Request for Proposals (RFP) Executive Summary

Problem

Problem Statement

To determine whether EEG and evoked potential biomarkers for neurology, psychiatry, pain or urogenital indications can be used in either healthy volunteers and/or patient populations to demonstrate centrally mediated pharmacological activity and to provide evidence of early efficacy.

In order to improve confidence in the activity of exploratory CNS drugs, it is critical to establish centrally mediated pharmacodynamic activity in humans. In the absence of a PET ligand or clearly linked physiological response, the demonstration of central binding and subsequent activity is particularly challenging. Pfizer research has invested substantially in the use of spontaneous EEG, evoked potential and sleep endpoints as a means to assess central pharmacology. However, the ability to translate these endpoints to healthy volunteer or small Phase IIa patient studies remains unclear. In addition, because of the lack of well-developed pharmacology biomarkers suitable for a healthy volunteer population, the learning extracted from Phase 1 studies with respect to PK/PD properties of compounds and mechanisms is usually limited. As a result, drugs progressing through the pipeline enter late stage development with a less-than-optimal pharmacological knowledge. Furthermore, the opportunities to improve upon a backup candidate's profile based on rapid learning from the clinic is limited.

It has been demonstrated for various central mechanisms (for example opiate receptor agonists, stimulants and GABA receptor modulators) that exposure-EEG response data in healthy volunteers may provide early signposts of potential issues with respect to time course of effect (i.e. required exposure levels for efficacy, onset, offset, toleration, active metabolites), which can subsequently be managed in a more proactive and rapid manner than currently is the case. In addition, various evoked potential paradigms such as miss-matched negativity in schizophrenics, cognitive dysfunction in early Alzheimer’s disease or EEG paradigms of urinary incontinence, may serve as useful tools to assess efficacy in humans where preclinical models are less than optimal.

Key Requirements for Successful RFP Bidders

1. Do you have access to relevant patient populations for the model under question and can you obtain IRB approval, recruit and complete studies of approximately 10 – 20 patients within a six month – one year time frame?
2. Do you have established expertise in the model as evidence by publication in peer reviewed journals or by internal reports that you are willing to share with Pfizer?
3. Do you have experience working with investigational drugs?
4. Can you design a research program that addresses this problem?

1. Expertise required to solve problem:

1. Providers must have proven expertise, strategies or methodologies that will differentiate central pharmacological effects from peripheral effects with a central EEG signature.
2. Providers must have proven expertise in assessing central pharmacological effects using spontaneous spectral band EEG (e.g. eyes open/eyes closed assessment on cortical quantitative EEG activity), sleep endpoints (e.g. REM onset/latency etc) and evoked potential endpoints (e.g. P50, P300 etc).
3. Providers must have proven experience with 19 and 64 channels (or greater) and have knowledge of topographic analysis via such programs as  LORETA or ELECTRA.
4. Providers must have experience with either Morpheus or Somnologica software.
5. Providers must be willing to commit to at least 1 validation study each to establish utility of evoked potential paradigms in addition to 3 – 4 Phase I/IIa drug studies in HVs  and/or patients at Pfizer sponsored centers.

2. Resources required to solve problem

1. Providers must have portable units (e.g. neurobit lite) that can be utilized in both vendor sponsored or Pfizer sponsored PhI units.
2. Providers must have currently employed technical experts who will provide support (or be responsible for) creation of a research plan, site initiations, data collection, data analysis, data reports and site training.
3. Providers must be willing to provide all raw unprocessed data.

3. Geographic Requirements

1. Providers must be able to provide service at Pfizer CRU locations (US, Brussels, Singapore) or conduct in house at comparable or less cost than Pfizer internal costs.

Deliverables

Targeted use of evoked responses in healthy volunteers and/or patients in PhI/IIa clinical trials as validated evidence of dose-dependent, centrally mediated pharmacological activity (POM) and as a tool to for dose determination.

Time to Solve the Problem

The estimated timeframe is within 3 years. Please provide a best estimate of time in the proposal.

Request for Proposal (RFP) Due Date

All final proposals must be submitted no later than August 31, 2007.

Submitting a Proposal

If you are interested in submitting a proposal to address the above therapeutic area topic, please complete the following informational template and send it to: [email protected]

• Neurosciences - RFI (PDF)