Small companies and academics often wish to enter into arrangements with larger pharmaceutical companies. These agreements can be difficult to work out, and may ultimately depend on the risk-benefit equation for the larger partner. In addition to financial risk, companies consider risks relating to obtaining regulatory approvals, clarity of intellectual property, suitability of manufacturing at large scale, clear data on safety and efficacy, and overall corporate strategies regarding the expected market. The equation changes as product development proceeds, risks decrease, and value increases. The most successful arrangements often occur during early clinical trials. Negotiating agreements is time-consuming and complicated. If experienced, in-house expertise is not available, employing outside consultants may lead to more advantageous outcomes. Financial issues can be particularly challenging in developing drugs for special populations, tropical diseases and orphan diseases because of perceived limited market value.