Summary of medication adherence monitoring strategies and technologies currently being pilot-tested or implemented in clinical settings for tuberculosis care
| Description of monitoring approach or technology | Estimated range of costs in US dollars (select examples of technologies) | Sites of implementation | Reminder function | Approach to digital observation | Healthcare provider (HCP) interface | Triage function | |
| Self-administered therapy (SAT) | Patients take medications themselves without any formal dose observation strategy.10 Clinic visits may be combined with additional adherence monitoring approaches, such as urine isoniazid testing71; however, this has not been done routinely in national TB programmes. | Variable based on the setting. This represents the base cost of care provision, with most adherence monitoring strategies outlined below adding costs on top of this value. | Standard of care in countries not implementing DOT. De facto standard of care in settings where DOT is not functioning optimally.27 29–31 | Reminders about adherence may take place during routine clinic visits. | Adherence evaluation may take place during clinic visits via basic questions asked by HCPs to patients or less commonly by pill counts.59 | Face-to-face interactions during follow-up visits. | Patients are generally provided with uniform (undifferentiated) care, though referrals to counsellors and other services are possible. |
| Directly observed therapy (DOT) | Facility-based DOT: patient visits health facility to be observed taking every medication dose (most common DOT model in LMICs).10
Home-based DOT: HCP visits a patient’s home to observe her take each dose.10 Community-based or family-based DOT: family member or community resident observes patient taking each dose.10 | Variable based on the setting and DOT model, with facility-based models generally having lower costs than in-person DOT using home visits, due to lower personnel and travel costs. | Standard of care for monitoring TB medication adherence in many countries.22 89 | Reminders are not routine; however, the health system is supposed to take prompt action if patients do not show up to facilities for DOT. | HCP or other designated individual observes a patient swallow the dose. | Frequent face-to-face interactions with HCPs or other designated individual. | Patients are generally provided with uniform care, regardless of the risk of non-adherence. |
| Short message service (SMS)–based strategies | SMS texting can remind patients to take TB medication doses (one-way SMS).39 68 79 Patients may respond by SMS text or phone call to indicate a dose taken (two-way SMS). Often used in combination with other DATs.39 90 | In nearly all settings, costs are generally low (eg, less than US$1 to US$2 per patient per treatment course), assuming that patients can access a feature phone. | Interventions in numerous African countries,78 79 91–94 China,39 95 Indonesia,96 Thailand,97 India90 and Pakistan68 have used one-way SMS reminders, or two-way SMS alone or in combination with other adherence monitoring strategies.98 | Prescheduled, automated SMS text reminders can be sent to a patient’s mobile phone each day and repeated multiple times (or reminders sent to HCPs or family members) if patients do not respond to report a dose taken.68 78 79 | Patients respond to the reminder SMS via response SMS text or free call.68 78 79 | HCPs access dosing histories compiled from patients’ SMS or phone call responses through online portals accessible on computers or smartphones.79 90 | Patients who do not respond to reminder SMS texts can be triaged to receive additional reminder texts or personalised SMS texts or phone calls from HCPs encouraging them to continue therapy or return to the clinic for evaluation.68 79 |
| 99DOTS | TB medications are issued in blister packs wrapped in an envelope. On dispensing a dose, a hidden phone number is revealed on the inner envelope flap, prompting the patient to place a toll-free call to indicate a dose taken.34 87 | Estimated cost per patient per treatment course in LMIC settings is US$5 to US$6, with roughly half of costs related to the custom envelopes and half related to technology, including communication costs for SMS texts and missed calls. This assumes patients can access a feature phone for calling the toll-free numbers.34 | Over 150,000 patients with TB have been registered in India, along with a smaller number in Myanmar.34 | Patients receive automated SMS reminders every day, with additional reminders if doses are missed. | Phone numbers that are unpredictable to the patient are revealed with each dispensed dose. Calling the phone number therefore indicates that a specific dose was taken.34 87 | HCPs can receive SMS text notifications regarding potentially non-adherent patients and monitor patients’ adherence in real time through an online portal accessible on computers or smartphones.34 87 | Patients are triaged into risk groups based on the frequency of unreported doses. HCPs can follow up with phone calls or home visits.34 |
| Video DOT (VDOT) | Synchronous VDOT: prescheduled live-streaming video conferencing through a secure interface allows an HCP to watch a patient take her TB medications at home in real time.67
Asynchronous VDOT: patient sends a pre-recorded video of herself taking medications using a smartphone or webcam to HCP, who views the video and confirms adherence.53 64 ‘Observation’ can also be automated by use of facial recognition and medication identification software, saving time for HCPs.35 | For a 6-month course of daily treatment, subscription costs for the SureAdhere application are approximately US$210 (US$35 per month) in developed countries and US$24 (US$4 per month) in LMICs. For patients who do not already have a smartphone or tablet with data services, the estimated additional cost for a TB programme in the USA to equip their patients is approximately US$324 (US$54 per month) for data services and US$100 for a smartphone. Data services may be less expensive in LMICs than in high-income countries. | Mostly middle-income and high-income countries (eg, Mexico, USA,99 England, Singapore) where smartphones are reliable and widely available,35 53 64 67 100 though pilot studies have been conducted in Kenya54 and Vietnam.101 | SMS texts can be sent to remind patients of their next videoconferencing appointment or to record and submit a video.53 67 | Patient names and swallows each pill in front of the camera.67 HCP observes the dose live or asynchronously,53 67 or ‘observation’ can be automated using facial recognition and medication identification software.35 | Live-streaming VDOT interface has benefits other than observation since HCPs can ask patients about medication adverse effects.67 Computer portal also shows patient’s dosing history. | Uniform (undifferentiated) care is provided to patients. Missed VDOT appointments or pre-recorded videos are followed up by phone calls or home visits.53 67 |
| Digital pillboxes | Digital pillboxes store TB medications and have pre-programmed audiovisual reminders embedded in the pillbox. Opening and closing the box to access medications serves as a proxy indicator of a dose taken. This information is transmitted via a SIM card to create a real-time dosing history accessible by HCPs.39 57 102 | Device costs range from as low as US$14 for evriMED cardboard frame devices that do not provide data in real time to US$23 for evriMED plastic frame devices that deliver information in real time, to US$130 for Wisepill devices that provide information in real time. | Used in research studies for patients with drug-susceptible (DS) TB in China,39 57 Tanzania103 and Uganda and for patients with DS and MDR TB in India.88 | Present as digital displays, alarms or automated voice alerts integrated within the pillbox. Patient stops receiving reminders for the day after the box has been opened.39 | Opening the digital pillbox serves as a proxy indicator for a dose taken, though it does not ensure actual ingestion. Failure to open the pillbox on a given day serves as a proxy indicator for a missed dose. | HCPs can view dosing histories through an online portal or get alerts about missed patient doses via SMS.39 102 | In a study in China, patients who missed 3 to 6 doses based on a digital pillbox–compiled history were triaged to a weekly HCP visit and patients who missed seven or more doses were triaged to in-person DOT.39 |
| Ingestible sensors | Ingestible sensors are microchips embedded in TB medications. After the dose is ingested, the ingestible sensor interacts with a patient’s gastric fluid and transmits a signal to an adhesive monitor worn by the patient. The monitor transmits pill-taking information to the patient’s smartphone, which transmits information to a server to allow HCPs to access dosing histories.37 38 | Costs not currently available. | Used in pilot studies in the USA.37 38 | Current ingestible sensor models do not have a reminder function; however, reminders can be sent to patients’ smartphones.38 | Ingestible sensors confirm actual medication ingestion since signal transmission happens when the ingestible sensor contacts gastric juices; however, patients must consistently wear the adhesive patch and have smartphone access.37 38 | HCPs use an online portal to access dosing histories compiled by the adhesive monitor and transmitted via smartphone to a server.37 38 | Triage strategies not defined in previous studies, but dosing histories may allow providers to identify non-adherent patients and provide differentiated care.38 |
DAT, digital adherence technology; DS TB, drug-susceptible tuberculosis; HCP, healthcare provider; LMIC, low-income and middle-income country; MDR TB, multidrug-resistant TB; SIM, subscriber identification model.