interprets the Directive 93/42/EEC and considers that “although that provision provides that the main action of the medical device ‘in or on the human body’ cannot be obtained exclusively by pharmacological or immunological means, or by metabolism, it does not require such a device to act directly in or on the human body”.

Interesting to notice that, according to the ECJ’s argumentation, the second condition is not decisive. On the contrary, requiring that the action resulting from the device shall produce an effect or works directly in or on the body would mean that software with no effect on the body would not be subject to the Directive, which would be contrary to the intent of the EU legislature.

In the case of prescription support software, the European Court of Justice states (§25) that functions of such software: “that cross-references patient-specific data with the drugs that the doctor is contemplating prescribing, and is thus able to provide the doctor, in an automated manner, with an analysis intended to detect, in particular, possible contraindications, drug interactions and excessive dosages, is used for the purpose of prevention, monitoring, treatment or alleviation of a disease, and therefore pursues a specifically medical objective, making it a medical device within the meaning of Article 1(2)(a) of Directive 93/42”.

SaaMD or not? Examples:

The ECJ provides examples of prescription support software that may or may not be used as a medical device:

  • SaaMD: function that permits the use of data specific to a patient to help his doctor issue his prescription, in particular by detecting contraindications, drug interactions and excessive doses, even though it does not itself act in or on the human body;
  • Not a SaaMD: software for general purposes, when used in a healthcare setting, is not a medical device;
  • Not a SaaMD: software intended to indicate the contraindications mentioned by the manufacturer of that drug in its instructions for use;
  • Not a SaaMD: software that, while intended for use in a medical context, has the sole purpose of archiving, collecting and transmitting data, like patient medical data storage software, the function of which is limited to indicating to the doctor providing treatment the name of the generic drug associated with the one he plans to prescribe.

__________________

OUTCOME OF THIS RULING

After this ruling, there are at least three main take aways:

  • First, medical device regulation applies to functionalities of medical software where two cumulative conditions are met (medical purpose pursued by the manufacturer and the action pursued therefrom), with a focus on the first condition;
  • Second, such regulation only applies to functions of the software which are coded in a way to produce such effect, but do not apply to the source code in its entirety, even if the software has no effect in or on the human body;
  • Third, where the software, for that particular section of the source code, bears CE marking, it benefits from freedom of circulation of goods within the EU [and therefore in Switzerland as well] and can be placed on the market without any further certification or requirement.

__________________

What other consequences for software as a medical device?

When a software is qualified as a medical device, the manufacturer will have to assess its classification based on the degree of risk for the human body (classes from I to III) and will have to comply with its duties to declare Class I software to the regulation authority (national authorities in the EU and Swissmedic in Switzerland). For classes IIa, IIb and class III software, obligations are stricter.

Depending on the conditions that are applicable, there is a materiovigilance requirement (pre-market approval and then post-market surveillance/vigilance) by the manufacturer, as well as product security, quality control and quality assurance management, as well as other standards (such as ISO). For products coming from the EU, once they bear the CE marking, they benefit from the freedom of circulation in Switzerland and vice versa without any pre-market approval.

All standards that apply to medical devices, depending on the degree of risk, but also obligations, restrictions and potential sanctions of the authorities, will mutatis mutandis apply to software as a medical device. This is necessary to guarantee free circulation within the EU of safe and secure products for consumers or patient health.

Want to know more?