Concomitant Meds - C.Dee

Concomitant Medications

Clinical Trials Office

Contents

• What are Con-Meds?
• Definitions
• Accuracy Matters
• Patient Eligibility
• Challenges

What are Concomitant Medications?

Medications taken by a study participant in addition to the drug(s) under investigation. Can include all the following:

• Prescription medications
• Over-the-counter (OTC) medications
• Dietary supplements
• Biological products

Concomitant Medications (Con-Meds)

• Con-meds may be taken for the same indication as the study drug(s) or for other indications
• Con-meds should be verified and updated at every visit
• Information pertaining to con-meds may be obtained from the patient, EMR, outside records, and family members

Con-Meds Cont.

Definitions

• Intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease
• Intended to affect the structure or any function of the body

Drug

Generic Name

(Describes the drug substance).

This Photo by Unknown Author is licensed under CC BY-ND

This Photo by Unknown Author is licensed under CC BY-SA-NC

Trade Name

(The advertised brand name under which the drug is sold).

Which Do I Use: Generic or Trade Name?

Sponsors may specify whether to utilize generic or trade names

When the sponsor does not specify either may be utilized

The generic name is generally preferred because of its specificity

The reason a medication is used:

• Treatment
• Prophylaxis
• Diagnosis
• Mitigation
• Cure

Indication

Issues with Indications

The terminology used for the medication indication should match as close to verbatim as possible the historical condition or adverse event being treated.

If the medication is not utilized for an adverse event or historical condition, then the specific intent must be described, i.e., prophylaxis, diagnosis, mitigation, or cure.

When the medication indication and adverse event terminology do not match it requires time-consuming reconciliation by the data team.

Treatments or actions designed to preserve health

• Treatments or actions designed to preserve health

Prophylaxis

• An antibiotic taken prior to surgery to prevent a possible infection
• Taking an antibiotic for a prolonged period following the resolution of an infection in order to prevent reoccurrence
• Vaccines

Examples of Prophylaxis Medications

• When a con-med uses prophylaxis as the indication, there is not normally an adverse event associated with it.
• For example, Zofran taken prophylactically to prevent treatment induced nausea would not have nausea listed as an adverse event
• Zofran taken when nausea has occurred would have nausea listed as an adverse event.

Notes about Prophylaxis

• As needed or required

PRN

• Denotes the quantity of a medication to be taken at one time or at stated intervals (i.e. 1tablet, 1 tsp, 500mg)

Dose or Dosage

• How the medication is introduced into the patient’s body (i.e., orally, rectally, topically, intramuscular, subcutaneous)

Route of Medication Administration

Different Routes of Administration

• How often a medication is used or taken (i.e. once daily, two times a day)

Frequency

• Term used to denote a medication’s amount (i.e. mg, mcq, ml, kg/ml)

Medication Unit

• Documentation should include medication, dose, route, frequency, and indication.
• When the medication, dose, route, frequency, or indication changes the research nurse/coordinator is responsible for recording the new information and listing a stop date and a start date
• The start/stop date of a medication is the timeframe in which the medication was or is being used
• The sponsor may specify how dates are to be recorded. If not, state them in a complete month/day/year or day/month/year format. Always try to get the complete date(s) of use of a medication through communication with the subject rather than an estimate. If the patient cannot recall the day/month enter 01/01/year.

Notes about Documentation

Example of Documentation with Dose Change

• Ampicillin 250 mg (Dose) Orally (Route) Four times a day (Frequency) Sinus Infection (Indication) Start Date: 10/01/22 Stop Date: 10/05/22
• Ampicillin 500mg (Dose) Orally (Route) Four times a day (Frequency) Sinus Infection (Indication) Start Date: 10/05/22

Patient Erin Pickles is taking: Ampicillin 250mg by mouth four times a day for a sinus infection starting date 10/01/22 On 10/05/22 she is still febrile, so the provider changes it to: Ampicillin 500mg by mouth four times a day

Example of Documentation with Route Change

• Demerol 50mg (Dose) Intravenous (Route) Every 4 hours as needed (frequency) Pain (Indication) Start Date: 9/20/22 Stop Date: 9/22/22
• Demerol 50mg (Dose) Intramuscular (Route) Every 4 hours as needed (frequency) Pain (Indication) Start Date: 9/22/22

Patient Erin Bubbles is receiving: Demerol 50mg IV every 4 hours for pain prn starting on 09/20/22 On 9/22/22 her pain is improving so the provider changes it to: Demerol 50mg IM every 4 hours for pain prn

Example of Indication Change

Patient Erin Giggles is taking: Zofran 8mg orally every 8 hours for the prevention of chemotherapy induced nausea starting on 10/01/22 On 10/05/22 she experiences nausea, and her provider changes it to: Zofran 8mg orally every 8 hours prn nausea Don’t forget an adverse event of nausea needs to be added to the AE log

• Zofran 8mg (Dose) Orally (Route) Every 8 hours (Frequency) Prophylaxis for the prevention of chemotherapy induced nausea (Indication) Start Date: 10/01/22 Stop Date: 10/05/22

• Zofran 8mg (Dose) Orally (Route) Every 8 hours as needed (Frequency) Nausea (Indication) Start Date: 10/05/22

• Good Clinical Practice (GCP) regulations mandate that investigators pay attention to con-meds used by study participants
• Inaccurate con-med reporting can lead to faulty conclusions regarding the safety and efficacy of the study drug(s)
• Lack of consistency makes it difficult to correlate the data with the primary endpoints of the study
• Con-meds may indicate a patient’s condition that affects the pharmacokinetics of the study drug(s)

Why Accuracy of Con-Meds Matters

A good con-med analysis will highlight issues to be considered for contraindication, for inclusion on label, or for further investigation in later stage studies.

• Almost 80% of clinical trials fail to meet patient enrollment timelines
• This delay means fiscal budgets are stressed and potentially life-saving treatments are often severely delayed
• Medication-related exclusion criteria are among the most common barriers to enrollment in clinical trials
• 54.1% of trials to have at least one medication-related exclusion criterion
• A recent review of Phase 1 cancer trials noted that nearly 100% of study participants in the trials studied used concomitant medications

Impact of Con-Meds on Patient Eligibility

The Good News

In most cases, acceptable solutions (con-med discontinuation or substitution) may be found for patients taking con-meds either prohibited by a study protocol or having potential interactions with the investigational drug.

• Patient is a poor historian
• Medications listed in the EMR, provider note, and research nurse note do not match
• No adverse event listed for con-med
• PRN medications are continuous, even if used for different indications
• No start/stop dates listed
• New entries not made for change in route, frequency, dosage, and/or indication

Challenges In Con-Med Tracking

Food for Thought

• With sponsors facing tremendous financial pressures to run their trials on-time and on-budget, we need to recognize the importance of concomitant medications in meeting patient enrollment timeline
• Tracking concomitant medication data correctly and routinely across sites allows the appropriate conclusions to be drawn
• Accurate con-med tracking can reduce the overall cost of healthcare and speed the delivery of life-saving therapies

Questions?

References

Centers for Disease Control and Prevention, (2022). Health literacy: Medications. (Obtained October 2022). https://www.cdc.gov/healthliteracy/researchevaluate/medications.html Lord, S., Hall, P.S., & Seymour, M.T. (2010). Concomitant medication in cancer patients: Should we be more active in their management? Ann Oncol, 21(2), 430. doi: 10.1093/annonc/mdp539 McGahey, K.E., & Weiss, G.J. (2017). Reviewing concomitant medications for participants in oncology clinical trials. American Journal Health Syst Pharm, 74(8), 580-86. doi: 10.2146/ajhp151052. National Cancer Institute, (2018). Concomitant medications. (Obtained October 2022). https://wiki.nci.nih.gov/display/CRF2/Concomitant+Medications