**The reproductive performance**

These are measurements intended to determine the effects of the drug agents on; mating behaviour, reproduction, parturition, progeny birth defects, and postnatal development.

metabolism of the candidate drug compound. The effects of the drug as a function of dosage are established in a small number 25 – 50 of healthy volunteers. When the drug is expected to have significant toxicity, as often the case with cancer and AIDS therapy, volunteer patients with the disease are used instead of the healthy volunteers. The re‐

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**iii.** Meaningful and sensitive indices for drug effects must be used i.e. well defined end-

**iv.** The experimental observations must be converted to data and then into valid

**v.** The accuracy of diagnosis and severity of the disease must be comparable between

**vi.** The dosages of the drugs must be chosen and individualized in a manner that allows

**vii.** Compliance with experimental regimens should be assessed before subjects are

estimates of the true potential benefits or toxicity of a particular treatment.

**viii.** Ethical considerations. These may be the major determinants of the types of controls

For clinical trials to have validity they must be based on a sound statistical basis. Some of the

Randomization is a design which ensures that there is no bias in allocation of treatments among the different groups. The purpose of randomization is to minimize the possibility that an observed treatment effect is due to inherent differences between groups. Randomization eliminates bias by avoiding recruiting patients who have a particular characteristic to one group and not the other e.g. only women/men and smokers/alcoholics. Randomization should not be carried out until immediately before treatment. The delay allows a patient to have second thoughts about taking part or the investigator to have to re-consider about admitting patients to the study. Simple methods of randomization can be designed using published tables of random numbers, where treatments are in a form of a square in which each treatment is

assigned to experimental or control groups. Non-compliance may cause false

that can be used e.g. for therapeutic trials that involve life threatening diseases for which there is already in-effective therapy, the use of a placebo is considered unethical. In such cases, new treatments must be compared with standard therapies.

points such as survival or pain relief should be used rather than surrogate or intermediate markers e.g. levels of enzymes involved in the process of survival/pain

quirements of clinical trials include the following:

relief.

conclusions.

**14.2. Study design of phase I trials**

**Randomization**

of the criteria that must be met include;

the groups being contrasted.

**i.** Homogenous populations of patients must be selected.

**ii.** Appropriate controls for the investigation must be included.

relative efficacy to be compared at equivalent toxicities.

#### **Carcinogenicity studies**

These studies are required to determine the effects of prolonged usage of the drug under investigation. They involve hematological and histological autopsy analysis.

#### **Mutagenicity studies**

These studies look at the genetic stability and mutations of bacterial or mammalian cells in culture. These studies are at the academic research level and are intended to provide data for future research.

#### **Investigative toxicology**

The main purpose of toxicology is to discover the pathways that are involved in toxic action. It includes studies on mechanisms of toxic action of drugs which may lead to the development of safer drugs.
