Monitoring at the pharmacy is an integral part of on-site monitoring and it is very important to ensure that the treatments under study have been properly allocated and administered/taken by the patient, both for patient safety and relevance of the data collected.

You are CRA on a study involving a drug and you have to go and monitor the pharmacy?

Here are some tips to make your visit to the pharmacy a success.

The center, you shall contact

When you organize your visits on site, I advise you to contact the pharmacy first. Indeed, the time to get an appointment in some pharmacies is sometimes very long.

Ideally, consider making an appointment for the next visit whenever you are on site, subject to modification if the CSC and/or investigator are not available afterwards.

Ask the center to prepare the study workbook, temperature readings as well as treatments returned by the patients. Indeed, the pharmacy must keep the treatments under study for monitoring, it is you who will give the authorization to destroy the treatments once you have carried out the quality control.

However, if the treatment under study is a cytotoxic product requiring reconstitution, then the center will be able to destroy the treatment before your visit, in accordance with the recommendations of the French Society of Oncologic Pharmacy which we have already spoken to you in the article Planet oncology.

Prepare your visit, you shall do

As with any visit, monitoring at the pharmacy is prepared. Begin by reviewing the previous monitoring reports and record any problems identified during the previous visit and not resolved at the time you are preparing the visit. You will have to treat them when you come to the site.

Then, make an inventory of what you should find on site:

• What data were monitored during the previous visit and what data have yet to be reviewed? To do this, simply consult the previous monitoring report.
• How many patients have received study treatment since the last visit?To retrieve these data, simply check the list of patients newly enrolled or receiving the treatment under study via the electronic CRF or through the information provided by the center.
• What treatments were given to patients? If your study is randomized, you may have access to the treatment numbers issued for each patient. It may be useful to print it in order to check more easily the treatments issued on site.
• Has the center received any new study treatments since the last visit?

To do this, consult the listings of the IWRS or the IVRS or get closer to your project manager in order to obtain it if you do not have access to this kind of tools.

Finally, print the blank forms of the study: table of global accounting of the treatments, table of accounting by patient… in case it might be missed in the center.

The accounting of the treatment, you shall do

Once on site, the pharmacist will provide you with the workbooks of the study containing the accounting records of the treatment. Some pharmacies have their own procedure and use their own accounting files (by hand or computer), if the promoter agrees, of course. Others agree to use the study forms. Normally, this was discussed during the implementation.

Once these forms are in your possession, you will have to check:

• If the treatments delivered to the patients and indicated on the accounting sheets correspond to the treatments attributed during the randomization. To do this, you will check on the IVRS/IWRS report the nature and dose of treatment allocated (if your study is in open and/or includes several treatments under study) and the batch number of the treatment. This must correspond to what is indicated on the accounting sheets, any prescriptions, as well as the labels of the treatments kept by the center.
• If the global accounting is correct. For this you will check the balance between the treatments received and the treatments delivered indicated on the accounting sheet with the number of treatments actually on site.
• In addition, verifies that the expiry date of treatments already dispensed was not exceeded at the time they were provided to the patient. In addition, verifies that the remaining treatment stock is not outdated.

If this is the case, the center should have placed the treatments in quarantine pending instructions: either the treatment will be destroyed on site or returned to the promoter for destruction. In some cases, the promoter may request re-labelling of treatments. In this case, make sure that the procedure has been followed and adequately documented.

In case of destruction on site, the center must provide you with a certificate of destruction as well as the destruction procedure for filing in the workbook of the study as well as in the TMF.

• If the patient accounting is correct. To do this, you will check if the deliveries are in agreement with the protocol as well as the patient’s compliance and/or the good delivery of the injectable treatment.
• If the people who received, dispensed or reconstituted a treatment under study were well trained in the protocol (presence at the implementation or documented training on a training form), declared on the task delegation sheet and whose CV dated and signed has been recovered.

If you have any questions or doubts about the data that have been reported, discuss it with the pharmacist to explain what happened and understand the situation.

In case of deviation from the protocol, it must be documented. Prepare a Note to File. This is a note indicating the situation as well as the cause. Requests the pharmacist to review and, if appropriate, date and sign. Take a copy of it and place it in the study workbook.

Also think of re-training the pharmacist and his team in order to prevent the situation from recurring in the future.

Finally, in case of serious deviation, contact your project manager immediately so that he/she tells you the procedure to follow.

Counting the treatments, you shall do

If your study is about a drug in the form of tablets, capsules, coated capsules … you will have to count the number of tablets that the patient brought back to the site to check the accounting of pharmacy treatments and especially the adherence of patient. When patients return the treatments, the center will report the return date as well as the number of tablets on the patient accounting form. That’s the number you’ll have to check.

To do this, you need the date on which the patient started treatment, the rate of taking and the date the patient stopped the treatment. If your study includes a patient follow-up record, it will be easier to know these dates.

For example, if your patient started treatment on 02/11/2016, stopped treatment on 01/12/2016 and treatment should be taken twice a day, the patient should have taken 29 days x 2/day = 58 tablets.

If a treatment box contains 70 tablets, then you should find: 70 – 58 = 12 tablets on site.

Then, you simply calculate the compliance by balancing the planned tablets and the tablets actually found on site.

Let’s take again our example, the patient brought back 15 tablets. The compliance is thus 12/15 = 80%.

Do not forget to compare this calculated compliance with the source data: have there been documentation of the discontinuation of treatment? Was there an adverse event requiring discontinuation? If you do not find information in the source data, talk to the center CSC, he or she should get closer to the patient to find out what happened. Indeed, perhaps there was an event motivating the discontinuing of treatment which the patient did not talk to the investigator.

The preparation sheets, you shall ask

If your study involves injectable treatment, you should check the product preparation sheets. Indeed, you must ensure that the dosages have been respected and that the reconstitution has been carried out in agreement with the investigator brochure.

The temperature reading, you shall consult

Finally, treatments under study should be stored at a certain temperature that you will find in the investigator brochure. Your role is to check that there was no temperature excursion. To do this, you will ask the center to provide you with temperature readings. Either the center uses a temperature recorder disk, a thermometer with minimum and maximum temperatures with manual or computerized readings. The center should allow you to view the temperature records since receiving the treatment (or the last monitoring visit if this has already been verified) and until the destruction or return of the treatment. Do not forget to ask for a photocopy for the TMF.

Beware, some centers refuse to provide photocopies of temperature reading, in which case the study pharmacist must produce a dated and signed certificate stating that there was no temperature excursion during the given period. Ask the pharmacy to prepare a certificate for each monitoring visit.

When you come, you identify a temperature excursion, what to do? In general, a procedure to be implemented in case of temperature excursion is indicated in the study manuals, make sure that it has been followed. However, immediately notify your project manager if the pharmacy has not quarantined the treatment.

The study workbook, you shall review

The study workbook that is located at the pharmacy is just as important as the workbook that is in the department. Remember to check it regularly.

After the visit, your report you shall write

Remember to document what you saw during the visit, it will be easier for you to prepare your visit afterwards. For example, if you have reviewed the temperature readings, indicate the starting date and ending date of the readings you reviewed.

In addition, it is preferable to indicate the quantity, nature, batch numbers and expiry date of the treatments that you saw on site, whether they were administered or not. This will give you easy access to information in case of questions.

Obviously, document deviations from the protocol as well as other problems identified during the visit.

Here are my few tips for making a successful pharmacy visit. Pharmacy is one of the pillars of a successful clinical trial. Each pharmacy has its own procedures and is more or less accustomed to clinical trials, make sure to communicate with the pharmacist and pharmacy preparers to identify any malfunction and propose solutions.

Do you make visits to the pharmacy? Share your experience in the comments.

Written by Sophie Hammer