Global Health Journal 5 (2021) 183–189

Contents lists available at ScienceDirect

Global Health Journal

journal homepage: https://www.keaipublishing.com/en/journals/global-health-journal/

REVIEW

A review on emerging smart technological innovations in healthcare sector

for increasing patient’s medication adherence
Pankaj Pal a, Sharda Sambhakar a, Vivek Dave b,∗, Shailendra Kumar Paliwal c, Sarvesh Paliwal a,
Monika Sharma d, Aadesh Kumar e, Nidhi Dhama e
a Department of Pharmacy, Banasthali University, P.O. Banasthali Vidyapith, Distt. Tonk, Rajasthan 304022, India
b
Department of Pharmacy, School of Health Sciences, Central University of South Bihar, SH-7, Gaya - Panchanour Road, P.O.- Fatehpur, P.S. Tekari, Gaya 824236,
India
c
Department of Pharmacy, Lala Lajpat Rai Memorial Medical College, Garh Road, Meerut 250001, India
d
ABBOTT Healthcare Private Limited, Village Bhatauli Khurd, Sai Road, Baddi, Himachal Pradesh 173205, India
e
Department of Pharmaceutical Chemistry, Kharvel Subharti college of Pharmacy, Swami Vivekanand Subharti University, Subhartipuram, NH-58, Delhi-Haridwar
Bypass Road, Meerut 250005, India

a r t i c l e i n f o a b s t r a c t
Article history: In this paper, we reviewed the various advanced technologies and methods that could help patients for measuring
Received 4 June 2021 adherence of patients. There exist intelligent technologies that are available for measuring medication adherence,
Received in revised form 8 October 2021
including medication event monitoring system (MEMS®), smart blister packs, radio frequency identification
Accepted 24 November 2021
(RFID) embedded smart drawers, and wisely aware RFID dosage (WARD) system. Utilization of these advanced
Available online 25 November 2021
technologies and systems have aided in enhancing the adherence to a greater extent. For example, MEMS® refers
Keywords: to the electronic cap that counts the number of bottles opened, but it can be employed only with bottles. Smart
Radio frequency identification (RFID) blisters are pharmaceutical packagings that possess the capability of monitoring when a pill or tablet is taken out
mHealth
of its packing. All those intelligent technologies can help in active monitoring of patients regarding adherence
Smart blister
and capable of eradicating various medication errors due to which adherence is affected.
Smart drawer
Wisely aware RFID dosage (WARD) system
iCabiNET

1. Introduction The expansion of printable electronics has enabled various researchers

to make use of its employability in smart packaging, attributed to its
Poor or inadequate adherence to prescribed regimens cause nega- flexibility and low cost. Considering smart packaging, printed electron-
tive effects on health and economic status of an individual.1-2 Various ics can be employed for product authentication, active monitoring of
studies have demonstrated that up to 50% of patients do not adhere to patients, inventory management and active branding.7 The addition of
the prescribed medications which will ultimately results in relapse and real-time functionalities in packaging can add a real value to the pack-
rehospitalization, enhanced drug wastage through excessive dosage, en- aging, which was previously seen as merely a disposable pack.
hanced resistance to drugs and make it more challenging for the physi- A variety of methods have been evaluated to improve adherence, in-
cians to assess effectiveness of the treatment. Although World Health Or- cluded financial incentives to patients,8 labor intensive intervention,9-10
ganization (WHO) believes that enhancing adherence rates can deliver and information technologies regarding health (such as smart drug pack-
more health benefits than refining particular treatments.3 In the United aging, automated dispensers and feedback systems).11-13 Smart pack-
States (U.S.), approximately 50% of hospital admissions occurred due aging technology possess many forms, with some integrated features
to poor or inadequate medication adherence, causing annual costs of such as condition monitoring, event recording, feedback mechanisms,
over USD 100 billion and deaths of approximately 125 000 people.3-6 reminder systems, status displays and anti-counterfeiting technology.14
From the above stated facts it clear that why inadequate or poor medi- These features are integrated with intervention programs that have been
cation adherence has been considered as an drug problem in the U.S.1 In proved to be the most consistent in improving the adherence. Besides
global pharmaceutical market the smart packaging holds significant im- these merits, the smart packaging technology possesses limitations like
portance because of its employability in patient’s medication adherence.

∗
Corresponding author: [email protected].

https://doi.org/10.1016/j.glohj.2021.11.006
2414-6447/Copyright © 2021 People’s Medical Publishing House Co. Ltd. Publishing service by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Pal P, Sambhakar S, Dave V, et al. Global Health Journal 5 (2021) 183–189

ease of use, dosage flexibility and cost. Examples of these technologies medications and bulk packaging to block counterfeiting of medications
include Med-ic® smart blister packaging and eCapTM pill bottles.15-16 in the supply chain.25-26 Medication prescribed to the patients is already
Smart blister packaging is considered as most preferable option for being embedded with RFID tags to enhance security and safety of drug
the employability of printed electronics. Presently available smart blis- use.27
ter packages continuously monitor the rupture of blisters by routing the RFID technology make use of radio-frequency waves to transmit and
conductive trace of circuits around the blister opening.17 On opening the receive data.28-29 RFID system consists of a tag i.e. transponder, tag
blister, the conductive trace around it is interrupted which is detected reader, database and software application. RFID tags comprises of a mi-
by an integrated circuit. The application of smart blister technology is crochip and antenna coil for establishing the communication. Transmis-
ideal for complex drug plans in which blisters possess different drugs sion of data occurs between distances from 10 m to 1 000 m. Stored
at different times. Ultimately, due to the circuit integrated in back foil data on RFID tags is transmitted along with the location of the linked
of blisters it is capable to detect whether the blister is opened or not. asset. Memory of the tag can be read-only or rewritable and specifi-
Several years ago, blisters incorporated with radio frequency identifi- cally contain storage capacity of 96 bits. A system to identify RFID tags
cation (RFID) technology were introduced. The smart blister pack of- based on their memory capacity and functionality is proposed by Auto-
fers advantages over other information technology healthcare systems ID Labs. Unlike barcode technology this technology does not demand
because its employability does not need the formation of a dedicated line-of-sight for data transmission. Additionally, data can be read au-
system or change design of traditional blister pack. In 2008, Jekle and tomatically via non-conducting material. RFID tags are tiny and can
Krämer demonstrated the reliability and functionality of smart blister be attached in different physical forms. Numerous computer hardware
packaging.18 technologies (smartphones, handheld readers, fixed point readers, desk-
The workflow of smart blister starts with the rupture of backfoil. top computers) can conveniently satisfy hardware and software require-
When a patient takes out the tablet, data regarding medication type, ments to store and read data obtained from RFID tags.
time of extraction and other allied information regarding dosage regi- Min et al. successfully demonstrated the RFID tracking of patients in
men is transmitted to a central data base through a smartphone appli- an outpatient clinic. They investigated that raw data obtained comprises
cation. This digital active monitoring technology helps the physicians of missed reads and contain noise due to which identification of the loca-
to cross-verify that patients have taken their dosage regimen at right tion of the tag was prevented.30 Sandberg et al. demonstrated that RFID
time or not. The applicability of this technology in health care builds system was used to track the patients who enters the wrong premises or
an interactive platform for communication between patients and physi- operating room and alert the medical professionals, which aided in the
cians. There are various merits of using this digital patient compliance reassigning of the patients within the matter of seconds.31 Marjamaa
monitoring tool such as reduced manual monitoring and documentation et al. improved the documentation process regarding timestamp by em-
work that will ultimately enhance the efficiency of a clinical trial, en- ploying the RFID automated process and compared the obtained results
hanced flexibility in deciding complex therapeutic treatments and trial with conventional process.32 Misidentification of patients in hospitals
workflows, decreased delinquency rate due to poor or inadequate com- can cause serious medical errors and is regarded as a potential risk to
pliance, enhanced data quality, shortening the duration of clinical trial patient safety.33 Positive patient identification application by utilizing
and accelerated approval process for new drugs and medicines.15 RFID technology includes a smart wristband fitted with a passive RFID
The concept of smart blister packaging has been discussed in various tag which is readable and used to identify the patient information such
patent applications. Peterson et al. demonstrated the concept of printed as name, date of birth, allergies, insurance information, medication re-
grid having resistive and conductive elements which will decide the ori- quirements and blood type.34-35 RFID technology when integrated with
entation of blister pack. For example, the rupture of the blister can be internet of things (IoT)-based sensors can help in collection of data and
detected by the alteration of the grid but in this concept, there is no patient monitoring. To monitor patients, Aguilar et al. suggested the ap-
way to find out which of the blisters is ruptured.19 Niemiec described plicability of implantable RFID that serves the function of collecting the
the ideology of multiplexed blister rupturing detection but it lacks any data regarding patient health, e.g., monitoring the body temperature of
type of embodiment.20 Brollier employed momentary switches aligned patients.36
in parallel to the micro-controller that facilitates to identify the time of RFID systems can also be employed in order to enhance drug com-
rupture but not the location.21 pliance of patients. Sun et al. demonstrated the working of wisely aware
RFID dosage (WARD) system by employing smart RFID wristbands on
2. Overview of RFID patients in combination with barcodes on drug packaging, can help in
minimizing the risk of medication error and develops the safe environ-
RFID was developed since the World War Ⅱ. Presently, this technol- ment in hospitals.37 Ajami et al. demonstrated the advanced version of
ogy is employed to integrate radio-identification on packaging into the the system that integrates the active and passive RFID tags that allows
labels and also to the blister packaging containing pills.22 Advancement pinpointing the location of patient in specific area and also helps in iden-
in RFID technology leads to its applicability in healthcare sector. In hos- tifying the correct dose of prescribed medication. Patient drug compli-
pitals, this technology is used in tagging individual pharmaceutical con- ance systems can also be used when patient leaves the hospital premises
tainers and monitoring the progress of medication. Also, various sensors by attaching the RFID tag to the packaging of the drug that will keep
embedded with RFID technology can be added to various items to mon- track of its opening and closing.34 However, more sophisticated systems
itor the human activity, e.g., monitoring patients regarding compliance. are now available in this aspect that includes smart blister packaging
Finally, a number of systems are available that provides monitoring ser- which records the information regarding rupturing of the blister. With
vices such as reminder systems, product handling and administration of the help of linked common database via a connected information sys-
medicines. RFID technology presently is being utilized in hospitals and tem, physicians and healthcare professionals can access this data in real-
healthcare centers for validating the identity of patients, active moni- time to monitor drug compliance of patients. Takacs et al. introduced
toring and tracking of patients and infants and to cross verify that right the patient compliance solution in which robot prototype is embedded
medication treatment is received by right patients or not.23 The RFID with face detection technology along with RFID tagged tablet dispenser,
embedded tracking system makes billing process more convenient and work in combination to monitor intake of medicines and improve drug
easier in hospitals by replacing the old and convectional pen and paper compliance.38 Similarly, a study demonstrated a prototype that attaches
system.24 RFID tags to medicines along with a RFID reader that functions in com-
Currently, Pharmaceutical companies are deploying RFID tags with bination with an online system that monitor the use of medications. This
their medications to ensure its safety and to track its inventory. Informa- system also alerts the healthcare professionals and personnel about the
tion technology company like IBM are deploying RFID tags on various expiration of the medications.39 Additionally, smart bandages equipped

184
Pal P, Sambhakar S, Dave V, et al. Global Health Journal 5 (2021) 183–189

with RFID technology are able to provide wound monitoring data of the 4. Smart blister and smart drawer
patients after their surgery that will ultimately help in controlled drug
delivery.33 In another study held at a Greek hospital, demonstration Smart blisters are referred as pharmaceutical packaging that pos-
of various applications of RFID technologies was carried out in which sesses the capability of tracking the action of taking out a pill. Besides
management of blood sample was made possible by utilizing blood bank this the printed circuitry in the packaging also collects the information
management system. The results of this study suggested that RFID along regarding the rupturing time, medication category and name, location
with barcode technology can help in better management of blood sam- etc. By utilizing the smart blisters patients can also get pill reminders on
ples and diminish the risk of misidentification of blood.40 their mobile phones. Additionally, if any type of misconception occurs
during the course of medication, both physician and patient can check
whether they have taken the prescribed medication at correct time or
not. This will minimize the medication error and create a two-way mon-
3. Adherence—a vital aspect itoring process that will ultimately help in enhancing the medication
adherence of patients.53
According to Delamater, “adherence” is the active, collaborative and A feasibility study reported the applicability of smart blister pack
voluntary involvement of the patient in a mutually acceptable course of technology for promoting medication adherence in 2012.54 Results
behavior to produce a therapeutic result.41 It means that patients and demonstrated the effectiveness of smart blister in recording patient re-
healthcare professionals should mutually agree on predefined goals re- lated data and other desired information. However, in 17% cases there
garding treatment and medical regimens. If these goals are not followed, were events of multiple tablet removal at same time, indicating the unin-
miscommunication between healthcare professionals and patients com- tentional breakage of tablets.54 Morak et al. developed a telemonitoring
promises the patient care and potential complications associated with solution to record patient medication intake which is based on smart
the disease may occur.3 , 42 Failure to adhere to the prescribed medi- blisters and applicability of mobile phones with near field communi-
cation is linked with higher relapsing rates, higher readmission rates, cation functionality. All the components work in conjugation to record
poor clinical outcomes, increased morbidity and mortality and increased drug-type, dosage information and timestamp. In this study 59 patients
healthcare costs.43-44 diagnosed with diabetes were monitored for the duration of 13 months.
According to WHO’s recommendation, adherence factors are catego- A total of 1 760 smart blisters were given to the patients and 14 843
rized into five dimensions, those associated with the healthcare team, events of taking out pill was recorded by the system. Results indicated
socioeconomics, therapy, patient and illness.45 Non-adherence to med- the feasibility of this monitoring solution to increase adherence of pa-
ication can also be regarded as either intentional or unintentional. In- tients.55
tentional non-adherence mentions those conditions in which patients Sometimes many patients fail to follow the exact procedure of med-
intentionally choose to either stop or reduce administering their pre- ication as prescribed by the healthcare professional. Specifically taking
scribed medications. It is completely depending on the motivation level the case of old age peoples who suffer memory loss, remembering the
of patients.46 Unintentional non-adherence is associated with patients’ procedure of the course of medication could be a challenging task. Fail-
lack of cognitive ability and capacity, that compromises the ability of ing in following the protocols of prescribed regimen can compromise the
the patients to adhere to the treatment regimen, e.g., cognitive impair- patient care and sometimes complications may occur. Aiming to keep
ment and forgetfulness can impact the patients’ adherence. The inten- this aspect in mind, Becker et al. created smart drawer project that pos-
tional and unintentional cases are not mutually exclusive concepts, as sess the capability to keep track of the inventory which is stored inside
poorly or less motivated patients, in most of the cases forget to take their the “drawer” and recording, monitoring the patient’s drug taking activ-
medicines.46 For developing the better understand of the adherence as- ity.56 The underlying fundamental concept behind the smart drawer is
pects all potential factors must be screened and selected.45-47 its capability to scan for identification and to recognize the opening and
Blair et al. analyzed data obtained from randomized controlled trial shutting of the “drawer” along with recording those activities with a
of foster-parent child dyads who received parent child interaction ther- timestamp. By integrating proper software and hardware, a system was
apy, which exhibited that rates of non-adherence, treatment attrition created to monitor the drug taking activities of the patient and alert him
and non-response were significantly decreased.48 Another study iden- in the cases of not following the protocols of prescribed treatment. In
tified the factors influencing adherence and monitored the adherence this case, this system has three main users—the caregiver, the patient
of patients who receiving the treatment of diabetes mellitus, dyslipi- and the maintainer. Each of them has access to different user interface of
demia and hypertension. In this study, 16 208 patients aged ≤ 65 years the system. User interface of the caregiver offers functions like retrieving
were involved and monitored their adherences by calculating the medi- medication history of the patient and options to modify and enter the
cation possession ratio. Results indicated that 3%‒8% increment in ad- new prescriptions to the system. In case of patient, it includes function-
herence was observed for each diseased case and mental condition did alities like alert system for cases when patient intentionally or uninten-
not affect the patients’ adherence.49 Similarly, Rubens et al. explored tionally forgets to take the prescribed medication, options to retrieve his
the link between treatment adherence and HIV associated stigma. The medication history, instruction regarding the correct use of the drugs.
coping strategies along with treatment adherence measured through The maintainer will act as the administrator of the system and provided
questionnaires. Results indicated that the quality of care and perceived with the choice of adding and removing the functionalities of this sys-
stigma points significantly predicted the adherence to the prescribed tem and accessing the stored data. This type of programmable system
treatment.50 can be utilized as an autonomous tool or could be added to a larger
In 2019, a study developed a web-based aftercare program for environment where patterns regarding medications are correlated with
women suffering with severe and chronic bulimia nervosa and exam- other patients.56
ined the adherence to this program. A decline in adherence during the
course of intervention was observed, although adherence was not asso- 5. Adherence monitoring systems
ciated with severity and overall illness and it did not affect the outcomes
of intervention.51 In China, Chen et al. conducted a qualitative study in 5.1. iCabiNET
which text message-based intervention program was tested for increas-
ing the adherence of patients’ in rural area. The findings showed that In 2008, Lopez-Nores et al. introduced a system referred as iCabi-
the rural patients were not much aware about the disease from which NET. This system consists of sensors, RFID tags and smart packaging
they are suffering, though a large portion of the patients had positive systems that work collectively to track the drug names along with avail-
attitude towards text message-based intervention program.52 able doses with high degree of precision and negligible risk of selecting

185
Pal P, Sambhakar S, Dave V, et al. Global Health Journal 5 (2021) 183–189

one drug for another, and makes use of residential environment and of study, the GlowCapTM precisely recorded the data regarding adher-
interact with appliances installed in house and communicate with the ence. Results identified that there were two barriers in adherence, i.e.,
outside world via a residential gateway. The iCabiNET collects the data lack of reminders and absence of medicine home delivery service.58
regarding available drugs and doses by employing RFID readers that
are installed in premises of user’s house or residential area. A module 5.4. Medication event monitoring system (MEMS®)
referred as “watchdog” processes the information to verify that drugs
are in good condition or not and doses correctly deplete with the course MEMS® is a customizable medication package manufactured by a
of time, as per the protocols and guidelines defined by health organiza- Swiss company. It is capable of recording and storing upto 4 000 dos-
tions, retailers and drug manufacturers. The watchdog collects the data ing events. This system is integrated with microcircuits that possess the
regarding gender, age and warns about any type of odd circumstances capability to record the date and time whenever the package is opened.
by generating different predefined events. Another module known as This system offers two options namely, SmartCap and TrackCap. Smart-
“Actuator” considers the triggered events as input, and identifies the ac- Cap offers the option of liquid crystal display screen which shows the
tions to carry out for the user. Finally, the actuator identifies the generic time elapsed since last dose and number of doses taken by patient in the
actions by employing appliances that are driven by the network registry last 24 h. Both options are available in wide range of shape and size.59
of connected appliances linked to the residential network for the final In a study conducted by Diaz et al., the feasibility of MEMS® sys-
operation. For example, if the user is watching TV or sleeping or he may tem was tested to promote the medication compliance in patients diag-
be out of home, the generic action is to “warn the user” with the help nosed with schizophrenia. A total of 35 patients were involved in this
of triggering an alarm, disturb the TV program and show some message study out of which 14 were admitted to a psychiatric hospital. After
on screen or make a telephonic call.57 the treatment of subjects with anti-psychotic medication in the hospital
they were discharged from hospital after giving their prescribed med-
5.2. WARD system ications in MEMS® packaging. The initial 6 patients were advised to
return to hospital on monthly basis for data retrieving and remaining
The WARD system ensures patient safety by retrieving data from 8 were advised to return weekly during first month and after that ev-
RFID tags. Data regarding patient is retrieved by employing RFID tags ery two weeks. The data was collected for the duration of 6 months.
and is integrated with the central database of medication to ensure that Results obtained in this study demonstrated that mean compliance rate
medication that may cause allergy or other harmful effect to the patient during the first month was 63% and decreases up to 45% in subsequent
is not dispensed in any case. The main aim of developing this system is months.60-61
to eliminate any ambiguity regarding the drug prescribed to the patient In another study, Gillespie et al. described the applicability of
so that medical practitioners can track the medicines that are prescribed MEMS® system for the comprehensive assessment regarding adherence
to the patient by using RFID technology. The WARD system involves the of prescribed medication in subjects diagnosed with chronic aspects of
employability of barcode on each unit dose medicine that act as index ulcerative colitis. Subjects were administered with medications in pack-
of patient’s medical order and every patient is required to wear a wrist- age integrated with MEMS® technology and asked various questions
band integrated with RFID tag. Various events that occur during the related to the adherence. Results indicated that promoting adherence
course of whole medication procedure is handled and managed by per- using intelligent systems like MEMS® facilitates the systematic depic-
sonal computer (PC) integrated on the cart handle and personal digital tion of the complexities in patient adherence that may not be possible
assistant (PDA) that carry out the data handling procedures. Addition- through by any other means.62
ally, the pharmacy staff of the hospital can monitor the dispatch and Rollings et al. conducted a study to carry out comparative study of
packaging procedures to minimize the medication errors by employing the MEMS® system and manual monitoring of the adherence aspects
the PC. The hospital information system notifies the pharmacy staff to of twice-day oral dosing schedule in patients diagnosed with mild asth-
carry out the drug packaging procedures, once the physician issued an matic condition. Adherence of patients was promoted by integrating the
order. The WARD system on integration with hospital information sys- MEMS® system with inhalers that were administered in double-blind
tem comprises of three parts, namely pharmacy, bedside and associated manner. The results of this study exhibited that excellent agreement be-
parts. The pharmacy sub-part will carry out the printing the barcodes tween both the methods of promoting adherence favors the applicability
on medications. Printed barcodes are considered as identities of specific and feasibility of MEMS® technology for patient tracking and monitor-
medicine that holds the detailed information regarding various medi- ing.63
cations which is stored in a central database. The bedside subpart will
cross verify the prescribed medication with the patients so that there 6. mHealth —an emerging aspect
would not be the chances of medication error. Finally, the conforming
sub-part identifies the patients. In this way the medication errors can be According to WHO, mHealth or mobile health is regarded as prac-
minimized in hospitals to a greater extent.34 , 37 tices concerning public and medical health that are aided by the mo-
bile device such as PDAs, mobile phones, patient monitoring devices
5.3. GlowCapTM and other wireless devices. mHealth utilizes the mobile phone utility
of voice and short messaging service (SMS) along with complex appli-
The GlowCap𝐓𝐌 employs a wireless connection to notify the patients cation and services like infrared, bluetooth, global positioning system,
to take their medicine and plays an alarm tone to remind the subject third and fourth generation mobile telecommunications (3 G and 4 G
about their dose schedules. This reminder system is developed to elimi- technology).64 In 2009, WHO conducted a survey considering mHealth
nate business and health problems by using a smart cap connected with in various regions. Results obtained in survey demonstrated that more
internet. In a study conducted by Inoue et al., GlowCapTM was employed than 80% of the participating member states confirm the existence of at
to monitor the adherence of hydroxyurea medication prescribed to chil- least one mHealth initiative in country. Among the participating groups,
dren diagnosed with sickle cell disease, which aiming to determine the 75% reported the presence of four or more types of mHealth initia-
applicability of this device in enhancing the adherence of subjects. A tives. There were only 19 countries that did not confirm the existence of
total of 19 subjects were incorporated in this study and they were pro- mHealth initiative. However, zero reporting of mHealth initiatives does
vided with 37-item questionnaire and were asked to use GlowCapTM not mean that no mHealth initiatives are being carried out in countries.
containing hydroxyurea. Out of 19 subjects involved 17 were in the in- Local and small mHealth project being carried out by non-government
tervention phase. Among the 17 subjects, 12 subjects exhibited reliable or private organizations that may not be extensively recognized. Addi-
adherence data with a median adherence rate of 85%. During the course tionally, the survey was restricted by the fact that participants could

186
Pal P, Sambhakar S, Dave V, et al. Global Health Journal 5 (2021) 183–189

only provide the instance of each mHealth group. Therefore, the fre- tracks the patient dosage activity.65 The dosage activity of the patients
quency of the mHealth initiatives reported demonstrated the scope of can be viewed online by physicians or patient or caregivers and is pro-
mHealth projects in a country but does not depict the detail of project grammed remotely through wireless connection. It gives the features of
within each category.64 complete reminders by employing beeps, text-messages, e-mail, beeps
Participating African regions reported very less projects regarding and flashing lights. Also, the system can be programmed to send weekly
mHealth, while in southeast Asian regions reporting was more. Accord- reports via email. The development of medicine prescribing computer
ing to the World Bank, the low-income participant groups reported very programs that are connected to an online pharmacopeia aids in identify-
few mHealth initiatives in their regions. However, the results of high- ing side-effects, indications, contra-indications as well as drug interac-
income category were not significantly higher when compared to low tions will ultimately enhance the accuracy and legibility of prescribed
income groups regarding the context of mHealth. Depending on the di- medications. These improvements can be utilized for providing more
verse localization of reported mHealth projects initiatives both econom- safe and efficient prescribing practices that can help the patients for
ically and geographically, it seems that mHealth is a methodology that which the treatment is prescribed.
possess global appeal.64 The participating countries that reported the The growing applications of mobile phones or similar devices that
mHealth initiatives includes emergencies, emergency toll free services, can be carried close proximity with its owners, integrated with SMS
mobile telemedicine, healthcare telephone helplines and healthcare call utility and automated message sending, has increased the frequency of
centres. These mHealth project initiatives functions on the voice func- employing voice calls and SMS for health allied calls. Mobile phones
tionality of mobile phone and depicts the major portion of these projects. and devices are specifically employed for appointment reminders that
There were also the projects that involve the applicability of mobile ultimately enhance the adherence. Apps for smart phones can also pro-
phone in surveillance, decision support systems, health surveys and vide services like heart rate monitor, body temperature monitor, elec-
awareness raising campaigns. The results that were obtained from the trocardiogram etc. that can be more useful in monitoring the health and
present literature were different from the reports that advocate the ap- prevents any type of misconception regarding health.
plicability of mobile phone in disease surveillance and data collection. Interaction of patients with the physicians establishes the platform
However, most of the studies were based on perceiving the effectiveness, for whether patients have confidence in the prescribed medication or
feasibility and differences between convectional approaches of data col- not. The vitality of confidence and trust for the physician is very critical
lection and surveillance of diseases to mHealth solutions. Therefore, inpatient adherence. Advanced technology may have positive or nega-
these project initiatives may not be visible to government informants tive effect on aspects associated with patient adherence, based on the
or officials that conduct the survey.64 attitude and behavior of the medical practitioners. The accessibility of
Subsequently, it is important to note that diagnosing a disease with online information regarding prescribed medications (due to miscom-
the help of mobile phone requires that integration of more sophisticated munication between physician and patient which leads to its verifica-
technology. Since this would require integration of more specific sensors tion) can result in lack of desire in administering new medications if
that could detect the presence of disease by simply opening a program the risks behind them are not given. This results in consumption of time
that receives and transmits diseases related data from the central servers during the course of medication. However, the time spent in attend-
and by incorporating the application of artificial intelligence the dis- ing the concerns of patients can build the better relationship between
eases can be identified. Such initiatives are expected to increase in near patient and physician, sometimes results in alteration in diagnosis and
future, however, as artificial intelligence is becoming more advanced therefore indirectly enhances the adherence. New technologies can aid
day by day. health care providers in providing information via distance education
for professional development.
7. Impact of smart technologies on healthcare systems
8. Challenges to smart technologies concerned with improving
Advanced technology has collaborated in numerous ways to reveal adherence
the probability of pharmacological treatment ultimately. Understanding
the various pathways and development of better treatments does not Till date, European Medicine Agency and U. S. Food and Drug Ad-
benefit instantly until they are subjected to validate the benefits pos- ministration do not implement smart adherence monitoring systems in
sible. However, numerous studies have demonstrated that adherence case of clinical trials. Also, International Council on Harmonization of
holds the good impact on economic and clinical outcomes as well as on Technical Requirements for Registration of Pharmaceuticals for Human
utilization of health services. Use (ICH) has changed its ICH-E9 guideline introducing the new term
Cost is important factor in deciding whether patients repurchase the “estimand” which is related to technical requirements for Pharmaceuti-
prescribed medications or not. Therefore, factors that aid in lowering cals for human use.66 Previously, the efficacy of the analysis of the drug
the cost of medications will surely help in improving the adherence. For was purely based on principle of intention-to treat but the revised guide-
some medicines, modern technology has aided in lowering the price of line speculates a more accurate parameter of treatment effect which de-
the drug and also improved its safety. The efforts to promote generic fines the dealing parameters in case of non-adhering patients. However,
prescribing are important measure in reducing cost. The utilization of there was no citation of difference between poor adherers, non-initiators
internet now offers various generic alternatives of costly drugs. Now and discontinued patients. This ultimately hinders appropriate distinc-
patients can obtain more information about their diseases by utilizing tion between a simply non adhering and true ‘pharmacological’ non re-
the web-services supported by the internet to understand and manage sponder patient.67 In the screening of efficacy of drug, it is very im-
their diseased condition which comprises of decreasing the costs of their portant to think on this distinction before concluding that drug is not
prescribed medication, such as anti-cancer medications. Many patients therapeutic based on black box of real time medication use. Therefore,
having chronic diseases are provided with different medication regi- the need of formal guidelines is required; this would require joint efforts
mens that are to be taken with varying schedules, that includes grow- of healthcare professionals and regulators.
ing number of geriatric patients diagnosed with memory and cognitive Indian government has set up primary healthcare centers (PHC)
problems, various pharmacies have started packing the medications in throughout the country to provide affordable and quality healthcare
dosette box or Webster-pak® which employs advanced technology to services. However, the connectivity at these PHCs is not satisfactory.
seal the medicines into blister packs that blocks the mixing up of vari- Therefore, PHCs are unable to offer real-time healthcare solutions to
ous medications, clearing the confusion of taking the medications. Tech- the patients based in remote areas. The mHealth infrastructure in India
nology provided more potential of advanced pill box systems, in which must undergo strict and drastic alterations. There is a need to make cost
product is linked through wireless connection to a central server that effective and sustainable ecosystem and infrastructure that will facili-

187
Pal P, Sambhakar S, Dave V, et al. Global Health Journal 5 (2021) 183–189

tate implementation of mHealth across the country. The capital required 16. Mediary Corp. eCapTM . https://www.informationmediary.com/nfc-smart-packaging-
to develop this infrastructure is a big concern as there are inadequate devices/ecap-smart-pill-bottle/. Accessed July 10, 2021.
17. Petersen M., Wilson A. Blister package with electronic content monitoring system.
funds available. Solution for facilitating enough funds for development http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO03055769. Accessed July
of stable healthcare infrastructure is to pool funds and resources from 10, 2021.
other schemes of government that will ultimately create a robust infras- 18. Jekle C, Krämer I. OtCM (Objective therapy Compliance Measurement): smart blister
packages for measuring patient compliance. Hosp Pharm Eur. 2008;40:47-50.
tructure that will ultimately serve various sectors such as healthcare, 19. Petersen M., Wilson A., Sherstyuk M. Method for manufacturing a conductive grid
education, finance etc. for attachment to a blister package. http://www.patentbuddy.com/Patent/7937829.
Accessed July 10, 2021.
20. Niemiec M.A. Drug delivery management systems. https://uspto.report/patent/
9. Conclusion grant/6,574,166. Accessed July 10, 2021.
21. Brollier B.W. Momentary switch integrated in packaging of an article. http://v3.
There exist many ways in which the capacity and inventiveness of espacenet.com/textdoc?DB=EPODOC&IDX=WO2007070487. Accessed July 10,
2021.
humans in problem solving and inventing new devices have collabo- 22. Connolly C. Sensor trends in processing and packaging of foods and pharmaceuticals.
rated in advancement of medical sector which helps in improving life Sensor Rev. 2007;27(2):103-108.
expectancy of human in modern world. Although various medications 23. Rosenbaum BP. Radio Frequency Identification (RFID) in Health Care: privacy and
security concerns limiting adoption. J Med Syst. 2014;38(3):19.
aids in controlling diseases and enhancing as well as becoming more
24. Cangialosi A, Monaly JE, Yang SC. Leveraging RFID in hospitals: patient life cycle and
sophisticated in their advancement. Despite the advances, adherence mobility perspectives. IEEE Commun Magaz. 2007;45(9):18-23.
remains a major concern. Modern medicines, formulations and method- 25. Datz T. Drugmakers Testing RFID Tags: counterfeit drugs are as common as a knock-
off Hermès tie or Prada bag on the streets of Manhattan. https://www.csoonline.
ologies to improve adherence are being developed and trialed consis-
com/article/2118948/drugmakers-testing-rfid-tags.html. Accessed July 10, 2021.
tently. Utilization of numerous methodologies that aids in adherence is 26. Brewin B. FDA Backs RFID Tags for Tracking Prescription Drugs: calls for drug makers
proven to be most effective. Despite all the advanced technology, mo- to use them on shipping pallets and cases by 2007. https://www.computerworld.com/
tivation, self-efficacy and patient beliefs the relationship of doctor and article/2575045/fda-backs-rfid-tags-for-tracking-prescription-drugs.html. Accessed
July 10, 2021.
patient remains very important which reflects that medicine practice is 27. Swedberg C. Hospital pharmacies using RFID-enabled medication from QuVa Pharma.
an art not just a science. https://www.rfidjournal.com/articles/view?17148. Accessed July 10, 2021.
28. Ashar BS, Ferriter A. Radiofrequency identification technology in health carebenefits
and potential risks. JAMA. 2007;298(19):2305-2307.
Acknowledgements 29. Yao W, Chu CH, Li Z. The adoption and implementation of RFID technologies in
healthcare: a literature review. J Med Syst. 2012;36(6):3507-3525.
Authors are highly obliged to Banasthali Vidyapith, Rajasthan boost- 30. Min D, Yih Y. Fuzzy logic-based approach to detecting a passive RFID tag in an out-
patient clinic. J Med Syst. 2011;35(3):423-432.
ing authors for upgrade their knowledge of the present work. 31. Sandberg WS, Häkkinen M, Egan M, et al. Autoion and notification of "wrong pa-
tient-wrong location’’ errors in the operating room. Surg Innov. 2005;12(3):253-
Competing interests 260.
32. Marjamaa RA, Torkki PM, Torkki MI, Kirvelä OI. Time accuracy of a radio fre-
quency identification patient tracking system for recording operating room times-
The authors declare that they have no known competing financial tamps. Anesth Analg. 2006;102(4):1183-1186.
interests or personal relationships that could have appeared to influence 33. Podaima BW, Friesen M, McLeod RD. A review of emerging smart RFID in healthcare.
CMBES Proc. 2010;33(1).
the work reported in this paper. 34. Ajami S, Rajabzadeh A. Radio Frequency Identification (RFID) technology and patient
safety. J Res Med Sci. 2013;18(9):809-813.
References 35. Tzeng SF, Chen WH, Pai FY. Evaluating the business value of RFID: evidence from
five case studies. Int J Product Econ. 2008;112(2):601-613.
1. Velligan DI, Kamil SH. Enhancing patient adherence: introducing smart pill devices. 36. Aguilar A.W., van der Putten W., Maguire G.Q. Positive patient identification
Ther Deliv. 2014;5(6):611-613. using RFID and wireless networks. http://citeseerx.ist.psu.edu/viewdoc/citations;
2. Chaudri NA. Adherence to Long-term Therapies Evidence for Action. Ann Saudi Med. jsessionid=F1ACCE49AD588F32D34CCA0C0D76E41B?doi=10.1.1.115.709. Access
2004;24(3):221-222. ed July 10, 2021.
3. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 37. Sun PR, Wang BH, Wu F. A new method to guard inpatient medication safety by the
2011;86(4):304-314. implementation of RFID. J Med Syst. 2008;32(4):327-332.
4. Hall AE, Paul C, Bryant J, et al. To adhere or not to adhere: rates and reasons 38. Takacs B, Hanak D. A prototype home robot with an ambient facial interface to im-
of medication adherence in hematological cancer patients. Crit Rev Oncol Hematol. prove drug compliance. J Telemed Telecare. 2008;14(7):393-395.
2016;97:247-262. 39. Kurnianingsih M.A.H., Prabuwono A.S. HoMeTrack: rFID-based localization for
5. Alomi YA, Al-Shubbar N, Lubad N, Albusalih FA. Adherance assessment of medication hospital medicine tracking system. https://www.kau.edu.sa/Files/830/Researches/
errors Repoting system at the public hospital in Riyadh, Saudi Arabia. Int J Pharm Clin 66808_38353.pdf. Accessed July 10, 2021.
Sci. 2019;8(2):105-109. 40. Katsiri E, Pramatari K, Billiris A, Kaiafas A, Christodoulakis A, Karanikas H. RFCure:
6. Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med. an RFID based blood bank/healthcare information management system. In: Kyria-
2005;353(5):487-497. cou E, Christofides S, Pattichis C, eds. XIV Mediterranean Conference on Medical and
7. Nilsson HE, Unander T, Siden J, et al. System integration of electronic func- Biological Engineering and Computing 2016. IFMBE Proceedings, vol 57. Cham: Springer;
tions in smart packaging applications. IEEE Trans Compon Packag Manufact Techn. 2016.
2012;2(10):1723-1734. 41. Delamater AM. Improving patient adherence. Clin Diabetes. 2006;24(2):71-
8. Volpp KG, Loewenstein G, Troxel AB, et al. A test of financial incentives to improve 77.
warfarin adherence. BMC Health Serv Res. 2008;8(1):272. 42. Swieczkowski D, Mogielnicki M, Cwalina N, et al. Medication adherence in patients
9. Velligan D, Mintz J, Maples N, et al. A randomized trial comparing in person and after percutaneous coronary intervention due to acute myocardial infarction: from
electronic interventions for improving adherence to oral medications in schizophre- research to clinical implications. Cardiol J. 2016;23(5):483-490.
nia. Schizophrenia Bull. 2012;39(5):999-1007. 43. Allonen J, Nieminen MS, Lokki M, et al. Mortality rate increases steeply with non-
10. Liu MWC, Chien LY, Syukri M. Mon-064 barriers and facilitators of adhering to the adherence to statin therapy in patients with acute coronary syndrome. Clin Cardiol.
treatment regimens among patients receiving hemodialysis in Banda Aceh, Indonesia: 2012;35(11):E22-E27.
a Qualitative Ecological Evaluation. Kidney Int Rep. 2019;4(7):S330. 44. Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a
11. Park LG, Howie-Esquivel J, Dracup K. Electronic measurement of medication adher- broad range of adverse outcomes in patients with coronary artery disease. Am Heart
ence. West J Nurs Res. 2014;37(1):28-49. J. 2008;155(4):772-779.
12. Checchi KD, Huzbrechts KF, Avorn J, Kesselheim AS. Electronic medication 45. Chaudri NA. Adherence to long-term therapies: evidence for action. Ann Saudi Med.
packaging devices and medication adherence: a systematic review. JAMA. 2004;24(3):221-222.
2014;312(12):1237-1247. 46. Molloy GJ, Messerli-Bürgy N, Hutton G, Wikman A, Perkins-Porras L, Steptoe A. Inten-
13. Bisharat B, Hafi L, Baron-Epel O, Armaly Z, Bowirrat A. Pharmacist counseling to tional and unintentional non-adherence to medications following an acute coronary
cardiac patients in Israel prior to discharge from hospital contribute to increasing syndrome: a longitudinal study. J Psychosom Res. 2014;76(5):430-432.
patient’s medication adherence closing gaps and improving outcomes. J Transl Med. 47. Rushworth GF, Cunningham S, Mort A, Rudd I, Leslie SJ. Patient specific factors re-
2012;10(1):34. lating to medication adherence in a post percutaneous coronary intervention cohort.
14. Thompson SC, Walker AT. Use of modern technology as an aid to medication adher- Int J Pharm Pract. 2012;20(4):226-237.
ence: an overview. Patient Intell. 2011;3:49-55. 48. Blair K, Topitzes J, Mersky JP. Brief, group-based parent-child interaction therapy: ex-
15. Mediary Corp. Med-ic®. https://www.informationmediary.com/nfc-smart-packaging- amination of treatment attrition, non-adherence, and non-response. Child Youth Serv
devices/med-ic-electronic-medication-blister/. Accessed July 10, 2021. Rev. 2019;106:104463.

188
Pal P, Sambhakar S, Dave V, et al. Global Health Journal 5 (2021) 183–189

49. Juste MA, Miguel AG, Plou BP, et al. Adherence to treatment of hypertension, hyper- 58. Inoue S, Kodjebacheva G, Scherrer T, et al. Adherence to hydroxyurea medication by
cholesterolaemia and diabetes in an elderly population of a Spanish cohort. Med Clín children with sickle cell disease (SCD) using an electronic device: a feasibility study.
(Barc). 2019;153(1):1-5. Int J Hematol. 2016;104(2):200-207.
50. Rubens M, Saxena A, Ramamoorthy V, et al. HIV-related stigma, quality of care, and 59. WestRock. MEMS® Cap Medication Event Monitoring System. https://www.
coping skills: exploring factors affecting treatment adherence among PLWH in Haiti. westrock.com/en/products/folding-cartons/memscap. Accessed July 10, 2021.
J Assoc Nurses AIDS Care. 2018;29(4):570-579. 60. Diaz E, Levine HB, Sullivan MC, et al. Use of the Medication Event Monitoring System
51. Beintner I, Jacobi C. Internet-based aftercare for women with bulimia nervosa follow- to estimate medication compliance in patients with schizophrenia. J Psych Neurosci.
ing inpatient treatment: the role of adherence. Internet Interv. 2019;15:67-75. 2001;26(4):325-329.
52. Chen XZ, Yu SJ, Li CY, Zhan XX, Yan WR. Text message–based intervention to improve 61. Haberer J. Medication event monitoring systems, In: Gellman MD, ed. Encyclopedia
treatment adherence among rural patients with type 2 diabetes mellitus: a qualitative of Behavioral Medicine. Cham: Springer; 2020.
study. Public Health. 2018;163:46-53. 62. Gillespie D, Hood K, Williams A, Stenson R, Probert C, Hawthorne A. The use of the
53. Healthcare PACKAGING. Schreiner MediPharm: smart Blister Pack for Clinical Trials: Medication Event Monitoring System (MEMS) for assessing medication adherence for
digital tools help manage and track process, turning an ordinary blister pack into an chronic conditions: use and results from a 12 month trial of patients in remission with
efficient patient compliance montoritoring tool. https://www.healthcarepackaging. ulcerative colitis (UC). Trials. 2011;12(Suppl 1):A130.
com/issues/regulatory/press-release/13294889/ 63. Rollings NJ, Zimmerman RR, King TS, Sorkness CA. Medication event monitoring
schreiner-medipharm-smart-blister-pack-for-clinical-trials. Accessed July 10, 2021. system (MEMS®): the asthma clinical research network (ACRN) experience. J Allergy
54. van Onzenoort HA, Neef C, Verberk WW, van Iperen HP, de Leeuw PW, van der Clin Immunol. 2004;113(2 Suppl):S158.
Kuy PHM. Determining the feasibility of objective adherence measurement with blis- 64. World Health Organization. mHealth: New Horizons for Health Through Mobile Tech-
ter packaging smart technology. Am J Health-Syst Pharm. 2012;69(10):872-879. nologies. Geneva: World Health Organization; 2011.
55. Morak J, Schwarz M, Hayn D, Schreier G. Feasibility of mHealth and Near Field Com- 65. MedMinder. MedMinder is more than just a pill dispensers. https://www.medminder.
munication technology based medication adherence monitoring. Annu Int Conf IEEE com/pill-dispensers-2/. Accessed July 10, 2021.
Eng Med Biol Soc. 2012;2012:272-275. 66. European Medicines Agency. ICH E9 (R1) addendum on estimands and sensitivity
56. Becker E, Metsis V, Arora R, Vinjumur J, Xu YR, Makedon F. SmartDrawer: RFID-based analysis in clinical trials to the guideline on statistical principles for clinical trials.
smart medicine drawer for assistive environments. Proceed Int Conf PErvasive Technol https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e9-r1-addendum-
Relat Assist Environ. 2009;49:1-8. estimands-sensitivity-analysis-clinical-trials-guideline-statistical-principles_en.pdf.
57. Lopez-Nores M, Pazos-Arias JJ, Garcia-Duque J, Blanco-Ferndndez Y, Romos– Accessed October 6, 2021.
Cabrer M. Introducing smart packaging in residential networks to prevent medicine 67. Vrijens B, De Geest S, Hughes DA, et al. A new taxonomy for describing and defining
misuse. IEEE Int Sympos Consum Electron. 2008:1-3. adherence to medications. Br J Clin Pharmacol. 2012;73(5):691-705.

Edited by Jie Yan

189