TY - JOUR
AU - Redic, Kimberly, A
AB - investigational drugs, oral chemotherapy, patient education, patient instruction, safe administration The use of oral medications for the treatment of cancer has increased significantly in recent years.1,2 A 2008 National Comprehensive Cancer Network task force report on oral chemotherapy included an estimate that more than 25% of chemotherapy drugs in the pipeline were for oral administration.2 This percentage is expected to grow, causing an increase in the number of oral chemotherapy medications (OCMs) used in clinical trials.3 The growth is also reflected in the number of new drug applications for OCMs approved for marketing by the U.S. Food and Drug Administration (FDA). From 2015 through 2017, 19 of the 29 (66%) new molecular entities approved by the FDA Center for Drug Evaluation and Research for the treatment of cancer were oral medications.4–6 As researchers continue to develop more OCMs, medication administration responsibilities can be expected to shift from healthcare provider–supported infusion facilities to research subject self-administration at home. These responsibilities include the administration of the correct dose at the right time in relation to food and other medications; proper medication preparation, storage, and disposal; and the identification and management of interactions and adverse effects. Because the majority of these medications are considered hazardous,7 their use introduces new challenges that include the safe handling of these oral medications in the home by nonhealthcare workers. Research subjects and caregivers are now faced with complex oversight and management of OCMs, which increases the potential risks of medication errors, poor adherence, inappropriate adverse effect management, and contamination. Participation in a clinical trial that includes an oral investigational medication introduces additional challenges. Unlike marketed medications, investigational medications do not come with a manufacturer’s label or an information handout targeted to study subjects. Additionally, information on these medications is more difficult to locate on commercially available sources or the Internet. Therefore, information on investigational medication use and storage is not readily available. Subjects participating in clinical trials are presented and provided with an informed consent form. Although potential adverse effects and drug interactions are included in the consent process, the Code of Federal Regulations and FDA guidance on informed consent do not require or suggest that instructions on medication storage, handling, and disposition or information that is specific to adherence while participating in a trial be included in the consent process.8,9 Labels that are placed by the pharmacy on the medication containers may include administration and storage information, but this information may be abbreviated and lack detail. As the development of OCMs continues to increase, the need for study subject counseling and education in the investigational setting becomes imperative to ensure that trial data are accurate and safety is appropriately addressed. During a clinical trial, monitoring for adverse effects and adherence are crucial for the validity and reliability of study results. Therefore, it is important that study subjects are provided with clear instructions on when to report untoward effects. Correct and completed medication administration is of special importance because administration or dosing errors and issues with adherence may result in drawing erroneous conclusions and making inappropriate dose changes. In a risk assessment study of 5 OCMs, the identified key vulnerabilities included patient education about drug handling and adverse effects, prescription writing, patient self-administration and medication adherence, and failure to monitor and manage toxicities.10 One of the recommended risk-reduction strategies was making improvement in patient education and including a written document for all OCM treatment. The American Society of Clinical Oncology (ASCO), the Oncology Nursing Society (ONS), and the American Society of Health-System Pharmacists have published guidelines and recommendations on safe administration of FDA-approved OCMs.11,12 These include a list of items that should be included in the education material. The ASCO/ONS standards include a statement that patient education material must be written in or presented at a level that is appropriate for the patient’s reading level and literacy and patient–caregiver understanding. In 2014, the Hematology/Oncology Pharmacy Association released a paper calling for best practice standards within an investigational drug service.13 The paper specifically highlights the need for medication counseling for study subjects receiving investigational medications, including medication handling and safe storage. In addition, the authors state, “This is especially crucial for patients receiving oral investigational medications.” Currently, pharmaceutical companies, medical institutions (i.e., hospitals and clinics), and professional organizations prepare medication information handouts for commercial OCMs that can be included in patient counseling sessions. For example, the Association of Community Cancer Centers, Hematology/Oncology Pharmacy Association, National Community Oncology Dispensing Association, and ONS have created oral chemotherapy education sheets to provide information to patients with cancer and caregivers.14 Templates for creating brochures for the preparation, administration, and handling of OCMs were published in 2014.15 These brochures focused on the manipulation of solid dosage forms for administration to patients with swallowing difficulties, but they do not address the specific issues for investigational medications. Other than informed consent documents, study-subject education handouts are not readily available for investigational medications. Creating medication-specific handouts for investigational drugs may be restricted by the proprietary nature of and confidentiality agreements established for drugs in development. However, the increased needs, challenges, and risks associated with the use of oral investigational medications call for the provision of detailed counseling, including, written instructions in plain language to study subjects and/or caregivers who administer OCMs at home. To fulfill the need, a general handout detailing specific requirements associated with the use of investigational OCM was developed ( appendix). This handout can be used while counseling study subjects who receive investigational OCMs. Specific information related to the importance of adherence in the context of clinical trials, as well as information about placebo controls, the use of a medication diary, hazardous drug handling precautions, and storage in the original container are included. Reference to the informed consent document is included, as is a space to include study-team contact information. This document may be provided to a subject by the study team at the time of enrollment, included by the pharmacy dispensing the investigational medication, or provided as a general handout in a patient-education resource center. As with other documents provided to subjects who participate in clinical trials, clinicians and study teams must consult with their institutional review boards on the best way to make this handout available to study participants before distributing it by any of these or other means. The material has been edited for plain language following the guidelines in the Centers for Medicare and Medicaid Services Toolkit for Making Written Materials Clear and Effective and scored 85% on the Patient Education Materials Assessment Tool for printable materials for understandability and 80% for actionability.16,17 Consequently, it may be valuable to reinforce content verbally with some study subjects or limit use to provision at the time of obtaining consent, when the content can be reviewed in person with the subject. Providing a quick, easy-to-read handout can enable healthcare providers such as pharmacists and research associates to comply with their important good clinical practice responsibilities.18 Acknowledgments: The authors thank Ruti M. Volk, M.S.I., AHIP, Patient Education and Health Literacy Program Lead at Michigan Medicine, for plain-language recommendations and review. Disclosures: The authors have declared no potential conflicts of interest. The Frontline Pharmacist column gives staff pharmacists an opportunity to share their experiences and pertinent lessons related to day-to-day practice. Topics include workplace innovations, cooperating with peers, communicating with other professionals, dealing with management, handling technical issues related to pharmacy practice, and supervising technicians. Readers are invited to submit manuscripts, ideas, and comments to AJHP, at ajhp@ashp.org. References 1. McCue DA , Lohr LK , Pick AM . Improving adherence to oral cancer therapy in clinical practice . Pharmacotherapy. 2014 ; 34 : 481 - 94 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Weingart SN , Brown E , Bach PB et al. NCCN task force report: oral chemotherapy . J Natl Compr Canc Netw. 2008 ; 6 ( suppl 3 ): S1 - 14 . Google Scholar Crossref Search ADS PubMed WorldCat 3. Buffery , D . Innovation tops current trends in the 2016 oncology drug pipeline . Am Health Drug Benefits . 2016 ; 9 : 233 - 238 . Google Preview WorldCat COPAC 4. Food and Drug Administration . Novel drug approvals for 2015. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm430302.htm ( accessed 2018 Sep 22 ). 5. Food and Drug Administration . Novel drug approvals for 2016. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm483775.htm ( accessed 2018 Sep 22 ). 6. Food and Drug Administration . Novel drug approvals for 2017. https://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm537040.htm ( accessed 2018 Jun 16 ). 7. National Institute for Occupational Safety and Health . NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016 https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf ( accessed 2019 Oct 5 ). 8. U.S. Food and Drug Administration . Code of Federal Regulations Title 21, Part 50, Subpart B, Section 50.25 (April 1, 2018) . https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.25 ( accessed 2019 Jan 26 ). 9. Food and Drug Administration . Informed consent information sheet: guidance for IRBs, clinical investigators, and sponsors (July 2014) . https://www.fda.gov/RegulatoryInformation/Guidances/ucm404975.htm ( accessed 2019 Jan 26 ). 10. Weingart SN , Spencer J , Buia S et al. Medication safety of five oral chemotherapies . J Onco Pract. 2011 ; 7 : 2 - 6 . Google Scholar Crossref Search ADS WorldCat 11. Neuss MN , Polovich M , McNiff K et al. 2013 Updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy . J Oncol Pract. 2013 ; 9 : 5s - 13s . Google Scholar Crossref Search ADS PubMed WorldCat 12. Goldspiel B , Hoffman JM , Griffith NL et al. ASHP guidelines on preventing medication errors with chemotherapy and biotherapy . Am J Health-Syst Pharm. 2015 ; 72 : e6 - 35 . Google Scholar Crossref Search ADS PubMed WorldCat 13. Amin SR , Lee JS , Avila JG et al. HOPA investigational drug service best practice standards. http://www.hoparx.org/images/hopa/resource-library/professional-tools/HOPA16_IDS_Guidelines.pdf. ( accessed 2018 Aug 19 ). 14. OralChemoEdSheets.com, the Patient and Healthcare Providers Resource. https://www.oralchemoedsheets.com/index.php/sheet-library ( accessed 2019 Oct 5 ). 15. Siden R , Kem R , Ostrenga A et al. Templates of patient brochures for the preparation, administration and safe-handling of oral chemotherapy . J Oncol Pharm Practice. 2014 ; 20 : 217 - 24 . Google Scholar Crossref Search ADS WorldCat 16. Centers for Medicare and Medicaid Services . Toolkit for making written material clear and effective ( 2012) . https://www.cms.gov/Outreach-and-Education/Outreach/WrittenMaterialsToolkit/index.html ( accessed 2018 Sep 21 ). 17. PEMAT for Printable Materials (PEMAT-P) (October 2013). Rockville, MD : Agency for Healthcare Research and Quality . http://www.ahrq.gov/professionals/prevention-chronic-care/improve/self-mgmt/pemat/pemat-p.html ( accessed 2018 Sep 21 ). COPAC 18. U.S. Food and Drug Administration , Department of Health and Human Services. International Conference on Harmonisation: good clinical practice consolidated guideline . Fed Regist. 1997 ; 62 : 25692 - 709 . www.gpo.gov/fdsys/pkg/FR-1997-05-09/pdf/97-12138.pdf ( accessed 2019 Jan 26 ). WorldCat Appendix—Handout for patients receiving investigational oral chemotherapy Oral Medications Used in Clinical Studies Medications used in clinical studies include: Medications that have not yet been approved by the U.S. Food and Drug Administration (FDA). Medications that have been approved by the FDA for certain health conditions and now being tested for safety and effectiveness to treat new or different health conditions. You are participating in a clinical study and are taking a study medication by mouth. The name of the medication that you are taking is: _________________________ and the study number is: ____________________. Here is some important information on participating in a study and how to safely take, handle, and store the study medication: What do I need to know about being in a clinical study? Your study medication may be available to patients with other diseases and information on its use may be available in ads and on websites. However, because you are taking this medication as part of your participation in a clinical study, you must follow the instructions that the study team gave you. Some clinical studies use a “control group” to determine if the investigational treatment is effective. This means that you may receive the standard treatment or a placebo instead of the investigational medication. ◦ A placebo is an inactive tablet, capsule, or other treatment. In clinical studies with control groups or placebos, you and your doctor may not know which medication you are taking. Even if you may be taking a placebo, it is important to take your study medication exactly as directed. The “Informed Consent” document you signed at the beginning of the clinical study has more information about your study medication and how to contact the study team. How should I take the study medication? Take your study medication exactly as instructed. This will ensure your safety and allows the study team to receive accurate information from your participation. If you are taking medications by mouth, it is important that you swallow each tablet or capsule whole. Do not chew, crush, or open the medication unless the study team tells you that you can do that. If you cannot swallow the study medication, contact your study team about other ways to take your medication. If you miss a dose or vomit up a dose, check the instructions that the study team gave you or contact the study team as soon as you can to find out what you should do. If you receive a medication diary or a study log, fill it out completely and accurately. In the medication diary, be sure to list any doses that you missed or vomited and any side effects that you felt. Bring the medication diary or your log with you to the next hospital or clinic visit. How do I store the medication? Keep the study medication in its original container. Do not transfer the medication to another container or medication box. Store your medication in a safe place, away from other family medications or food, and out of the reach of children and pets. Check the medication label to see if it requires special storage, such as refrigeration or protection from light. If your medication needs to be stored at room temperature, store it away from excessive heat and moisture and out of direct sunlight. Do not store your medication in the bathroom. If your medication needs to be stored in the refrigerator, use a zip-top bag to keep it away from food. If the medication needs to be protected from light, place it in a brown paper bag or a dark cabinet or closet. When you travel, do not store the medication in the car to avoid exposure to extreme temperatures. When you fly, take the medication in your carry-on luggage to ensure that the temperature is controlled and to avoid losing the medication. What are some important tips to study participants? Be sure to bring all bottle(s) or container(s) (including empty containers) to each clinic visit or if you are admitted to the hospital. Do not dispose of any study medication yourself. Study medications may interact with other medications, supplements, or herbal products. Include your study medication in the list of medications you take at home. Tell your pharmacist and primary care doctor about your study medication so that they will have an accurate list of all your medications. How should I protect myself if the medication is considered hazardous? Wash your hands before and after handling study medications. Check with the study team to determine if it is necessary to wear gloves while handling the medication. If you spilled the medication on your skin, remove contaminated clothing, wash the area with soap and a large amount of water, and contact the study team. Do not wash soiled clothes with your other laundry. If the medication got into the eyes, flush with water for at least 15 minutes and contact the study team. If you are instructed to dissolve the study medication in liquid or mix it with food, check with the study team to see if you need to cover the work area to protect from contamination and to use disposable dishes and utensils. If you have a low-flush or high-efficiency toilet, close the lid and flush twice to ensure all body waste is removed. When do I need to contact the study team? If you accidently spilled the study medication on your skin or the medication got into your eye. If you dropped a pill or misplaced the medication bottle. Before starting a new medication (including over-the-counter medications and herbal supplements). If you feel that you are having side effects from taking the study medication. If you have any questions or concerns about the study or study medication. If you are not sure how to take the study medication. Whom can I contact? During office hours contact: _________________________ _________________________ Name  Phone After hours contact: __________________________________________________ Where can I find more information on clinical studies or study medications? https://www.cancer.gov/about-cancer/treatment/clinical-trials http://www.fda.gov/forpatients/clinicaltrials/default.htm Notes: ____________________________________________________ __________________________________________________________ __________________________________________________________ __________________________________________________________ Disclaimer: This document is for informational purposes only and is not intended to take the place of the care and attention of your personal physician or other professional medical services. Talk with your doctor if you have questions about individual health concerns or specific treatment options. This material is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) For the full license visit: https://creativecommons.org/licenses/by-nc-sa/4.0/ © American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Handout for research subjects receiving investigational oral chemotherapy
JF - American Journal of Health-System Pharmacy
DO - 10.1093/ajhp/zxz239
DA - 2019-12-02
UR - https://www.deepdyve.com/lp/oxford-university-press/handout-for-research-subjects-receiving-investigational-oral-67ii6gxt3Q
SP - 2009
VL - 76
IS - 24
DP - DeepDyve
ER -