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Background Minimising prescription costs while maintaining quality is a core element of delivering high value healthcare. There are various strategies to achieve savings, but almost no research to date on determining the most effective approach. We describe a new method of identifying potential savings due to large national variations in drug cost, including variation in generic drug cost; and compare these with potential savings from an established method (generic prescribing). Methods We used English NHS Digital prescribing data, from October 2015 to September 2016. Potential cost savings were calculated by determining the price-per-unit (e.g. pill, ml) for each drug and dose within each general practice. This was compared against the same cost for the practice at the lowest cost decile, to determine achievable savings. We compared these price-per-unit savings to the savings possible from generic switching; and determined the chemicals with the highest savings nationally. A senior pharmacist manually assessed whether a random sample of savings were practically achievable. Results We identified a theoretical maximum of £410M of savings over 12 months. £273M of these savings were for individual prescribing changes worth over £50 per practice per month; this compares favorably with generic switching, where only £35M of achievable savings were identified. The biggest savings nationally were on glucose blood testing reagents (£12M), fluticasone propionate (£9M) and venlafaxine (£8M). Approximately half of all savings were deemed practically achievable. Discussion We have developed a new method to identify and enable large potential cost savings within NHS community prescribing. Given the current pressures on the NHS, it is vital that these potential savings are realised. Our tool enabling doctors to achieve these savings is now launched in pilot form. However savings could potentially be achieved more simply through national policy change. Abbreviations BNF British National Formulary CCG Clinical Commissioning Group GP General Practice MR Modified Release NHS National Health Service NIC Net Ingredient Cost NP8 Non-Part VIII, i.e. drugs not listed in Part VIII of the Drug Tariff PPU Price-Per-Unit

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