Over the past forty years, the 4Ps in medicine: personalized, predictive, preventive, and participatory have been revolutionizing the nature of healthcare, moving it from a reactive model of when a patient is already ill to a preventive model of wellness. There are no less than 90 citations in Pub Med of publications addressing implementation of the 4Ps in a variety of medical disciplines from inflammatory bowel disease¹, rotator cuff tears², and breast cancer prevention³. The same 4P-medicine concepts now show promise in the treatment of chronic diseases such as cardiovascular disease, cancer, respiratory diseases and type-2-diabetes which are the costly leading causes of death, disability and diminished quality of life.⁴

The 4 Ps are new systems approaches that will catalyze personalized medicine — a medicine that focuses on an integrated diagnosis, treatment, and prevention of disease in individual patients.

The concepts were first introduced by pioneer French immunologist Jean Dausset. Jean Dausset, born in 1916 in Toulouse, France, shared shortly before his death at age 92, that he wanted to be remembered for his contributions to anthropology, the immune response, transplantation and predictive medicine through personalized disease prevention⁵. All were based on his fundamental discovery of the HLA system, now defined as the "leucocyte-platelet and tissue system" or the "human major histocompatibility complex" in the 1950s. In establishing the important role of the histocompatibility antigens in the control of the immune response and in the susceptibility or resistance to a wide variety of diseases, Dausset and his colleagues realized that they had defined a key element of the biologically unique identities of individuals, the histocompatibility complex (MHC), in which the genes encoding the HLA antigens were located. This meant that disease susceptibility could be tracked through populations. For their discovery Dausset, together with fellow scientists Baruj Benacerraf and George Davis Snell, was awarded the prestigious Nobel Prize for Physiology or Medicine in 1980.

Also, in recognition of Professor Dausset as one of the first researchers to have understood the enormous ethical consequences of biomedicine, and the fundamental importance of dialogue between scientists and the public, Pope John Paul II received him in a private audience in 1985⁵.

In 2008, Leroy E. Hood and David J. Galas (Institute for Systems Biology Battelle Memorial Institute) wrote that implementation of the 4Ps will:

• “Detect disease at an earlier stage, when it is easier and less expensive to treat effectively.
• Stratify patients into groups that enable the selection of optimal therapy.
• Reduce adverse drug reactions by more effective early assessment of individual drug responses.
• Improve the selection of new biochemical targets for drug discovery.
• Reduce the time, cost, and failure rate of clinical trials for new therapies.
• Shift the emphasis in medicine from reaction to prevention and from disease to wellness⁶.

Moreover, they continue, “P4 medicine promises to sharply reverse the ever-escalating costs of healthcare – introducing diagnosis to stratify patients and disease, less expensive approaches to drug discovery, preventive medicine and wellness, and exponentially cost-decreasing measurement technologies. P4 medicine also promises to improve patient outcomes, and to empower both the patient and the physician. Having much more, and more accurate, information to be used by the patient and the doctor to make decisions about prevention and treatment is at the heart of this future medicine.⁶”

In 2020, F Kojima of the Department of Thoracic Surgery, St. Luke's International Hospital, Tokyo, embraced the 4Ps concepts for surgery. He wrote that “successful achievements in the arena of thoracic surgery are fully appreciated from the perspective of these concepts” including precise assessment of target lesion, data-based preventive risk assessment, minimally invasive approach, clinical pathways for enhanced recovery, and personalized outpatient follow-up. These new health technologies require assessment based on patient-reported outcomes in addition to the traditionally acknowledged endpoints of surgery: curability, mortality, or morbidity.⁷

The future is now as the 4Ps, first introduced forty years ago by Professor Jean Dausset, move medicine from reactive care of the already ill to preventive wellness for all.

References:

1. Lenti MV, Scribano ML, Biancone L, Ciccocioppo R, Pugliese D, Pastorelli L, Fiorino G, Savarino E, Caprioli FA, Ardizzone S, Fantini MC, Tontini GE, Orlando A, Sampietro GM, Sturniolo GC, Monteleone G, Vecchi M, Kohn A, Daperno M, D'Incà R, Corazza GR, Di Sabatino A. Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease. Front Med (Lausanne). 2023 Apr 11;10:1031998.
2. Longo UG, Carnevale A, Massaroni C, Lo Presti D, Berton A, Candela V, Schena E, Denaro V. Personalized, Predictive, Participatory, Precision, and Preventive (P5) Medicine in Rotator Cuff Tears. J Pers Med. 2021 Apr 1;11(4):255.
3. Jordan VC. The 4Ps of Breast Cancer Chemoprevention: Putting Proven Principles into Practice. Cancer Prev Res (Phila). 2017 Apr;10(4):219-222..
4. Sagner M, McNeil A, Puska P, Auffray C, Price ND, Hood L, Lavie CJ, Han ZG, Chen Z, Brahmachari SK, McEwen BS, Soares MB, Balling R, Epel E, Arena R.Prog Cardiovasc Dis. 2017 Mar-Apr;59(5):506-521.
5. Auffray C, Charron D, Hood L. Predictive, preventive, personalized and participatory medicine: back to the future. Genome Med. 2010 Aug 26;2(8):57.
6. Hood L. Galas D. (2008). P4 Medicine: Personalized, Predictive, Preventive, Participatory: A Change of View that Changes Everything: A white paper prepared for the Computing Community Consortium committee of the Computing Research Association. http://cra.org/ccc/resources/ccc-led-whitepapers/
7. Kojima F. [Precision Surgery, Patient Reported Outcome, and Participatory Medicine]. Kyobu Geka. 2020 Apr;73(4):244-249. Japanese. PMID: 32393682.