Patient compliance data can be highly effective in phase 2 post hoc analyses leading up to the go/no go decision regarding a move to phase 3. Once the phase 2 objectives of assessing safety, tolerability and effectiveness have been met, the question is whether or not to proceed to phase 3 with its considerable resource requirements.
Health care providers have long known that patients are poorly compliant with recommended treatment, but the extent of non-compliance has only become apparent during the last two decades. An extensive literature now demonstrates that non-compliance is a problem in every area of health care.
Inertia is difficult to overcome. When IMC introduced the Med-ic® electronic compliance monitor (ECM) nearly a decade ago it represented the potential for a revolution in clinical trials.
Power, magnitude of treatment effect (effect size) and sample size interact to determine the signal-to-noise ratio (S/N) of a clinical trial. The object is to determine if the treatment groups differ significantly from each other.
Electronic compliance monitoring (ECM) adds cost to a clinical trial but offers enormous returns on the investment (ROI). How?
Compliance Electronic record keeping has to control for the possibility of data tampering. FDA 21 CFR Part 11 wa, s established in 1997 to govern the use of electronic records and electronic signatures.
Wireless data transmission is the key to an efficient, flexible information system. It is prerequisite to the development of increasingly comprehensive information and home care systems. Med-ic® and eCAP™ both support wireless data transmission and connectivity.
With aging population demographics combined with spiralling health-care costs, cost-reducing measures are the order of the day. Many involve systems that combine existing strategies in novel ways to give cost savings. The key to such systems is wireless interconnectivity – the ability of the various elements to intercommunicate in real-time without physical connections.
A Risk Evaluation and Mitigation Strategy (REMS) is an FDA-mandated approach to ensuring the safety of medications. The baseline for ensuring the safe use of prescribed medication is professional labelling. REMS applies to situations where professional labelling is considered inadequate to ensure the safe use of a drug or class of drugs.
The classical approach to decision-making in clinical research is the randomized trial. Patients are assigned to treatment conditions according to sample sizes that are determined a priori by power calculations. The data are not analyzed until the end of the study, at which time assignment codes are typically broken. Most clinical trials employ the Intent to Treat strategy which involves keeping all patients enrolled in the trial to its end. Positive decisions as to drug efficacy generally cannot be made until the study has been completed. Due to the cost and time involved in recruiting and processing subjects, size determination is extremely important. Unfortunately, this relies on two parameters that are rarely available during the study of new drugs – within-subject variability and the estimated magnitude of experimental effect.
"At some point, perhaps not in the far future, it will seem as wrong to run a clinical trial without compliance measurement as without randomization." B. Efron, Statistics in Medicine, 1998 (17), 249-250.
Of course we are all aware of the central role played by randomization in the clinical research process. Virtually all clinical research employs this technique. However clinicians are generally surprised to hear that the physical sciences get along quite nicely without randomization.
Clinical trial costs are spiralling out of control. Studies generally estimate the cost of bringing an Investigational new drug (IND) to market at $1B although there is considerable variability in such estimates. Data handling and pickup costs related to patient records account for a staggering 30 percent of drug development costs. This is just the beginning of the cost of non-compliance – for more details, refer to “Medication Non-Compliance”, “How Valid Are Your Clinical Trials Data?” and “Are Patient Reports Accurate?”
All research, including pharmacotherapy, may be viewed in terms of a signal to noise ratio (S/N). In administering a medication, the aim is to maximize the S/N. The signal is the desired clinical effect; the noise comprises a multitude of factors that interfere with, or obscure, the clinical effect. The clinical effect might be reduction in pain, control of seizures, reduction in white cell count, etc. Most of the myriad noise factors come under the category of 'individual differences' in response to medication. Gastrointestinal differences ranging from malabsorption to eating habits, differences in metabolism, concomitant use of alcohol and street drugs, body mass, level of activity, use of herbal remedies, and many other noise factors conspire to obscure the therapeutic effect (signal).
The problem of having patients determine their own dosing during clinical trials is widely recognized. If data obtained in clinical trials where patients take medication once or twice a day are known to be inaccurate, it follows that data from patients taking medication intermittently over longer intervals will be even less accurate. Such studies generally rely on the patient recording the date and time of self-medication.
It is widely accepted that patients participating in clinical trials are less than perfectly compliant with their medication regimens. The extent to which non-compliance affects the results of clinical trials is unknown. Several factors mitigate against the assessment of this phenomenon, principal of which is the lack of a methodology to monitor patient compliance in a non-invasive (ie: unbiased) way.
Health care providers have long known that patients are poorly compliant with recommended treatment. The extent of non-compliance has only become apparent during the last two decades. An extensive literature now demonstrates that non-compliance is a problem in every area of health care. Many non-compliance issues are in the area of clinical pharmacy. With rapid advances in the understanding of the biological bases of medical and psychiatric disorders, pharmacotherapy has become by far the predominant therapeutic approach.