Introduction
Clinical trials in essence attempt to establish evidence for interventions at the clinical level for better outcomes to patients. Many of such clinical trials compare existing interventions to newer interventions or compare interventions to no interventions at all. Such studies attempt to not only establish the utility of the intervention it also attempts to study the patient safety aspects of the interventions.
Compliance as a Critical Element in Clinical Trials
Quite often clinical trials involve the evaluation of medications. Compliance, which is measured as a percentage, may be taken as “the extent to which a patient acts in accordance with the prescribed interval and dose of dosing regimen” (Cramer et al, 2007). Clinical trials of medications and interventions measure not only the efficacy of the intervention but also the safety of the interventions. Poor compliance is a significant factor that affects the efficacy and safety of the intervention (ICH Harmonised Tripartite Guideline, 2000). Adverse drug reactions have to be reported (ICH Harmonised Tripartite Guideline, 1994). Poor compliance affects the understanding of adverse reactions and under-reporting of adverse drug reactions.
Considerations of Compliance in Clinical Trials
The findings of clinical trials with particular emphasis on the benefits and risks of the intervention hinge on compliance with the intervention, especially in the case of medication trials. Human behaviour is such that in the beginning subjects may demonstrate compliance, but may not continue to persist with such compliance (Cramer et al, 2007). Persistence in compliance may tend to disappear from small issues like the pill to be consumed being too large or the timings of taking the medication being too frequent or inconvenient. There is also the issue of forgetfulness impinging on the correct reporting compliance, particular when the clinical trial involves medication interventions at home (Lee et al, 2007).
Given that compliance is a major issue in clinical trials then subjects must be encouraged to comply. Designing the packaging of the medications used in the clinical trial must be such that it makes it easy for the patient to comply, like in smaller tablets for ease in consumption (Lamb, 2004). Monitoring does help in evaluating compliance, it has a limited impact on compliance. Compliance is better achieved by encouraging the patients to comply, by making it easy ion them to use the interventions in a timely and complete manner and by making them understand the possible benefits that will accrue from complying with the regimen (Baros et al, 2007). Despite the best efforts to encourage compliance, it is virtually impossible to ensure total compliance and taking into consideration the impact that non-compliance could have on the findings and the veracity of these findings non-compliance has to be measured strictly and systematically across the whole gamut of the clinical trial (Gareen, 2007). Measuring compliance in clinical trials is not easy and poses a challenge to the study. Overcoming this challenge involves the use of appropriate statistical methods like the Maximum Penalized Marginal Likelihood, which provides good performance even when there is limited compliance data and its key assumptions cannot be met (Kenner & Sheiner, 2004).
Conclusion
Poor compliance can mar the veracity of the results in clinical trials and through that give false risks and benefits findings. Monitoring is not a solution and instead subjects need to be encouraged to comply with intervention requirements. Despite the best efforts there remains the possibility of poor compliance and it is the use of robust statistical programs that provide a solution in such cases.
Literary References
Baros, A. M., Latham, P. K., Moak, D. H., Voronin, K & Anton, R. F. 2007, What role does measuring medication compliance play in evaluating the efficacy of naltrexone?’ Alcoholism, clinical and experimental research, vol.31, no.4, pp.596-603.
Cramer, J. A., Roy, A., Burrell, A., Fairchild, C. J., Fuldeore, M.J., Ollendorf, D.A., & Wong, P. K. 2007,’ Medication Compliance and Persistence: Terminology and Definitions’, International Society for Pharmacoeconomics and Outcomes Research.
Gareen, I. F. 2007, ‘Noncompliance in cancer screening trials’, Clinical trials, vol.4, no.4, pp.341-349.
ICH Harmonised Tripartite Guideline. 1994, ‘Clinical Safety Data Management: Definitions and Standards for Expedited Reporting’, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
ICH Harmonised Tripartite Guideline. 2000, ‘Choice of Control Group and Related Issues in Clinical Trials’, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Web.
Kenner, L. A. & Sheiner, L. B. 2004, ‘Estimating treatment effect in the presence of non-compliance measured with error: precision and robustness of data analysis methods’, Statistics in medicine, vol.23, no.23, pp.3561-3580.
Lamb, M. 2004, ‘Improving Patient Compliance in Clinical Trials: Smart Packages or Smart Design?’ Pharmaceutical Manufacturing and Packing. Web.
Lee, K. J., Grace, K. A., Foster, T. G., Crawley, M. J., Erowele, G. I., Sun, H. J., Turner, P. T., Sullenberg, L. E. & Taylor, A. J. 2007, ‘How should we measure medication adherence in clinical trials and practice?’ Therapeutics and Clinical Risk Management, vol.3, no.4, pp.685-690.