A) Optimal Medication Monitor(s) and Method of Retrieving  Adherence Record.

or



Alternative Communication Means are found in Alternative displays for Retrieval of Data from the Monitor This includes Retrieval of  Clinical Data on the Patient.

B) Other Dose Removal Monitors.






Clip Monitor for WHO's packaged medication (under development)

The Global Drug Facility at the World Health Organization assists in the distribution of packaged fixed dose combinations of TB medications (WHO's packaged medication). These preparations are given anywhere from two to five pills each day depending on the patient's weight.

Figure 1 shows the 4x7 package of the four drug combination caplets distributed by the WHO’s Global Drug Facility (GDF) that are used in the initial phase of therapy and how it can be broken into strips of 2, 3, 4, or 5 packages.
The Clip Medication Monitor is designed to dispense these strips of blister-packaged medication where each strip contains the proper number of individually packaged medication units for the prescribed drug regimen The clip arrangement shown in Figure 2 employs an array of clips in which each clip holds one strip of green blister-packaged two drug combination tablets for the continuation phase of therapy. As shown in Figure 2 the strips of packages are placed so each clip is between the first and second package of the strip. Each clip can hold a short strip of two packages or longer strips off three, four, or five packages.
Figure 1. Various ways to separate the 4 by 7 array of blister packages distributed by the Global Drug Facility to create strips with proper numbers of pills required for patients of different weights.
The array of clips is assembled into a carrier block, as shown in Figure 4 above. This protects the spring clips from mechanical damage and facilitates handling of the clips during manufacturing. This clip array is soldered to the electronic unit’s circuit board which is housed beneath a cover on the opposite side of the monitor from the medication compartment. Along with its other components, the electronics unit could incorporate a patient query button which the patient could press to find out if today’s medication had been removed, or not. Pressing the patient query button would cause a red/green LED to display a red light if medication should be taken and a green light if medication had already been taken. This LED could also be used to remind the patient to remove medication by flashing red until medication had been removed. A buzzer on the circuit board could also provide a reminder, as described in  Using Red LED and possibly a Buzzer to Alert Patient to Take Medication.

The buzzer can also be used to communicate the patient’s adherence record either 1) in the clinic, 2) when a community worker visits the patient, or 3) via a mobile phone, as described in:  Retrieval of the Adherence Record with Audible Tones in the Clinic or Transmitted to the Clinic by Mobile Phones.  

Figure 8 shows the other side of the clip monitor and indicates certain features.
Figure 2. Clips holding strips of 3 blister packaged tablets of the 2-drug combination used in the continuation phase of therapy. Note that the strips are placed so that the clips are between the first and second blister in the strip.
With an array of 30 clips similar to those shown in Figure 2, the monitor could be able to hold 30 doses of the  INH and RMP combination tablet used in the continuation phase of therapy (a 4-week supply plus 2 additional doses in case the patient is unable to be seen at a scheduled 4 week appointment).

A clip monitor containing 30 does of 5 tablets each is shown in Figure 5.
Figure 5. Clip monitor containing 30 strips of blister packaged tablets of the 2-drug combination used in the continuation phase of therapy. Each strip contains 5 tablets. Note that the strips are placed so that the clips are between the first and second blister in the strip, as indicated in Figure 2.
Clips
Unused Clips
By loading the strips of the thicker INH, RMP,PZA and EMB combination caplet used in the initial phase of therapy in every other clip, and with  the width and depth of the medication compartment appropriately chosen, this same monitor can hold 15 strips of  the larger caplets (a 2-week supply plus 1 additional dose). A clip monitor containing 15 does of 5 caplets each is shown in Figure 6.
Figure 6. Clip monitor containing 15 strips of blister packaged caplets of the 4-drug combination used in the initial phase of therapy. Each strip contains 5 caplets. Note that these thicker strips are held only in every other clip.
In Figures 5 and 6 the clip monitor is shown with its cover opened, as it would be when the patient is removing medication.  At other times, the monitor’s cover would normally be closed, as shown in Figure 7. The patient would be instructed not to put the packages from which medication had been removed back into the clips and would be given container, like a bag, to keep the empty packages. Since, the transparent cover would allow the patient to see how much medication remained in the monitor this should remind the patient to return for a refill of medication with or without opening the cover. A latch would hold the cover closed and tend to prevent unintended opening of the monitor.
Figure 7. Clip monitor with cover closed
Transparent cover
Cover latch
Figure 8. Clip monitor showing electronics unit cover
Battery compartment cover (locked)
Patient query button
Buzzer (beneath cover)
Red/ green LED
Transparent medication cover
Battery compartment lock
Electronics unit cover
Using a special key, the clinic worker can unlock the battery compartment in order to change the monitor’s batteries. Opening the battery compartment also provides the caregiver access to a USB connector (USB mini-B) which can be used to download information from a computer to the monitor or to upload compliance data from the monitor to a computer ( see: Direct Communication with Computers) . Opening the battery compartment may also provide access to a caregiver’s button.

Figure 9 shows the monitor with the battery compartment open.
Figure 9. Clip monitor with battery compartment cover open
Battery compartment cover (open)
USB connector
Caregiver’s button
Batteries
Battery contacts
Battery compartment key
Circuit board
5x7 red/green dot matrix display
If added functionality justified the additional cost, the single red/green LED could be replaced by a 5x7 red/green dot matrix display, as shown in Figure 10. Such a display could offer a number of functions activated by the caregiver’s button, as described in the following sections:

However, it is not likely that the additional cost would be justified since all of these functions except possibly the retrieval of clinical data can be readily achieved with the combination of a single red/green LED and a buzzer.
In order to keep track of which clips contain medication and which do not, the monitor’s microcontroller would maintain a list in which it would record the status of each clip.  When  the microcontroller first scanned the clips after the monitor was filled with medication, it would record the initial status of each clip in this list  as either empty (E) or filled (F). If the monitor had been filled with medication for the initial phase of therapy, half of the clips would be recorded as being filled (F) and half as being empty (E) since only every other clip could contain strips of the larger caplets.  If the monitor had been completely filled with medication for the continuation phase of therapy, all of the clips would be recorded as being filled (F).

The first time the microcontroller scanned the clips after the patient had removed a dose of medication, it would determine that one clip which had previously been filled (F) had become empty. It would , therefore, change the status of that clip in the list to empty (E); and medication removal would be recorded for the time and date when this removal event was detected.

Once a patient had removed medication, it is possible that the patient might reinsert a strip into an empty clip. While the patient would be instructed not to place an empty strip back into a clip from which medication had been removed the patient might do so. The patient might also reinsert a strip containing medication that had been accidentally removed. The electronic unit of the monitor would have no way of knowing whether the reinserted strip was empty or full, but would need to keep track of the reinsertion in order to respond appropriately if the reinserted strip was later removed. So, when it is first detected that a previously empty clip (E) is no longer empty, the recorded status of the clip would be changed to reinserted (R). If the reinserted strip contains medication, the package would in effect be a "pocket dose" which the patient might remove later to take the medication.  . (See section 3 b Retrieval of the Adherence Record with Audible Tones in the Clinic or Transmitted to the Clinic by Mobile Phones for how advanced removal creates a so called pocket dose).

Section 3 a  Using Red LED and possibly a Buzzer to Alert Patient to Take Medication describes how an LED is illuminated at the beginning of each day to remind the patient to take medication and is turned off for the remainder of the day when a medication package is removed. When a reinserted strip is removed from a clip whose status was R, the reminder LED would be turned off for the remainder of the day as occurs when any strip is removed. If the strip contained pills this is obviously the correct instruction for the patient. If the strip had no pills the patient would see that the strip was empty and would logically remove another strip that contained pills and the microprocessor would record that the strip that contained pills had been removed.

To save power it would be possible to enable the microcontroller to scan the clips only when the cover was opened. To make sure the cover was closed at all times except when the patient was removing medication the cover could have a spring in it’s hinge. However, the cost of the spring mechanism , along with a switch to sense when the cover was open, might outweigh the benefit of less power consumption.
Figure 3. Clips holding strips of 3 blister packaged caplets of the 4-drug combination used in the initial phase of therapy. Here again, the strips are placed so that the clips are between the first and second blister in the strip.
Note that these larger packages are only placed in alternate clips.
Note that the clips shown in Figure 2 are spaced just far enough apart to accommodate a strip containing  tablets of the 2-drug combination to be placed in each clip. This spacing facilitates the design of the smallest possible dispenser for, say, a 4 week supply of these tablets. However, the 4-drug combination caplets used in the initial phase of therapy are larger than the 2-drug combination tablets. So, it would only be possible to place a strip of these larger caplets in every other clip, as shown in Figure 3.  This is appropriate since the patient should be seen by the clinic or by a community worker at least every 2 weeks during the initial phase of therapy, but would usually be seen at 4 week intervals during the continuation phase.
Figure 10. Clip monitor with 5x7 red/green LED dot matrix display
rather than a single red/green LED
Caregiver’s button
Recording Medication Removal:
Design Features of a Clip Monitor:
As shown in Figure 4, each clip consists of 2 spring leaves; and each of these spring leaves incorporates an extension (a “pin”) by which it is soldered to a pad on the monitor’s circuit board. When a clip is empty, its 2 spring leaves make contact completing an electrical circuit between the clip’s 2 pins. When a clip holds a strip of packaged medication, its 2 spring leaves are held apart by the medication package; and the circuit between  the clip’s 2 pins is open.

To sense electrical continuity through the clips, the electronic unit periodically connects each clip into a circuit . If a strip of packages is being held in a clip, electricity will not pass, but when the strip is removed electricity will pass.  If electricity fails to pass through a clip at a first point in time, like 10:00 AM, and passes at a second point in time, like 10:05 AM, this demonstrates that the package was removed from the clip between these two times.
Figure 4. Clip details.
Pins for soldering clip spring leaves to circuit board
Clip Array body
Clip Spring Leaves