*NonCompliance

(3)

• *Defined as failure to self-administer prescribed medicines according to the instructions given by the doctor and codified in a prescription. 
• Noncompliance can be either intentional or unintentional.  
• In either case, noncompliance is associated with poorer clinical results than compliance.

The cost of noncompliance

(2)

• The cost of noncompliance is extraordinarily high.  
• It has been estimated that more than $15,000,000,000 per year is spent to treat the medical results of failure to appropriately self-administer prescription drugs.

• Use right drug in the 
• prescribed dosage 
• by correct route 
• at the proper times 
• for the correct duration.  
• *Conclusion: 
• *Five Drug Related Decisions Need to be Made Every Time a Medicine is Taken

Compliance

Filling

(2)

• The most obvious form of noncompliance is the failure to ever fill prescriptions (20%).  
• In addition, 30% of those that are filled initially are not properly refilled.

The frequency of noncompliance

(7)

• *Very Hard to accurately estimate; Variously set at 10-95%
• Most studies suggest that the frequency is around 70%
• 7 year UGDP study: 74% changed drug handling without consulting a physician
• *The Frequency of noncompliance has been variously estimated between 10% and 95% with a median of about two thirds (66%) of patients.  
• In one major study, 74% of the patients were found to have altered the handling of their medication without consulting a physician!
• Such studies demonstrate that most/all patients are non-compliant to some degree.  
• Furthermore, their degree of non-compliance has been shown to vary with factors such as health and age.

The frequency of noncompliance

Best Assesment Method: Direct Observation?

• Direct observation is arguably the best way to determine the frequency of noncompliance but it is usually impractical and is rarely used.  
• In addition, direct observation might overestimate compliance because the patients would know that they were being watched.

*What Conclusions Can We Reach Regarding Noncompliance?

(5)

• *Most or all patients are noncompliant to some extent
• *Their degree of noncompliance will vary with;
• Intellect 
• Health and 
• Age

Factors Which Encourage Pt Compliance

(5)

• Keep it simple (KISS)!
• *Once-per-day regimens are best
• *Multiple doses are an enormous problem, esp. for the elderly and/or sick
• Make it personal
• Develop a personal relationship & frequency falls from 45% to 17%

• 15 doses from 13 bottles at 4 different times/day
• 15 x 5 = 75 drug decisions/day

*Patient Education Must Include

(10)

• What are the drug’s benefits?
• How will tx be monitored?
• Consequences of noncompliance?
• Side effects & drug interactions?
• Will the pt become “addicted”?
• Rx Parameters:
• How (what route)?
• How much?
• How long?
• *Your goal should be to encourage your patients to "partner" with you in managing their health care

*Other Factors Which Discourage Patient Compliance

(12)

• Lack of discernible progress
• Taste
• Cost
• Poor past Rx experiences
• Peer pressure
• Special patient factors
• Intellect:
• Confusion
• Inability to understand instructions
• Difficulty remembering to take meds
• Poor eyesight/inability to read
• Dependence on others (children & elderly)

How Can One Best Assess Compliance?

(6)

• PHYSICIAN’S ESTIMATION
• PATIENT’S REPORTS
• Strep throat study
• PILL COUNTING
• MEDICATION MONITORS
• DIRECT MEASUREMENT

*Effects of Noncompliance

(4)

• *IT MIGHT JEOPARDIZE THERAPY.
• *  THE DOCTOR MIGHT BE MISLED.
• *  DRUG TOXICITIES CAN RESULT FROM NONCOMPLIANCE IF DRUGS HAVE SMALL TIs
• Noncompliance must always be considered a possible cause of therapeutic failure

Placebos and the Placebo Effect

(4)

• Placebo = Latin verb = ‘I shall please’
• *A placebo is a drug/agent that lacks therapeutic effect and is merely given to please the patient.
• Placebos have been used since the beginning of medicine by witch doctors, medicine men, and apothecaries who had little else to sell.

How Does a Placebo Work?

(3)

• It works in the CNS by calming a patient’s anxieties & reducing pain.
• In cases involving pain, placebo effects have been shown to be blockable by naloxone so they must be due to release of endorphins.
• Patterns of brain activity (right) show that placebos can produce  changes in brain activity

How Powerful is the Placebo

(3)

• Dr. Beecher and WWII; a battlefield surgeon who treated severely injured soldiers
• *35% of patients respond positively to placebo Rx for conditions from postoperative wound pain to angina to the common cold.
• *20-25% respond positively to asthma, hyper-tension, & depression.

*Placebo Reactors

(4)

• *They are individuals who obtain positive responses from use of a placebo.
• *They cannot be identified in advance by psychological testing but can be by drug trials.
• *Depending on current emotional state, every individual is potentially a placebo reactor
• *Medical student study (30% responders)

*"Toxicities" Resulting from Use of Placebos

(5)

• It can destroy your relationship with the patient.
• It can convince a sick patient that he/she is being adequately treated.
• It can convince a well patient that he/she is sick.
• It may promote psychological addiction
• It might serve as a physician’s crutch.

*Possible Effects of Noncompliance on Clinical Trials

(3)

• If unequally distributed, it can cause either false positives or false negatives.
• It can diminish test sensitivity even if NCs are uniformly distributed
• The presence of unrecognized NCs in the treatment group will cause underestimation of a drug’s toxicity

Summary: Noncompliance and Testing

(5)

• *Monitoring compliance during clinical trials should be mandatory.
• *Noncompliers can be partially or completely eliminated by use of a pretrial exclusionary test.
• VA Cooperative Hypertension Study
• Riboflavin tablets were used and the ingredient was measured in urine.
• Insufficiently compliant patients (ca 50%) were eliminated prior to the real test.

*Placebos and Clinical Testing

(6)

• Used to account for the tendency of a patient to respond positively to any new treatment even if inactive (i.e., the placebo effect).
• Used to take into account the fact that severity of a disease waxes and wanes irrespective of the use of drug or placebo.
• New drugs are generally compared to (a) placebos and (b) a known effective drug but, if an illness is serious, it would not be ethical to test against a placebo.
• Control for the placebo effect can only be achieved if the drug is administered under double-blind conditions. 
• How important is the use of double-blind procedure?
• Elimination of placebo responders from treatment groups  is possible by pretrial testing & often makes results clearer.