Appl Clin Inform 2021; 12(04): 845-855
DOI: 10.1055/s-0041-1735182
Review Article

Effect of Electronic Prescribing Compared to Paper-Based (Handwritten) Prescribing on Primary Medication Adherence in an Outpatient Setting: A Systematic Review

David Aluga
1   School of Health and Life Sciences, Teesside University Middlesbrough, Middlesbrough, United Kingdom
Lawrence A. Nnyanzi
1   School of Health and Life Sciences, Teesside University Middlesbrough, Middlesbrough, United Kingdom
Nicola King
2   Student and Library Services, Teesside University Middlesbrough, Middlesbrough, United Kingdom
Elvis A. Okolie
1   School of Health and Life Sciences, Teesside University Middlesbrough, Middlesbrough, United Kingdom
Peter Raby
1   School of Health and Life Sciences, Teesside University Middlesbrough, Middlesbrough, United Kingdom
› Author Affiliations


Background Electronic prescriptions are often created and delivered electronically to the pharmacy while paper-based/handwritten prescriptions may be delivered to the pharmacy by the patients. These differences in the mode of creation and transmission of the two types of prescription could influence the rate at which outpatients fill new prescriptions of previously untried medications.

Objectives This study aimed to evaluate literatures to determine the impact of electronic prescribing compared with paper-based/handwritten prescribing on primary medication adherence in an outpatient setting.

Methods The keywords and phrases “outpatients,” “e-prescriptions,” “paper-based prescriptions,” and “primary medication adherence” were combined with their relevant synonyms and medical subject headings. A comprehensive literature search was conducted on EMBASE, CINAHL, and MEDLINE databases, and Google Scholar. The results of the search were screened and selected using predefined inclusion and exclusion criteria. The Critical Appraisal Skills Program (CASP) was used for quality appraisal of included studies. Data relevant to the objective of the review were extracted and analyzed through narrative synthesis.

Results A total of 10 original studies were included in the final review, including 1 prospective randomized study and 9 observational studies. Nine of the 10 studies were performed in the United States. Four of the studies indicated that electronic prescribing significantly increases initial medication adherence, while four of the studies suggested the opposite. The remaining two studies found no significant difference in primary medication adherence between the two methods of prescribing. The variations in the studies did not allow the homogeneity required for meta-analysis to be achieved.

Conclusion The conflicting findings relating to the efficacy of primary medication adherence across both systems demonstrate the need for a standardized measure of medication adherence. This would help further determine the respective benefits of both approaches. Future research should also be conducted in different countries to give a more accurate representation of adherence.

Protection of Human and Animal Subjects

This is a secondary study that synthesized the findings of original studies. No human or animal subjects were recruited.

Supplementary Material

Publication History

Received: 16 March 2021

Accepted: 15 July 2021

Article published online:
25 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Fischer MA, Stedman MR, Lii J. et al. Primary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med 2010; 25 (04) 284-290
  • 2 World Health Organization. Adherence to Long-term Therapies; Evidence for Action. Geneva, Switzerland: World Health Organization; 2003
  • 3 Hubbard TE. et al. Ready for Pick-Up: Reducing Primary Medication Non-Adherence, A New Prescription for Health Care Improvement. The Network for Excellence in Health Innovation, A NEHI. Issue Brief 2014. Available at:
  • 4 Adams AJ, Stolpe SF. Defining and measuring primary medication nonadherence: development of a quality measure. J Manag Care Spec Pharm 2016; 22 (05) 516-523
  • 5 Shah NR, Hirsch AG, Zacker C. et al. Predictors of first-fill adherence for patients with hypertension. Am J Hypertens 2009; 22 (04) 392-396
  • 6 Hugtenburg JG, Timmers L, Elders PJM, Vervloet M, van Dijk L. Definitions, variants, and causes of nonadherence with medication: a challenge for tailored interventions. Patient Prefer Adherence 2013; 7: 675-682
  • 7 Wroe AL. Intentional and unintentional nonadherence: a study of decision making. J Behav Med 2002; 25 (04) 355-372
  • 8 Lowry KP, Dudley TK, Oddone EZ, Bosworth HB. Intentional and unintentional nonadherence to antihypertensive medication. Ann Pharmacother 2005; 39 (7-8): 1198-1203
  • 9 Lehane E, McCarthy G. Intentional and unintentional medication non-adherence: a comprehensive framework for clinical research and practice? A discussion paper. Int J Nurs Stud 2007; 44 (08) 1468-1477
  • 10 Clifford S, Barber N, Horne R. Understanding different beliefs held by adherers, unintentional nonadherers, and intentional nonadherers: application of the Necessity-Concerns Framework. J Psychosom Res 2008; 64 (01) 41-46
  • 11 Jani YH, Barber N, Wong ICK. Paediatric dosing errors before and after electronic prescribing. Qual Saf Health Care 2010; 19 (04) 337-340
  • 12 Abramson EL, Barrón Y, Quaresimo J, Kaushal R. Electronic prescribing within an electronic health record reduces ambulatory prescribing errors. Jt Comm J Qual Patient Saf 2011; 37 (10) 470-478
  • 13 Shawahna R, Rahman NU, Ahmad M, Debray M, Yliperttula M, Declèves X. Electronic prescribing reduces prescribing error in public hospitals. J Clin Nurs 2011; 20 (21,22): 3233-3245
  • 14 Salmon J, Jiang R. E-prescribing: history, issues, potential. Online J Public Health Inform 2013; 4 (03) e10
  • 15 Ababneh MA, Al-Azzam SI, Alzoubi KH, Rababa'h AM. Medication errors in outpatient pharmacies: comparison of an electronic and a paper-based prescription system. J Pharm Health Serv Res 2020; 11: 245-248
  • 16 Johnson KB, Lehmann CU. Council on Clinical Information Technology of the American Academy of Pediatrics. Electronic prescribing in pediatrics: toward safer and more effective medication management. Paediatrics 2013; 131 (04) e1350-e1356
  • 17 Koppel R, Metlay JP, Cohen A. et al. Role of computerized physician order entry systems in facilitating medication errors. JAMA 2005; 293 (10) 1197-1203
  • 18 Berger RG, Kichak JP. Computerized physician order entry: helpful or harmful?. J Am Med Inform Assoc 2004; 11 (02) 100-103
  • 19 Qureshi NA, Al-Dossari DS, Al-Zaagi IA, Al-Bedah AM, Abudalli ANS, Koenig HG. Electronic health records, electronic prescribing and medication errors: a systematic review of literature, 2000–2014. Br J Med Med Res 2015; 5 (05) 672-704
  • 20 Desroches CM, Agarwal R, Angst CM, Fischer MA. Differences between integrated and stand-alone E-prescribing systems have implications for future use. Health Aff (Millwood) 2010; 29 (12) 2268-2277
  • 21 McMullin ST, Lonergan TP, Rynearson CS. Twelve-month drug cost savings related to use of an electronic prescribing system with integrated decision support in primary care. J Manag Care Pharm 2005; 11 (04) 322-332
  • 22 Stenner SP, Chen Q, Johnson KB. Impact of generic substitution decision support on electronic prescribing behavior. J Am Med Inform Assoc 2010; 17 (06) 681-688
  • 23 Shrank WH, Hoang T, Ettner SL. et al. The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions. Arch Intern Med 2006; 166 (03) 332-337
  • 24 Fischer MA, Vogeli C, Stedman M, Ferris T, Brookhart MA, Weissman JS. Effect of electronic prescribing with formulary decision support on medication use and cost. Arch Intern Med 2008; 168 (22) 2433-2439
  • 25 Fischer MA, Choudhry NK, Brill G. et al. Trouble getting started: predictors of primary medication nonadherence. Am J Med 2011; 124 (11) 1081.e9-1081.e22
  • 26 Ammenwerth E, Schnell-Inderst P, Machan C, Siebert U. The effect of electronic prescribing on medication errors and adverse drug events: a systematic review. J Am Med Inform Assoc 2008; 15 (05) 585-600
  • 27 Ojeleye O, Avery A, Gupta V, Boyd M. The evidence for the effectiveness of safety alerts in electronic patient medication record systems at the point of pharmacy order entry: a systematic review. BMC Med Inform Decis Mak 2013; 13 (69) 69
  • 28 Eslami S, Abu-Hanna A, de Keizer NF. Evaluation of outpatient computerized physician medication order entry systems: a systematic review. J Am Med Inform Assoc 2007; 14 (04) 400-406
  • 29 Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6 (07) e1000097
  • 30 Campbell M, McKenzie JE, Sowden A. et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 2020; 368: l6890
  • 31 Critical Appraisal Skills Programme. CASP Checklists. Accessed May 16, 2020 at:
  • 32 Liberati A, Altman DG, Tetzlaff J. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009; 6 (07) e1000100
  • 33 Furlan AD, Malmivaara A, Chou R. et al. 2015 updated method guideline for systematic reviews in the Cochrane Back and Neck Group. Spine (Phila Pa 1976) 2015; 40 (21) 1660-1673
  • 34 Higgins J, Lasserson T, Chandler J. et al. Methodological expectations of Cochrane intervention reviews (MECIR). Accessed July 28, 2021 at:
  • 35 Valentine JC, Wilson SJ, Rindskopf D. et al. Synthesizing evidence in public policy contexts. Eval Rev 2017; 41 (01) 3-26
  • 36 Campbella M, Katikireddia SV, Sowdenb A, Thomson H. Lack of transparency in reporting narrative synthesis of quantitative data: a methodological assessment of systematic review. J Clin Epidemiol 2019; 2018 (105) 1-9
  • 37 McKenzie J, Brennan S. Synthesizing and presenting findings using other methods. In: Higgins JPT, Thomas J, Chandler J. et al. eds. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed.. John Wiley & Sons; 2019: 321-348
  • 38 Popay J, Roberts H, Sowden A. et al. Guidance on the conduct of narrative synthesis in systematic reviews: a product from the ESRC methods programme. Accessed July 28, 2021 at:
  • 39 Ekedahl A, Wessling A, Melander A. Primary non-compliance with automated prescriptions transmittals from health care centers in Sweden. Res Social Adm Pharm 2002; 19: 137-140
  • 40 McCarthy G. Deliver tangible ROI. Three healthcare organizations see reduced costs, enhanced efficiency and increased compliance with CPOE systems. Health Manag Technol 2009; 30 (06) 26 28-29
  • 41 Surescripts. E-prescribing shown to improve outcomes and save healthcare system billions of dollars. 2012 . Accessed July 11, 2020 at:!content/212_eprescribing
  • 42 Andrusaitis JG. Comparison of primary compliance in electronic versus paper prescriptions prescribed from the emergency department [dissertation]. Irvine, CA: University of California, Irvine; 2017
  • 43 Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353 (05) 487-497
  • 44 Craghead RM, Wartski DM. Effect of automated prescription transmittal on number of unclaimed prescriptions. Am J Hosp Pharm 1989; 46 (02) 310-312
  • 45 Ekedahl A, Månsson N. Unclaimed prescriptions after automated prescription transmittals to pharmacies. Pharm World Sci 2004; 26 (01) 26-31
  • 46 Shrank WH, Choudhry NK, Fischer MA. et al. The epidemiology of prescriptions abandoned at the pharmacy. Ann Intern Med 2010; 153 (10) 633-640
  • 47 Fernando TJ, Nguyen DD, Baraff LJ. Effect of electronically delivered prescriptions on compliance and pharmacy wait time among emergency department patients. Acad Emerg Med 2012; 19 (01) 102-105
  • 48 Bergeron AR, Webb JR, Serper M. et al. Impact of electronic prescribing on medication use in ambulatory care. Am J Manag Care 2013; 19 (12) 1012-1017
  • 49 Pevnick JM, Li N, Asch SM, Jackevicius CA, Bell DS. Effect of electronic prescribing with formulary decision support on medication tier, copayments, and adherence. BMC Med Inform Decis Mak 2014; 14 (79) 79
  • 50 Anderson KL, Dothard EH, Huang KE, Feldman SR. Frequency of Primary Nonadherence to Acne Treatment. JAMA Dermatol 2015; 151 (06) 623-626
  • 51 Forestal DA, Klaiman TA, Peterson AM, Heller DA. Initial medication adherence in the elderly using PACE claim reversals: a pilot study. J Manag Care Spec Pharm 2016; 22 (09) 1046-1050
  • 52 Adamson AS, Suarez EA, Gorman AR. Association between method of prescribing and primary nonadherence to dermatologic medication in an urban hospital population. JAMA Dermatol 2017; 153 (01) 49-54
  • 53 Lam WY, Fresco P. Medication adherence measures: an overview. BioMed Res Int 2015; 2015: 217047
  • 54 Costantino G, Montano N, Casazza G. When should we change our clinical practice based on the results of a clinical study? The hierarchy of evidence. Intern Emerg Med 2015; 10 (06) 745-747
  • 55 Mann CJ. Observational research methods. Research design II: cohort, cross sectional, and case-control studies. Emerg Med J 2003; 20 (01) 54-60
  • 56 Fairman K, Motheral B. Evaluating medication adherence: which measure is right for your program?. J Manag Care Spec Pharm 2000; 6 (06) 499-504
  • 57 Richards KM, Shepherd MD. Claims data and drawing appropriate conclusions. J Manag Care Spec Pharm 2002; 8 (02) 152
  • 58 Brookhart MA, Patrick AR, Schneeweiss S. et al. Physician follow-up and provider continuity are associated with long-term medication adherence: a study of the dynamics of statin use. Arch Intern Med 2007; 167 (08) 847-852
  • 59 Larsen J, Stovring H, Kragstrup J, Hansen DG. Can differences in medical drug compliance between European countries be explained by social factors: analyses based on data from the European Social Survey, round 2. BMC Public Health 2009; 9 (145) 145
  • 60 Mishra P, Hansen EH, Sabroe S, Kafle KK. Socio-economic status and adherence to tuberculosis treatment: a case-control study in a district of Nepal. Int J Tuberc Lung Dis 2005; 9 (10) 1134-1139
  • 61 Goodhand JR, Kamperidis N, Sirwan B. et al. Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38 (09) 1097-1108
  • 62 Williams AB. Issue brief: medication adherence and health IT. Available at: Issue Brief: Medication Adherence and Health IT. Accessed July 28, 2021
  • 63 Bosworth HB, Granger BB, Mendys P. et al. Medication adherence: a call for action. Am Heart J 2011; 162 (03) 412-424
  • 64 Lanham A, Cochran G, Klepser D. Electronic prescriptions: opportunities and challenges for the patient and pharmacist. Adv Health Care Technol 2016; 2: 1-11
  • 65 Yeam CT, Chia S, Tan HCC, Kwan YH, Fong W, Seng JJB. A systematic review of factors affecting medication adherence among patients with osteoporosis. Osteoporos Int 2018; 29 (12) 2623-2637