Posc309 A Pragmatic Patient Finding Methodology In The Ultra Rare

Leo Migdal
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posc309 a pragmatic patient finding methodology in the ultra rare

Part 1 of this series provided an overview of rare diseases and the special challenges they present to biopharmaceutical companies. In this installment, we explore one of the most basic—and most confounding—of those challenges: Finding patients. In the European Union, a disease is considered rare when it affects fewer than five in 10,000 people. In the United States, a disease is defined as rare when it affects fewer than seven in 10,000 people.1 Some diseases are far rarer. Huntington’s disease, for example, only affects 3 to 7 per 100,000 people of European ancestry (and is even less common in other populations).2 And, compared to some other ultra-rare diseases, Huntington’s disease could seem... As one would expect, rare diseases mean rare—and typically geographically dispersed—patients.

That makes them hard to identify, and this presents significant problems for three key stakeholder groups: The patients themselves, the physicians who treat them, and the pharmaceutical companies that are working to develop new... The “typical” rare disease patient faces a range of obstacles before ever getting a proper diagnosis. Often, primary care physicians have limited (or no) familiarity with the patient’s condition, and refer the patient to a specialist after being unable to determine the cause of the patient’s symptoms. Unfortunately, the patient’s journey usually does not end with the specialist. Depending on the disease, awareness among specialists can be similarly limited, and patients will often see multiple doctors on their journey to a diagnosis. It can take numerous doctors and multiple misdiagnoses and hence, a long period of time before the correct rare disease is identified.3

Forty years after the initial instatement of the US Orphan Drug Act, awareness of rare diseases, as well as the number of available treatments has increased significantly. Despite this positive trend, however, over 90% of rare diseases still lack effective treatments, a situation exacerbated by the challenges drug developers face when trying to bring novel treatments to rare disease patients1. A significant challenge within the rare disease field is finding patients who could benefit from a specific treatment. While it might be assumed that the unmet needs of a rare disease would automatically drive demand for a novel therapeutic—whether for participation in clinical trial or for access to newly approved drugs—the reality... In fact, matching patients with treatments can become a literal search for a needle in a haystack for drug developers. The time to diagnosis is for rare diseases typically long, averaging 4.7 years2.

Time to diagnosis can be even longer for many patients, with physicians often struggling to piece together the complex puzzle of signs and symptoms that indicate a rare disease. This can result in low diagnostic accuracy, with around three-thirds of patients being misdiagnosed at least once2. Rare diseases exist on a spectrum, ranging from the easily detectable to the elusive (Figure 1). Rare diseases that are relatively easy to recognise, such as Heamophilia3, typically have high disease awareness and a well-understood pathophysiology that allows for clear symptom description. For monogenic disorders, family history and distinct phenotypic features can often aid in the recognition of the disease. In the best-case scenario, such rare diseases also have clear diagnostic tests, making them identifiable.

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(:1G1,*Fe>kK=m?#n_liMAY=0G27IZdhZ34kgu,S7LTIiTP'E5@i']ooth_nU6CAX YXUH0??9h<&Jt>/ZSp P7C1A]i3gf#na\G^".'TPMgSg/N=(s*Cko*j^UmJJ[?DQ\f9%DpIq<.:2O:M7'mn' UXte#CtN_^dj$74QDsWA^,+7Fh0"jT>DAoZEJ,ZqOW+VIO-%k*pm[@Mr^\8;EO6NP 51]f=*)0ICBH,-\6n_^?UoB&:`6g$;!t*c@.!Qc`T\ouI%P`k!D2JW>MZL`S/>C56 \96k8$?:_U+Mj'L]u;[[1e@&Yk"-;V-+ekO:I'\s!]N4E8l/[k_UgN c=MaJHF0h_ZT(8u)<1uu-(EG$*4bD?Q8fsGCPRJO)E"@a*$UUKW#df:7ge)Q,_O.T #PaqIbus`J!F$a)b@FMqjLS&*H#9Ds"=qpH$+?p*[oMl4SjP?R;90/.E"g:]*4i&b D@l(.Oh6EN-GCM]T/7!A?K]sY_2qgOUUcr?3s.]W."c4#FX&tC]qPC;/.L-ffm&a[ 7tD\_)Udo`TiE)_X4)?SCc)^.G^mnN)Ne[rotqtW^";q>SL,79K4s8#Q"K><$'$2s Qe?^kH)N0)W2Dfk7tI@.4Z[7Z6ZkZ$O]3;8^LPR]I[k2uMo(f[b:+$19RFG"`5'^LqTb3EHm[`.FQ1)6s .=Umr;.brSr'"EeiRW-0na3A'c&bP(]7fdE]I#"=j66)T-V'90r`^i8^QdMtd_@6M =;$KoBt1K?m)kq$!)o?J7f~> endstream endobj 5 0 obj <> endobj 6 0 obj <>stream 2021-11-05T10:37:12Z 2021-11-05T10:37:16Z 2021-11-05T10:37:16Z Adobe InDesign 16.4 (Windows) uuid:af303dd4-9d09-4803-b1d3-6d8766a3adcf xmp.did:2f80f79b-9f66-b049-a490-56eddc41a3bb xmp.id:96922b17-d42b-8a46-afd5-b6978909d9d7... While we have seen a significant increase in the number of drugs for rare diseases, accurate diagnosis rates of rare diseases continue to trail behind those of more prevalent diseases. The average time to diagnosis for a patient with a rare disease is 5 to 7 years. The delay is driven by: In response to this delay, companies have invested in disease awareness and diagnosis programs, including artificial intelligence (AI)-driven patient-finding initiatives. While heralded as the solution to address the diagnosis lag, results from these programs have been mixed and are the source of several challenges, including:

At 81qd, we take a unique approach by leveraging AI to identify specific physician practices where undiagnosed patients with the highest probability of having a rare condition are currently being managed for other conditions. Over the years, we have partnered with many companies to help them overcome the challenges with their patient-finding initiatives. To guide our clients forward, we offer a simple framework based on the popular icebreaker game: Be prepared to be surprised. Undiagnosed patients identified through AI-driven approaches will frequently not look like diagnosed patients. If they did, and if they were that simple to find, why would we need AI?

Because most marketers are guilty of confirmation bias, they often look for attributes that confirm their preexisting knowledge about the market or a disease. When they see something contrary to their experience, they naturally refute it. AI should be designed to identify patients that may not look like “typical patients.” However, the inherent heterogeneity of the patient journey experienced by those with rare diseases means there are no “typical patients.”...

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Part 1 of this series provided an overview of rare diseases and the special challenges they present to biopharmaceutical companies. In this installment, we explore one of the most basic—and most confounding—of those challenges: Finding patients. In the European Union, a disease is considered rare when it affects fewer than five in 10,000 people. In the United States, a disease is defined as rare w...

That Makes Them Hard To Identify, And This Presents Significant

That makes them hard to identify, and this presents significant problems for three key stakeholder groups: The patients themselves, the physicians who treat them, and the pharmaceutical companies that are working to develop new... The “typical” rare disease patient faces a range of obstacles before ever getting a proper diagnosis. Often, primary care physicians have limited (or no) familiarity wit...

Forty Years After The Initial Instatement Of The US Orphan

Forty years after the initial instatement of the US Orphan Drug Act, awareness of rare diseases, as well as the number of available treatments has increased significantly. Despite this positive trend, however, over 90% of rare diseases still lack effective treatments, a situation exacerbated by the challenges drug developers face when trying to bring novel treatments to rare disease patients1. A s...

Time To Diagnosis Can Be Even Longer For Many Patients,

Time to diagnosis can be even longer for many patients, with physicians often struggling to piece together the complex puzzle of signs and symptoms that indicate a rare disease. This can result in low diagnostic accuracy, with around three-thirds of patients being misdiagnosed at least once2. Rare diseases exist on a spectrum, ranging from the easily detectable to the elusive (Figure 1). Rare dise...

These Tests Can Be Based On Genetic Markers, Such As

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